Publications by authors named "Vinit Raj"

30 Publications

  • Page 1 of 1

Synthesis of pH-sensitive crosslinked guar gum-g-poly(acrylic acid-co-acrylonitrile) for the delivery of thymoquinone against inflammation.

Int J Biol Macromol 2021 May 12;182:1218-1228. Epub 2021 May 12.

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (A Central University), VidyaVihar, Raebareli Road, Lucknow, U.P. 226025, India. Electronic address:

The present work aims to synthesize the pH-sensitive crosslinked guar gum-g-poly(acrylic acid-co-acrylonitrile) [guar-g-(AA-co-ACN)] via microwave-assisted technique for the sustained release of thymoquinone. The synthesized material [guar-g-(AA-co-ACN)] was optimized by varying synthetic parameters viz. monomer concentration, reaction time, and microwave power to obtain the maximum yield of the crosslinked guar gum grafted product as well as maximum encapsulation of thymoquinone. The synthesized material [guar-g-poly(AA-co-ACN)] was characterized by FT-IR, SEM, XRD, NMR, zeta potential, and thermal techniques. This synthesized material was used to encapsulate thymoquinone (TQ) for effective nanotherapeutic delivery. In-vitro thymoquinone release behavior of guar-g-poly(AA-co-ACN) based nanoparticles (NpTGG) was investigated. The maximum thymoquinone release (78%) was achieved at pH 7.4 and time (6 h). The NpTGG also exhibited better antioxidant activity and hemocompatibility as compared to thymoquinone. Cytotoxicity of uar-g-(AA-co-ACN) and NpTGG was also evaluated against the human kidney VERO cell line and found to be nontoxic. Current research provides a cost-effective and green approach for the synthesis of guar-g-(AA-co-ACN) and NpTGG for sustained release of thymoquinone.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.072DOI Listing
May 2021

Deciphering the Relationship Between Cycloheximides Structures and Their Different Biological Activities.

Front Microbiol 2021 7;12:644853. Epub 2021 Apr 7.

Department of Agricultural Chemistry, College of Agriculture and Life Science, Institute of Environmentally Friendly Agriculture, Chonnam National University, Gwangju, South Korea.

species are the most important sources of antibacterial, antifungal, and phytotoxic metabolites. In this study, cycloheximide (CH) and acetoxycycloheximide (ACH) were isolated from the fermentation broth of sp. JCK-6092. The antifungal and phytotoxic activities of the two compounds (CH and ACH) and a cycloheximide derivative, hydroxycycloheximide (HCH), were compared. CH exhibited the strongest antagonistic activity against all the true fungi tested, followed by ACH and HCH. However, both CH and ACH displayed similar mycelial growth inhibitory activities against several phytopathogenic oomycetes, and both were more active than that of HCH. Disparate to antifungal ability, ACH showed the strongest phytotoxic activity against weeds and crops, followed by HCH and CH. ACH caused chlorophyll content loss, leaf electrolytic leakage, and lipid peroxidation in a dose-dependent manner. Its phytotoxicity was stronger than that of glufosinate-ammonium but weaker than that of paraquat in the experiments. CH and its derivatives are well-known protein synthesis inhibitors; however, the precise differences between their mechanism of action remain undiscovered. A computational study revealed effects of CHs on the protein synthesis of (oomycetes), (true fungus), and (plant) and deciphered the differences in their biological activities on different targets. The binding energies and conformation stabilities of each chemical molecule correlated with their biological activities. Thus, molecular docking study supported the experimental results. This is the first comparative study to suggest the ribosomal protein alteration mechanisms of CHs in plants and fungi and to thus show how the protein inhibitory activities of the different derivatives are altered using molecular docking. The correlation of structures features of CHs in respect to bond formation with desired protein was revealed by density functional theory. Overall collective results suggested that CHs can be used as lead molecules in the development of more potent fungicides and herbicides molecules.
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http://dx.doi.org/10.3389/fmicb.2021.644853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058199PMC
April 2021

Recent findings and future directions of grafted gum karaya polysaccharides and their various applications: A review.

Carbohydr Polym 2021 Apr 23;258:117687. Epub 2021 Jan 23.

Schoolof Chemical Engineering, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea. Electronic address:

Gum karaya is a polysaccharide that has several industrial applications in the pharmaceutical, food, and environmental fields owing to its hydrophilic, anionic, and biocompatible nature. Gum karaya and its modified forms have been assessed for drug delivery, wastewater treatment, and food industry applications. This review provides a comprehensive overview of various synthetic methods of modification of gum karaya, such as grafting initiated through free radical, microwave-assisted grafting, radiation-assisted, and enzyme-assisted modification methods. In addition, the review outlines collective industrial applications of modified gum karaya in drug delivery systems, removal of heavy atoms, dyes, food, and other biological activities, and suggests possible prospects for gum karaya modification and their remarkable industrial applications.
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http://dx.doi.org/10.1016/j.carbpol.2021.117687DOI Listing
April 2021

Assessment of antiviral potencies of cannabinoids against SARS-CoV-2 using computational and in vitro approaches.

Int J Biol Macromol 2021 Jan 5;168:474-485. Epub 2020 Dec 5.

School of Chemical Engineering, Yeungnam University, Gyeongsan, Republic of Korea. Electronic address:

Effective treatment choices to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are limited because of the absence of effective target-based therapeutics. The main object of the current research was to estimate the antiviral activity of cannabinoids (CBDs) against the human coronavirus SARS-CoV-2. In the presented research work, we performed in silico and in vitro experiments to aid the sighting of lead CBDs for treating the viral infections of SARS-CoV-2. Virtual screening was carried out for interactions between 32 CBDs and the SARS-CoV-2 M enzyme. Afterward, in vitro antiviral activity was carried out of five CBDs molecules against SARS-CoV-2. Interestingly, among them, two CBDs molecules namely Δ -tetrahydrocannabinol (IC = 10.25 μM) and cannabidiol (IC = 7.91 μM) were observed to be more potent antiviral molecules against SARS-CoV-2 compared to the reference drugs lopinavir, chloroquine, and remdesivir (IC ranges of 8.16-13.15 μM). These molecules were found to have stable conformations with the active binding pocket of the SARS-CoV-2 M by molecular dynamic simulation and density functional theory. Our findings suggest cannabidiol and Δ -tetrahydrocannabinol are possible drugs against human coronavirus that might be used in combination or with other drug molecules to treat COVID-19 patients.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.12.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836687PMC
January 2021

2H/4H-Chromenes-A Versatile Biologically Attractive Scaffold.

