Publications by authors named "Rajeev K Singla"

41 Publications

The Combination of Tradition and Future: Data-Driven Natural-Product-Based Treatments for Parkinson's Disease.

Evid Based Complement Alternat Med 2021 14;2021:9990020. Epub 2021 Jul 14.

Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.

Parkinson's disease (PD) is a neurodegenerative disorder in elderly people. The personalized diagnosis and treatment remain challenges all over the world. In recent years, natural products are becoming potential therapies for many complex diseases due to their stability and low drug resistance. With the development of informatics technologies, data-driven natural product discovery and healthcare is becoming reality. For PD, however, the relevant research and tools for natural products are quite limited. Here in this review, we summarize current available databases, tools, and models for general natural product discovery and synthesis. These useful resources could be used and integrated for future PD-specific natural product investigations. At the same time, the challenges and opportunities for future natural-product-based PD care will also be discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/9990020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294954PMC
July 2021

QSCR Analysis of Cytotoxicity of 6-Fluoro-3-(4H-1,2,4-triazol-3-yl)quinolin-4(1H)-ones on Chinese Hamster Ovary Cell Line: Design of REPUBLIC1986.

Curr Med Chem 2021 Jun 23. Epub 2021 Jun 23.

West China School of Nursing / Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.

Background: 6-Fluoro-3-(4H-1,2,4-triazol-3-yl)quinolin-4(1H)-ones are promising antitumor agents with enormous data on their profound cytotoxic effects on the human cancer cell lines.

Objectives: We sought to perform a Quantitative structure cytotoxicity relationship (QSCR) analysis of a series of previously reported fluoroquinolone analogues using computer-assisted multiple regression analysis and investigate the cytotoxicity-inducing structural parameters among these congeners.

Methods: The dataset was segregated into training and test sets of 6-Fluoro-3-(4H-1,2,4-triazol-3-yl)quinolin-4(1H)-ones by using a random selection method embedded in Vlife MDS 4.6 software and subjected to QSCR analysis. Next, cross-validation of the generated QSCR models was performed along with the external test set prediction. Finally, the data was analyzed, and contour plots were developed to deduce the cytotoxicity-inducing structural parameters among these congeners using Minitab® software.

Results: The validated QSCR model exhibited a statistically significant predictive value of 92.27 percent. Our QSCR model revealed a direct proportionality between hydrogen counts and cytotoxicity and exclusion of sulphur and nitrogen with lesser crowding of cyclopropyl rings in future potential 6-Fluoro-3-(4H-1,2,4-triazol-3-yl)quinolin-4(1H)-one analogues. Based on the QSCR model predictions and contour plot analysis, the de novo REPUBLIC1986 molecule provided the best hit with predicted IC50 (µM) of 0.45 against CHO cell line and is amenable to salt formation crucial for anti-ovarian cancer activity.

Conclusion: These findings suggest the relevancy of the developed QSCR model in designing novel, potent, and safer anti-cancer drugs with 6-Fluoro-3-(4H-1,2,4-triazol-3-yl)quinolin-4(1H)-ones as seed compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/0929867328666210623150552DOI Listing
June 2021

Editorial: Application of Plant Secondary Metabolites to Pain Neuromodulation.

Front Pharmacol 2020 14;11:623399. Epub 2021 Jan 14.

Department of Biology, Faculty of Science, Selcuk University Campus, Konya, Turkey.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.623399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841409PMC
January 2021

Secondary Metabolites as Treatment of Choice for Metabolic Disorders and Infectious Diseases & their Metabolic Profiling-Part 2.

Curr Drug Metab 2020;21(14):1070-1071

Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/138920022114201230142204DOI Listing
January 2020

Topical Capsaicin for the Treatment of Neuropathic Pain.

Curr Drug Metab 2021 ;22(3):198-207

Center for Systems Biology, Soochow University, Suzhou, 215006, China.

Background: Neuropathic pain (NP) is an egregious problem worldwide. Due to the side-effects of oral drugs, drugs delivered directly to the affected area of pain are preferred.

Objective: Capsaicin, a chemical compound isolated from chili peppers, is used as an analgesic in topical ointments and dermal patches to alleviate pain. Objective of the study is to review the application and functionality of topical capsaicin in treatment of neuropathic pain.

Data Sources: To systematically review capsaicin's functions on NP, we retrieved articles from the PubMed database published in the last ten years.