Front Chem 2020 5;8:623. Epub 2020 Aug 5.

School of Chemical Engineering, Yeungnam University, Gyeongsan-si, South Korea.

2H/4H-chromene (2H/4H-ch) is an important class of heterocyclic compounds with versatile biological profiles, a simple structure, and mild adverse effects. Researchers discovered several routes for the synthesis of a variety of 2H/4H-ch analogs that exhibited unusual activities by multiple mechanisms. The direct assessment of activities with the parent 2H/4H-ch derivative enables an orderly analysis of the structure-activity relationship (SAR) among the series. Additionally, 2H/4H-ch have numerous exciting biological activities, such as anticancer, anticonvulsant, antimicrobial, anticholinesterase, antituberculosis, and antidiabetic activities. This review is consequently an endeavor to highlight the diverse synthetic strategies, synthetic mechanism, various biological profiles, and SARs regarding the bioactive heterocycle, 2H/4H-ch. The presented scaffold work compiled in this article will be helpful to the scientific community for designing and developing potent leads of 2H/4H-ch analogs for their promising biological activities.
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http://dx.doi.org/10.3389/fchem.2020.00623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419998PMC
August 2020

Grafting modification of okra mucilage: Recent findings, applications, and future directions.

Carbohydr Polym 2020 Oct 17;246:116653. Epub 2020 Jun 17.

School of Chemical Engineering, Yeungnam University, 280 Daehak-Ro, Gyeongsan, 38541, Republic of Korea. Electronic address:

Okra polysaccharides are biocompatible polymers with antimicrobial, anticancer, hypoglycemic, and antioxidant characteristics and hence are used in different fields such as drug delivery, food industry, and wastewater treatment. Consequently, okra-polymer modification by different methods, such as grafting, to satisfy industrial demands is attracting much scientific attention. Although a large body of literature is available on the extraction of okra polysaccharides and their applications, little is known about their grafting modification. While crosslinking and binary grafting can help in the realization of the desired properties, these methods have not been widely used on okra polysaccharides. In this review, we highlight the different methods used for the extraction of okra polysaccharides and systematically summarize major findings on their grafting modification and applications in different industries. This information will help in designing experimental protocols for the modification of okra polysaccharides to suit future needs.
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http://dx.doi.org/10.1016/j.carbpol.2020.116653DOI Listing
October 2020

Pharmacophore generation, Quantitative Structure Activity Relationship (QSAR), and Molecular Dynamic Simulation of newly substituted N-(6-Chloro-3-cyano-4-phenyl-4H-chromen-2-yl)-2-(4-chloro-phenoxy)-acetamide for anticancer activity.

Curr Comput Aided Drug Des 2020 May 25. Epub 2020 May 25.

Gyan Vihar School of Pharmacy, Suresh Gyan vihar University, Jaipur, Rajasthan. India.

Aim And Objective: The main objective of the study was to develop the Quantitative Structure Activity Relationship (QSAR) and pharmacophoric model by using data obtained from HT-29 cells study for the scientific community to develop potent lead molecule.

Materials And Methods: Common pharmacophore model, atom-based 3D-QSAR, and molecular dynamic (MD) simulation were carried out via computational techniques by using 4Hchromene derivatives.

Results: The reliable common pharmacophoric hypothesis, DHH13 was generated and 3.95 survival values were also found. Furthermore, the statistically significant of 3D-QSAR model was developed where we have found the r2=0.52 by using Partial least squares (PLS) regression method. Phase predicted activity and Log GI50 were demonstrated the mainly important atomic position in the backbone structure of ligands in order to ascertain anticolon cancer activity. In addition, MD simulation was carried out between top rank lead with IL-6 target which provided and also defined the better binding conformational and complex stability into the active pocket of target throughout the MD simulation.

Conclusion: The final outcome from this design approach shows that the pharmacophoric model and 3D-QSAR might be helpful in the medicinal chemistry field for the researcher to develop the potential anticolon cancer compounds.
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http://dx.doi.org/10.2174/1573409916666200525150410DOI Listing
May 2020

Author Correction: Novel Indole-fused benzo-oxazepines (IFBOs) inhibit invasion of hepatocellular carcinoma by targeting IL-6 mediated JAK2/STAT3 oncogenic signals.

Sci Rep 2020 Feb 6;10(1):2391. Epub 2020 Feb 6.

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raibareli Road, Lucknow, 226025, India.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-59134-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002741PMC
February 2020

Discovery of Substituted N-(6-Chloro-3-cyano-4-phenyl-4H-chromen-2-yl)- 2-(4-chloro-phenoxy)-acetamide for Biphasic Anticancer and Anticonvulsant Activities.

Med Chem 2021 ;17(3):203-215

Gyan Vihar School of Pharmacy, Suresh Gyan Vihar University, Jaipur, Rajasthan, India.

Background: Privileged 4H-chromenes possess potent anticancer and anticonvulsant activities. By the inspiring potency of 4H-chromenes and demands of the present era of scaffolds, an effective molecule was discovered for the treatment of cancer and related diseases.

Objective: This study designed and synthesized a novel series of 4H-chromene derivatives from one-port synthesis for the treatment of cancer and other such diseases.

Methods: A side amide chain was substituted in multiple steps on the amine group of chromene. Later, the anticancer activity of synthesized compounds was investigated against the human colon adenocarcinoma cell line (HT-29) using sulforhodamine B (SRB) assay. Moreover, anticonvulsant activity was also detected using maximal electroshock seizure (MES) model and subcutaneous Metrazol Seizure Threshold Test (scMET) in albino Wistar rats. Neurotoxicity was evaluated by using the rotarod test. Before the synthesis, docking studies were performed using various molecular targets. Subsequently, the computational study of the titled compounds was performed to predict the pharmacokinetic profile.

Results: Among the fifteen tested compounds, A4 and A9 were found to be active against HT-29 cells (growth inhibitory dose 50% (GI50) <11μM). Moreover, compounds A4 showed the protection at 300mg/kg in scMET (h) for albino Wistar rats and compounds A9, A11, and A15 exhibited the anticonvulsant effect at the doses 100, 300 and 300 mg/kg, respectively in MES screen (h).

Conclusion: Due to these encouraging results, we concluded that both A4 and A9 may be effective for treatement against colon cancer, while compound A9 may be used as a considerable effective molecule for the treatment of epilepsy.
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http://dx.doi.org/10.2174/1573406415666191206101617DOI Listing
January 2021

Novel binary grafted chitosan nanocarrier for sustained release of curcumin.

Int J Biol Macromol 2019 Jun 3;131:184-191. Epub 2019 Mar 3.

Department of Chemistry, Babasaheb Bhimrao Ambedkar University (A Central University), Lucknow 226025, U.P., India. Electronic address:

The study deals with the synthesis and characterization of chitosan-g-Poly (Acrylic acid-co-Acrylamide) [chit-g-Poly (AA-co-Am)] for sustained release of curcumin. The formation of chit-g-Poly (AA-co-Am) was ascertained through various spectral, thermal, microscopic methods and zeta potential. The potential of chit-g-Poly (AA-co-Am) for drug delivery applications were investigated through pH regulated kinetic models, in vitro antibacterial assay and molecular docking studies. The study reveals antibacterial activity of chit-g-Poly (AA-co-Am) against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa along with enhanced binding with bacterial receptors. In this study, nanoparticle of curcumin drug with grafted chitosan (NpCGC) was developed as effective nano therapeutic drug delivery system. Kinetic data of NpCGC reveals that the enhanced release of curcumin from NpCGC has been occurred at pH 5.4. The present study provides an economical and eco-friendly approach towards the preparation of chit-g-Poly (AA-co-Am) for sustained drug delivery applications.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.03.008DOI Listing
June 2019

Novel Indole-fused benzo-oxazepines (IFBOs) inhibit invasion of hepatocellular carcinoma by targeting IL-6 mediated JAK2/STAT3 oncogenic signals.

Sci Rep 2018 04 12;8(1):5932. Epub 2018 Apr 12.

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raibareli Road, Lucknow, 226025, India.

Inspired by the well-documented tumor protecting ability of paullones, recently, we synthesized novel paullone-like scaffolds, indole-fused benzo-oxazepines (IFBOs), and screened them against hepatocellular carcinoma (HCC) specific Hep-G2 cells. Three of the synthesized compounds significantly attenuated the progression of HCC in vitro. By computational studies, we further discovered that IFBOs exhibited a stable binding complex with the IL-6 receptor. In this context, we investigated in vivo study using the nitrosodiethyl amine (NDEA)-induced HCC model, which strengthened our previous findings by showing the blockade of the IL-6 mediated JAK2/STAT3 oncogenic signaling pathway. Treatment with IFBOs showed remarkable attenuation of cellular proliferation, as evidenced through a decrease in the number of nodules, restoration of body weight, oxidative stress parameters, liver marker enzymes and histological architecture. Interestingly, using a metabolomic approach we further discovered that IFBOs can restore the perturbed metabolic profile associated with the HCC condition to normalcy. Particularly, the efficacy of compound 6a for an anti-HCC response was significantly better than the marketed chemotherapeutic drug, 5-fluorouracil. Altogether, these remarkable findings open up possibilities of developing IFBOs as novel future candidate molecules for plausible alternatives for HCC treatment.
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http://dx.doi.org/10.1038/s41598-018-24288-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5897576PMC
April 2018

Novel 1,3,4-thiadiazoles inhibit colorectal cancer via blockade of IL-6/COX-2 mediated JAK2/STAT3 signals as evidenced through data-based mathematical modeling.

Cytokine 2019 06 23;118:144-159. Epub 2018 Mar 23.

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raibareli Road, Lucknow 226025, India. Electronic address:

We attempted a preclinical study using DMH-induced CRC rat model to evaluate the antitumor potential of our recently synthesized 1,3,4-thiadiazoles. The molecular insights were confirmed through ELISA, qRT-PCR and western blot analyses. The CRC condition was produced in response to COX-2 and IL-6 induced activation of JAK2/STAT3 which, in turn, was due to the enhanced phosphorylation of JAK2 and STAT3. The treatment with 1,3,4-thiadiazole derivatives (VR24 and VR27) caused the significant blockade of this signaling pathway. The behavior of STAT3 populations in response to IL-6 and COX-2 stimulations was further confirmed through data-based mathematical modeling using the quantitative western blot data. Finally, VR24 and VR27 restored the perturbed metabolites associated to DMH-induced CRC as evidenced through H NMR based serum metabolomics. The tumor protecting ability of VR24 and VR27 was found comparable or to some degree better than the marketed chemotherapeutics, 5-flurouracil.
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http://dx.doi.org/10.1016/j.cyto.2018.03.026DOI Listing
June 2019

Poly(lactic--glycolic acid)-loaded nanoparticles of betulinic acid for improved treatment of hepatic cancer: characterization, in vitro and in vivo evaluations.

Int J Nanomedicine 2018 16;13:975-990. Epub 2018 Feb 16.

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Lucknow, Uttar Pradesh, India.

Purpose: The application of betulinic acid (B), a potent antineoplastic agent, is limited due to poor bioavailability, short plasma half-life and inappropriate tissue distribution. Thus, we aimed to prepare novel 50:50 poly(lactic--glycolic acid) (PLGA)-loaded B nanoparticles (BNP) and to compare its anti-hepatocellular carcinoma (HCC) activity with parent B.

Methods: BNP were synthesized and characterized using different methods such as scanning electron microscopy (SEM), fourier-transform infrared (FTIR) spectrometry and particle size analyses. Particle size of BNP was optimized through the application of the stabilizer, polyvinyl alcohol (PVA). The anti-HCC response was evaluated through in vitro cell line study using Hep-G2 cells, confocal microscopy, in vivo oral pharmacokinetics and animal studies. Further, quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was conducted to observe the changes in the expression of specific genes.

Results: Particle size of BNP was optimized through the application of the stabilizer, polyvinyl alcohol. Physicochemical characterization exhibited particle size of 257.1 nm with zeta potential -0.170 mV (optimized batch B, BNP). SEM and FTIR analyses of BNP showed that cylindrical particles of B converted to spherical particles in BNP and there were no interaction between B and used polymers. The release study of optimized BNP was highest (≥80%) than any other formulation. Later, in vitro cell culture analysis using Hep-G2 cells and confocal microscopy studies revealed that BNP had the highest inhibition and penetration properties than parent B. Oral pharmacokinetics studies using albino Wistar rats at single 100 mg dose again exhibited BNP had the higher 50% of plasma concentration (t), a higher maximum plasma concentration () and took longer to reach the maximum plasma concentration (T) than parent B. Next, our in vivo study using nitrosodiethyl amine (NDEA)-induced HCC model documented BNP decreased in number of nodules, restored body weight, oxidative stress parameters, liver marker enzymes and histological architecture than parent B. Lastly, qRT-PCR studies further demonstrated that anti-HCC properties of BNP may be due to over expression of antiapoptotic caspases i.e., caspase 3 and 8.

Conclusion: The prepared BNP showed a better therapeutic response against HCC and could be attributed as future candidate molecule for HCC treatment.
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http://dx.doi.org/10.2147/IJN.S157391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818879PMC
May 2018

Novel fused oxazepino-indoles (FOIs) attenuate liver carcinogenesis via IL-6/JAK2/STAT3 signaling blockade as evidenced through data-based mathematical modeling.

Life Sci 2018 May 24;201:161-172. Epub 2018 Feb 24.

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raibareli Road, Lucknow 226025, India. Electronic address:

Aims: To potentiate the well-documented tumor protecting ability of paullones, literatures demand for rational modifications in paullone ring structure and exploration of a precise mechanism underlying their antitumor effects. Thus, recently we synthesized novel paullone-like scaffold, 5H-benzo [2, 3][1,4]oxazepino[5,6-b]indoles, where compounds 13a and 14a attenuated the growth of liver cancer specific Hep-G2 cells in vitro and formed stable binding complex with IL-6. Henceforth, we hypothesized that this action is probably due to the blockade of IL-6 mediated JAK2/STAT3 signaling cascade.

Main Methods: A preclinical study was conducted using NDEA-induced HCC rat model by oral administration of FOIs at 10 mg/kg dose for 15 days. The molecular insights were confirmed through ELISA, qRT-PCR, western blot analyses. The study was further confirmed by data-based mathematical modeling using the quantitative data obtained from western blot analysis. H NMR based metabolomics study was also performed to unveil metabolite discriminations among various studied groups.

Key Findings: We identified that the HCC condition was produced due to the IL-6 induced activation of JAK2 and STAT3 which, in turn, was due to enhanced phosphorylation of JAK2 and STAT3. The treatment with FOIs led to the significant blockade of the IL-6 mediated JAK2/STAT3 signaling pathway. Besides, FOIs showed their potential ability in restoring perturbed metabolites linked to HCC. In particular, the anticancer efficacy of compound 13a was comparable or somewhat better than marketed chemotherapeutics, 5-flurouracil.

Significance: These findings altogether opened up possibilities of developing fused oxazepino-indoles (FOIs) as new candidate molecule for plausible alternative of paullones to treat liver cancer.
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http://dx.doi.org/10.1016/j.lfs.2018.02.029DOI Listing
May 2018

6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid attenuates colon carcinogenesis via blockade of IL-6 mediated signals.

Biomed Pharmacother 2018 Apr 16;100:282-295. Epub 2018 Feb 16.

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raibareli Road, Lucknow 226025, India. Electronic address:

In this study, we investigated the in vivo antiproliferative activity of 6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid (M1) in dimethylhydrazine (DMH) induced colorectal carcinoma (CRC) using albino Wistar rats. M1 was administered to DMH induced CRC rats at 10 and 25 mg/kg doses for 15 days. Various physiological, oxidative parameters, histopathology, ELISA, gene and protein expression studies were conducted to evaluate the anti-CRC potential of M1. The histopathology and biochemical tests indicated the protective action of M1 in DMH-induced colon cancer. ELISA confirms that M1 reduced the increased concentration of IL-6 more prominently than those of IL-2 and COX-2. Gene expression analysis revealed that M1 attenuated the increased mRNA over-expression of IL-6, JAK2 and STAT3. The result obtained from quantitative western blot analysis demonstrated that the CRC condition was produced by the IL-6 induced activation/phosphorylation of JAK2 and STAT3 and further down-regulated with M1 treatment. This evidence was supported well with the application of data-based mathematical modeling. Applying the fitted model, we predicted the quantitative behavior of STAT3 populations not accessible to experimental measurement. Later, H NMR based serum metabolic profiling was carried out using rat sera to investigate the impact of M1 on CRC-induced metabolic alterations. M1 showed its ability to restore the perturbed metabolites in CRC condition. Altogether, our study provided the first time evidence that M1 exhibits anti-CRC potential through the blockade of IL-6/JAK2/STAT3 oncogenic signaling.
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http://dx.doi.org/10.1016/j.biopha.2018.02.009DOI Listing
April 2018

Molecular Docking, Pharmacophore, and 3D-QSAR Approach: Can Adenine Derivatives Exhibit Significant Inhibitor Towards Ebola Virus?

Open Med Chem J 2017 30;11:127-137. Epub 2017 Nov 30.

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, India.

Introduction: Ebola Virus Disease (EVD) is caused by Ebola virus, which is often accompanied by fatal hemorrhagic fever upon infection in humans. This virus has caused the majority of deaths in human. There are no proper vaccinations and medications available for EVD. It is pivoting the attraction of scientist to develop the potent vaccination or novel lead to inhibit Ebola virus.

Methods & Materials: In the present study, we developed 3D-QSAR and the pharmacophoric model from the previous reported potent compounds for the Ebola virus.

Results & Discussion: Results & Discussion: The pharmacophoric model AAAP.116 was generated with better survival value and selectivity. Moreover, the 3D-QSAR model also showed the best r2 value 0.99 using PLS factor. Thereby, we found the higher F value, which demonstrated the statistical significance of both the models. Furthermore, homological modeling and molecular docking study were performed to analyze the affinity of the potent lead. This showed the best binding energy and bond formation with targeted protein.

Conclusion: Finally, all the results of this study concluded that 3D-QSAR and Pharmacophore models may be helpful to search potent lead for EVD treatment in future.
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http://dx.doi.org/10.2174/1874104501711010127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748831PMC
November 2017

ω-3 Fatty Acid Synergized Novel Nanoemulsifying System for Rosuvastatin Delivery: In Vitro and In Vivo Evaluation.

AAPS PharmSciTech 2018 Apr 19;19(3):1205-1218. Epub 2017 Dec 19.

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Rae Bareli Road, Lucknow, 226025, India.

The present study was undertaken to improve rosuvastatin (RSV) bioavailability and pharmacological response through formation of SNES using Perilla frutescens oil as lipid carrier. The composition of oil was estimated by fatty acid methyl ester (FAME) analysis using gas chromatography. Solubility of RSV in Perilla frutescens oil and Cremophor EL was 25.0 ± 3.0 and 60.0 ± 5.0 mg/mL, respectively. Later, nanophasic maps and a central composite design were employed to determine the maximum nanoemulsion region and further optimize SNES in this study. Finally, the optimized formulation was evaluated in vitro and in vivo. FAME analysis revealed that PUFA content was 70.3% of total fatty acid. Optimized SNES formulation demonstrated particle size of 17.90 nm, dissolution 98.80%, cloud point 45°C, emulsification time 2 min, and viscosity 241.41 ± 5.52 cP. The hypolipidemic property of SNES was further explored using Triton X-100-induced hyperlipidemic rat model, and there were reductions of serum cholesterol, triglyceride, and LDL and VLDL levels in the SNES-treated group as compared to the toxic control. Pharmacokinetic study of SNES revealed significantly higher C (60.13 ± 25.43 ng/mL) and AUC (6195 ± 42.38 ng h/mL) vis-à-vis marketed tablet (284.80 ± 13.44 ng/mL, 3131.72 ± 51.93 ng h/mL, respectively). RSV was successfully incorporated into ω-3 fatty acid-based SNES with improved pharmacokinetic parameters (~ 2-fold improved bioavailability) and better hypolipidemic properties, owing to the synergistic effects of hepatic lipid regulation itself. The results clearly explicated that ω-3 fatty acid-based SNES effectively enhanced bioavailability and pharmacological responses of RSV, suggesting that these formulations may be useful as alternative for hyperlipidemia treatment in future drug design perspective.
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http://dx.doi.org/10.1208/s12249-017-0933-8DOI Listing
April 2018

Novel 1,4-benzothazines obliterate COX-2 mediated JAK-2/STAT-3 signals with potential regulation of oxidative and metabolic stress during colorectal cancer.

Pharmacol Res 2018 06 8;132:188-203. Epub 2017 Dec 8.

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, India. Electronic address:

1,4-benzothiazines have ameliorative effects through inhibition of COX-2 mediated STAT-3 pathways at G-protein couple receptor site. As per this scenario, we recently prepared and tested novel 1,4-benzothiazine derivatives against HT-29 human colon cancer cell line. Two compounds namely AR13 and AR15 showed higher inhibitions among all the synthesized compounds. In the present context, we conducted the in vivo antiproliferative action and identified the molecular mechanism associated to cytotoxic action of AR13 and AR15 in dimethylhydrazine (DMH) induced colorectal carcinoma (CRC) model. Various physiological, oxidative stress, histopathology, ELISA, qRT-PCR, western blot and NMR-based metabolomics were accomplished to evaluate the anticancer effect of titled compounds. Both compounds were subjected to histological and biochemical tests to observe the protective action of the compounds. ELISA showed potential role of these compounds to normalize increased levels of IL-2, IL-6 and COX-2 mediators. This action was more pronounced for COX-2 rather than IL-2 and IL-6. Gene expression analyses further revealed that both of them attenuated the over-expressed COX-2 gene. Furthermore, it was confirmed that these compounds exerted antitumor potential via preventing COX-2 induced JAK-2 and STAT-3 phosphorylation. This action was substansiated by immunohistochemistry using JAK2, p-JAK2, STAT3 and p-STAT3 targets in colon tissue. Finally, score plots of PLS-DA models exhibited significant metabolic discriminations between the treated and CRC groups, and both compounds showed ability to restore the imbalance of multiple metabolites during CRC. In conclusion, our study provided the evidence towards better antiproliferative effect of AR13 and AR15 in DMH-induced CRC through the blockade of COX-2/JAK-2/STAT-3 signal transduction pathway and could be demonstrated as useful anti-CRC candidate molecules for future anticancer therapy.
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http://dx.doi.org/10.1016/j.phrs.2017.12.010DOI Listing
June 2018

Isolated mangiferin and naringenin exert antidiabetic effect via PPAR/GLUT4 dual agonistic action with strong metabolic regulation.

Chem Biol Interact 2018 Jan 6;280:33-44. Epub 2017 Dec 6.

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, Uttar Pradesh, India. Electronic address:

In this study, we isolated two compounds from the leaves of Salacia oblonga (SA1, mangiferin and SA2, naringenin), and their structures were confirmed by infrared spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry. SA1 and SA2 were orally administered to streptozotocin-induced diabetic rats at 50 and 100 mg/kg daily for 15 days. Blood glucose level, serum lipid profile, oxidative stress parameters, histopathology, docking, molecular parameters, and NMR-based metabolic perturbation studies were performed to investigate the pharmacological activities of SA1 and SA2. Results suggested that both compounds reduced blood glucose level, restored body weight, and normalized lipid concentrations in the serum and oxidative stress biomarkers in the liver and pancreas. In addition, the docking study on several diabetes-associated targets revealed that both compounds had a strong binding affinity towards peroxisome proliferator-activated receptor gamma (PPAR) and glucose transporter type 4 (GLUT4). Further real-time reverse transcription polymerase chain reaction and western blot analyses were performed to confirm the gene and protein expression levels of PPAR and GLUT4 in the pancreatic tissues. Data obtained from the molecular studies showed that both compounds exhibited antidiabetic effects through dual activation of PPAR/GLUT4 signaling pathways. Finally, the NMR-based metabolic studies showed that both compounds normalized the diabetogenic metabolites in the serum. Altogether, we concluded that SA1 and SA2 might be potential antidiabetic lead compounds for future drug development.
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http://dx.doi.org/10.1016/j.cbi.2017.12.007DOI Listing
January 2018

A Review on the Modification of Polysaccharide Through Graft Copolymerization for Various Potential Applications.

Open Med Chem J 2017 26;11:109-126. Epub 2017 Sep 26.

Department of Applied Chemistry, MJP Rohilkhand University, Bareilly - 243006(U.P.), India.

Introduction: Graft copolymerization is one of the most promising technique uses to modify the properties of naturally available polymers with a minimum loss in their native characteristics.

Methods And Materials: Graft copolymerization is a very significant technique to add hybrid properties in backbone of polymers. The grafting generally initiated through the formation of free radical centers on the polymer backbone as well as monomer.

Results: Grafted polysaccharides have various applications in different important scientific areas such as drug delivery, pharmaceutical field, plastic industry, waste water treatment, tannery effluent treatment, textile industry, agriculture area, . all of this fascinated us to summarize the major research articles over the last two decades outlining different methods of grafting, surface modification, graft copolymerization of synthetic and natural polymers.

Conclusion: Various redox initiator systems Ceric ammonium nitrate, per sulfate, Irradiation, FAS-HO. is also explored for grafting of vinyl through conventional and non-conventional techniques.
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http://dx.doi.org/10.2174/1874104501711010109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676014PMC
September 2017

5H-benzo[h]thiazolo[2,3-b]quinazolines ameliorate NDEA-induced hepatocellular carcinogenesis in rats through IL-6 downregulation along with oxidative and metabolic stress reduction.

Drug Des Devel Ther 2017 13;11:2981-2995. Epub 2017 Oct 13.

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University.

5H-benzo[h]thiazolo[2,3-b]quinazoline scaffold is known to have an antitumor effect on certain types of malignancies; however, its effect on hepatocellular carcinoma (HCC) remains unclear. Previously, we reported -toluenesulfonic acid-promoted syntheses, molecular modeling and in vitro antitumor activity of 5H-benzo[h]thiazolo[2,3-b]quinazoline against human hepatoma (Hep-G2) cells where compounds and were found to be potent inhibitors among the series. In continuation to our previous effort to develop novel therapeutic strategies for HCC treatment, here we investigated the in vivo antitumor activity and the mechanism underlying the effects of and in N-nitrosodiethylamine (NDEA)-induced HCC using male Wistar rats. NDEA was administered weekly intraperitoneally at a dose of 100 mg/kg for 6 weeks. Various physiological and morphological changes, oxidative parameters, liver marker enzymes and cytokines were assessed to evaluate the antitumor effect of and . In addition, proton nuclear magnetic resonance-based serum metabolomics were performed to analyze the effects of and against HCC-induced metabolic alterations. Significant tumor incidences with an imbalance in carcinogen metabolizing enzymes and cellular redox status were observed in carcinogenic rats. Tumor inhibitory effects of and were noted by histopathology and biochemical profiles in NDEA-induced hepatic cancer. Compounds and had a potential role in normalizing the elevated levels of inflammatory mediators such as interleukin-1β (IL-1β), IL-2, IL-6 and IL-10. At molecular level, the real-time quantitative reverse-transcribed polymerase chain reaction analysis revealed that and attenuated the gene overexpression in hepatic cancer. Further, orthogonal partial least squares discriminant analysis scores plot demonstrated a significant separation of and -treated groups from carcinogen control group. Both the compounds have potential to restore the imbalanced metabolites due to HCC, signifying promising hepatoprotective activities. All these findings suggested that and could be potential drug candidates to treat HCC.
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http://dx.doi.org/10.2147/DDDT.S143075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648320PMC
July 2018

6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid attenuates heptatocellular carcinoma in rats with NMR-based metabolic perturbations.

Future Sci OA 2017 Aug 12;3(3):FSO202. Epub 2017 May 12.

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raibareli Road, Lucknow 226025, India.

Aim: 6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid (M1) was synthesized and evaluated for antiproliferative action in diethylnitrosamine-induced hepatocarcinogenic rats.

Materials & Methods: The antiproliferative effect of M1 was assessed by various biochemical parameters, histopathology of liver and HPLC analysis. Proton nuclear magnetic resonance-based serum metabolic study was implemented on rat sera to explore the effects of M1 on hepatocellular carcinoma-induced metabolic alterations.

Results: M1 showed protective action on liver and restored the arrangement of liver tissues in normal proportion. HPLC analysis displayed a good plasma drug concentration after its oral administration. Score plots of partial least squares discriminate analysis models exhibited that M1 therapy ameliorated hepatocellular carcinoma-induced metabolic alterations which signified its antiproliferative potential.

Conclusion: M1 manifested notable antiproliferative profile, and warrants further investigation for future anticancer therapy.
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http://dx.doi.org/10.4155/fsoa-2017-0008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583658PMC
August 2017

Indole-fused azepines and analogues as anticancer lead molecules: Privileged findings and future directions.

Eur J Med Chem 2017 Dec 4;142:244-265. Epub 2017 Aug 4.

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, India. Electronic address:

The search for new lead compounds of simple structure, displaying highest quality anti-tumor potency with new mechanisms of action and least adverse effects is the major intention of cancer drug discovery now a days. For the time being, indole-fused azepines emerged as a simple class of compounds prolifically designed with strong pharmacological significances in particular of cancer protecting ability. In the recent years from the efforts of our research group, indole-fused heteroazepines, a simple structural class achieved by fusion of indole with oxygen, sulphur and nitrogen containing heteroazepine rings, have known for its superior outcomes in cancer treatment. Surprisingly, the chemistry and biology of these unique families with an amazing role in cancer drug discovery has remained broadly unexplored. This short review is consequently an endeavor to highlight the preliminary ideas over this structural class and to draw the medical attention towards future development of indole-fused azepines and analogues for their promising function in cancer drug discovery.
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http://dx.doi.org/10.1016/j.ejmech.2017.07.042DOI Listing
December 2017

-TSA-promoted syntheses of 5H-benzo[h] thiazolo[2,3-b]quinazoline and indeno[1,2-d] thiazolo[3,2-a]pyrimidine analogs: molecular modeling and in vitro antitumor activity against hepatocellular carcinoma.

Drug Des Devel Ther 2017 29;11:1623-1642. Epub 2017 May 29.

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow, Uttar Pradesh.

In our efforts to address the rising incidence of hepatocellular carcinoma (HCC), we have made a commitment to the synthesis of novel molecules to combat Hep-G2 cells. A facile and highly efficient one-pot, multicomponent reaction has been successfully devised utilizing a -toluenesulfonic acid (-TSA)-catalyzed domino Knoevenagel/Michael/intramolecular cyclization approach for the synthesis of novel 5H-benzo[h]thiazolo[2,3-b]quinazoline and indeno[1,2-d] thiazolo[3,2-a]pyrimidine analogs bearing a bridgehead nitrogen atom. This domino protocol constructed one new ring by the concomitant formation of multiple bonds (C-C, C-N, and C=N) involving multiple steps without the use of any metal catalysts in one-pot, with all reactants effi-ciently exploited. All the newly synthesized compounds were authenticated by means of Fourier transform infrared spectroscopy, liquid chromatography-mass spectrometry, proton nuclear magnetic resonance spectroscopy, and carbon-13 nuclear magnetic resonance spectroscopy, together with elemental analysis, and their antitumor activity was evaluated in vitro on a Hep-G2 human cancer cell line by sulforhodamine B assay. Computational molecular modeling studies were carried out on cancer-related targets, including interleukin-2, interleukin-6, Caspase-3, and Caspase-8. Two compounds (4A and 6A) showed growth inhibitory activity comparable to the positive control Adriamycin, with growth inhibition of 50% <10 μg/mL. The results of the comprehensive structure-activity relationship study confirmed the assumption that two or more electronegative groups on the phenyl ring attached to the thiazolo[2,3-b]quinazoline system showed the optimum effect. The in silico simulations suggested crucial hydrogen bond and π-π stacking interactions, with a good ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile and molecular dynamics, in order to explore the molecular targets of HCC which were in complete agreement with the in vitro findings. Considering their significant anticancer activity, 4A and 6A are potential drug candidates for the management of HCC.
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http://dx.doi.org/10.2147/DDDT.S136692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459977PMC
April 2018

1,4-Benzothiazines-A Biologically Attractive Scaffold.

Mini Rev Med Chem 2018 ;18(1):42-57

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow-226025, India.

1,4-benzothiazine (1,4-B), a pharmacophore of anti-psychotic drug phenothiazines, is a vital class of heterocyclic compounds implicating versatile biological activities. The aim of this review article is to summarize various synthetic strategies, biological activities and structure activity relationship concerning the bioactive heterocycle, 1,4-B. Synthetic chemists have discovered numerous routes for the syntheses of various 1,4-B analogues that show excellent activities through multiple mechanisms. The direct comparison of activities with the parent 1,4-B derivatives enables a systematic analysis of the structure activity relationship (SAR) among the series. This review article is an effort to compile the progress in the chemistry, biological activity and SAR of 1,4-benzothiazine in a systematic way. The previously explored insights included in this article collectively suggests that 1,4-benzothiazines (1,4-Bs), besides offering several interesting biological activities, have a tremendous ability to regulate various types of cancer. The previous work on the present nucleus summarized in this article will help the researchers to design their work based on 1,4-benzothiazine ring.
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http://dx.doi.org/10.2174/1389557517666170529075556DOI Listing
January 2018

Pharmacophore, 3D-QSAR Models and Dynamic Simulation of 1,4-Benzothiazines for Colorectal Cancer Treatment.

Comb Chem High Throughput Screen 2017 ;20(8):658-674

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Rae Bareli Road, Lucknow 226025, India.

Aim And Objective: Interleukin-6 has become an attractive protein target. This is found in the progression of colon cancer. It performs various functions in the colon cancer cells such as inflammation, activates various cell types signaling and also promotes proliferation in colon cancer cells. It is a valid target to develop anticolon cancer drug. The purpose of our study is to develop the Three-dimensional Quantitative Structure-Activity Relationship (3D-QSAR) models, pharmacophore modeling and docking study as well as MD simulation to find out the novel potent inhibitors that bind with Interleukin-6 in colon cancer treatment.

Material And Methods: In this study, common pharmacophore models and atom-based 3D-QSAR studies were carried out by using 1,4-benzothiazine derivatives with their experiential GI50values towards HT-29 human colon cancer cell line.

Results: The common pharmacophore model (ADHR26) was developed and the survival score was found to be 3.828. The generated pharmacophore-based alignment was used to develop a predictive atom-based 3D-QSAR model by using Partial Least Square (PLS) method. Phase predictable activity and LogGI50 also exhibited the most significant atomic position in the backbone structure of ligands for anticolon cancer activity. Molecular dynamic and docking studies for the IL-6 target provide key framework of ligand for the anticolon cancer activity.

Conclusion: Finally, results generated from the work data, that exhibited the pharmacophore models and 3D-QSAR hypothesis might be a path of milestone in the area of medicinal chemistry to researchers for further design of new and potent IL-6 inhibitors.
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http://dx.doi.org/10.2174/1386207320666170509153137DOI Listing
December 2018

Discovery of Novel 2-Amino-5-(Substituted)-1,3,4-Thiadiazole Derivatives: New Utilities for Colon Cancer Treatment.

Anticancer Agents Med Chem 2018 ;18(5):719-738

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, India.

Background: Colon cancer is one of the most widespread disease, the mortality rate is high due to cancer metastasis and the development of drug resistance. In this regards, new chemotherapeutic agents with specific mechanisms of action and significant effect on patient's survival are the new era for the colon cancer drug development.

Objective: The main objective of present study was to design, synthesize of a novel series of 1,3,4-thiadiazole derivatives (VR1 to VR35) and screen them against HT-29 human colon cancer cell line.

Method: Newly 1,3,4-thiadiazole scaffold were designed, synthesized and further, characterized by FTIR, NMR (1H and 13C), MS and elemental analyses. Before the synthesis, molecular dynamic simulation and ADME studies were performed to find out the most potent lead compounds. Later, SRB assay using HT-29 cells and ELISA assays were performed to explore activity and molecular targets of VR24 and VR27 and find out whether in silico data had a similar pattern in the molecular level.

Results: The results of docking study revealed that both VR24 and VR27 had interaction energy >-5 kcal/mol with various assigned molecular targets and the ligand-protein complexes were found to be stable with IL-6. The computational analysis of molecules showed good ADMET profiling. Later, the in vitro anticancer study was conducted where VR24 and VR27 were found to be active against HT-29 cells (GI50<10 µM). Finally, ELISA assays revealed that both the compounds had higher inhibition properties to various biomarker of colon cancer like IL-6 and COX-2.

Conclusion: Collectively, these result suggested that VR24 and VR27 inhibited the assigned molecular targets, imparting their ameliorative effects against colon cancer. Due to these encouraging results, we concluded that both VR24 and VR27 may be effective against colon cancer therapy in future.
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http://dx.doi.org/10.2174/1871520617666170419122916DOI Listing
June 2019

Ameliorative effects of pyrazinoic acid against oxidative and metabolic stress manifested in rats with dimethylhydrazine induced colonic carcinoma.

Cancer Biol Ther 2017 05 30;18(5):304-313. Epub 2017 Mar 30.

a Department of Pharmaceutical Sciences , Babasaheb Bhimrao Ambedkar University , Vidya Vihar, Lucknow , India.

Pyrazinoic acid (PA) is structurally similar to nicotinic acid which acts on G-protein-coupled receptor (GPR109A). GPR109A expresses in colonic and intestinal epithelial sites, and involves in DNA methylation and cellular apoptosis. Therefore, it may be assumed that PA has similar action like nicotinic acid and may be effective against colorectal carcinoma (CRC). CRC was produced via subcutaneous injection of dimethylhydrazine (DMH) at 40 mg/kg body weight once in a week for 4 weeks. After that, PA was administered orally at 2 doses of 10 and 25 mg/kg daily for 15 d to observe the antiproliferative effect. Various physiologic, oxidative stress, molecular parameters, histopathology, RT-PCR and NMR based metabolomics were performed to evaluate the antiproliferative potential of PA. Our results collectively suggested that PA reduced body weight, tumor volume and incidence no. to normal. It restored various oxidative stress parameters and normalized IL-2, IL-6, and COX-2 as compared with carcinogen control. In molecular level, overexpressed IL-6 and COX-2 genes became normal after PA administration. Again, normal tissue architecture was prominent after PA administration. Score plots of PLS-DA models exhibited that PA treated groups were significantly different from CRC group. We found that CRC rat sera have increased levels of acetate, glutamine, o-acetyl-glycoprotein, succinate, citrulline, choline, o-acetyl choline, tryptophan, glycerol, creatinine, lactate, citrate and decreased levels of 3-hydroxy butyrate, dimethyl amine, glucose, maltose, myoinositol. Further the PA therapy has ameliorated the CRC-induced metabolic alterations, signifying its antiproliferative properties. In conclusion, our study provided the evidence that PA demonstrated good antiproliferative effect on DMH induced CRC and thus demonstrated the potential of PA as a useful drug for future anticancer therapy.
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http://dx.doi.org/10.1080/15384047.2017.1310341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499763PMC
May 2017

Indole-fused benzooxazepines: a new structural class of anticancer agents.

Future Sci OA 2017 Mar 4;3(1):FSO168. Epub 2017 Jan 4.

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Rae Bareli Road, Lucknow 226025, India.

Aim: A new series of compounds () bearing indole-fused benzooxazepine was synthesized, characterized and evaluated for anticancer activity.

Materials & Methods: In this study, all the synthesized compounds were screened via anticancer testing on Hep-G2 cancer cell line. A computational study was carried out on cancer-related targets including IL-2, IL-6, COX-2 Caspase-3 and Caspase-8.

Results: Some of the synthesized compounds effectively controlled the growth of cancerous cells.

Conclusion: The most active compounds - , , , and - exemplify notable anticancer profile with GI <10 μg/ml. Preliminary structure-activity relationship among the tested compounds can produce an assumption that the electronegative groups at phenyl ring attached with indole-fused benzooxazepine are instrumental for the activity. Molecular docking study showed crucial hydrogen bond and π-π stacking interactions, with good ADMET profiling and molecular dynamic simulation.
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http://dx.doi.org/10.4155/fsoa-2016-0079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351710PMC
March 2017

Human Cancer Cell Line Based Approach of 1,3,4-thiadiazole and its Fused Ring: A Comprehensive Review.

Anticancer Agents Med Chem 2017 ;17(4):500-523

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, VidyaVihar, Rai Bareli Road, Lucknow-226025, India.

The chemistry of heterocyclic containing, 1,3,4-thiadiazole has been an interesting field of study from ancient years. Subsequently, 1,3,4-thiadiazole nucleus constitutes a significant class of compounds for new drug development. Recently, various 1,3,4-thiadiazole derivatives synthesized and evaluated their biological activities including antimicrobial, antituberculosis, antioxidant, anti-inflammatory, anticonvulsants, antidepressant and anxiolytic, antihypertensive, anticancer and antifungal activity. The search for anticancer compounds with more selective activities and lower side effect continues to be an active area of argument examination in medicinal chemistry. This review elaborately described the medicinal chemistry, their structural activity relationship, and anticancer properties with respect to human cell line based approach related to synthesized 1,3,4-thiadiazole derivatives.
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http://dx.doi.org/10.2174/1871520616666161013150151DOI Listing
August 2017