Study Eligibility Criteria: The inclusion criteria were capsaicin and the use of capsaicin for the treatment of NP; on the other hand, articles were excluded according to the mentioned criteria such as abstracts, articles written in any language other than English, incomplete articles, and conference papers.

Participants And Interventions: Out of 265 articles, 108 articles were selected after filtering through the inclusion and exclusion criteria. The data and knowledge currently existing for capsaicin treatment in NP are summarized.

Results: This review indicates that capsaicin effectively improves NP treatment without affecting the motor and large nerve fibres involved in sensory function. Transient receptor potential channel vanilloid type 1 (TRPV1) is the capsaicin receptor expressed in central and peripheral terminals of a sensitive primary nerve cell. Conclusions and implications of key findings: Topical capsaicin has a sensible safety profile and is effective in reducing NP. Therefore, studies over the last decade suggest that capsaicin might be a potential drug for NP treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1389200221999201116143701DOI Listing
January 2021

Regulation of Pain Genes-Capsaicin vs Resiniferatoxin: Reassessment of Transcriptomic Data.

Front Pharmacol 2020 29;11:551786. Epub 2020 Oct 29.

Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.

Emerging evidence has shown a strong association between neuropathic pain and chronic diseases. In recent years, the treatment of neuropathic pain has attracted more attention. Natural products, such as capsaicin and resiniferatoxin, have been well utilized to treat this disease. In this study, we aim to compare the regulatory effects of capsaicin and resiniferatoxin on pain-related genes as well as on genes with no direct association with pain. Public transcriptomic and microarray data on gene expression in the dorsal root ganglia and genes associated with TRPV1 (+) neurons were obtained from the GEO database and then analyzed. Differentially expressed genes were selected for further functional analysis, including pathway enrichment, protein-protein interaction, and regulatory network analysis. Pain-associated genes were extracted with the reference of two pain gene databases and the effects of these two natural drugs on the pain-associated genes were measured. The results of our research indicate that as compared to capsaicin, resiniferatoxin (RTX) regulates more non pain-associated genes and has a negative impact on beneficial genes (off-targets) which are supposed to alleviate nociception and hypersensitivity by themselves. So, based on this study, we may conclude that capsaicin may be less potent when compared to RTX, but it will elicit considerably less adverse effects too. Thereby confirming that capsaicin could be used for the efficient alleviation of neuropathic pain with possibly fewer side effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.551786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658921PMC
October 2020

Secondary Metabolites as Treatment of Choice for Metabolic Disorders and Infectious Diseases and their Metabolic Profiling: Part 1.

Authors:
Rajeev K Singla

Curr Drug Metab 2020;21(7):480-481

Institutes for Systems Genetics Frontiers Science Center for Disease-related Molecular Network West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/138920022107200925101631DOI Listing
January 2020

Herbal Resources to Combat a Progressive & Degenerative Nervous System Disorder- Parkinson's Disease.

Curr Drug Targets 2021 ;22(6):609-630

Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Xinchuan Road 2222, Chengdu, Sichuan, China.

Parkinson's disease is one of the most common adult-onset, a chronic disorder involving neurodegeneration, which progressively leads to deprivation of dopaminergic neurons in substantia nigra, causing a subsequent reduction of dopamine levels in the striatum resulting in tremor, myotonia, and dyskinesia. Genetics and environmental factors are believed to be responsible for the onset of Parkinson's disease. The exact pathogenesis of Parkinson's disease is quite complicated and the present anti-Parkinson's disease treatments appear to be clinically insufficient. Comprehensive researches have demonstrated the use of natural products such as ginseng, curcumin, ashwagandha, baicalein, etc. for the symptomatic treatment of this disease. The neuroprotective effects exhibited by these natural products are mainly due to their ability to increase dopamine levels in the striatum, manage oxidative stress, mitochondrial dysfunction, glutathione levels, clear the aggregation of α- synuclein, induce autophagy and decrease the pro-inflammatory cytokines and lipid peroxidation. This paper reviews various natural product studies conducted by scientists to establish the role of natural products (both metabolite extracts as well as pure metabolites) as adjunctive neuroprotective agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1389450121999201013155202DOI Listing
January 2021

Data-driven microbiota biomarker discovery for personalized drug therapy of cardiovascular disease.

Pharmacol Res 2020 11 29;161:105225. Epub 2020 Sep 29.

Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address:

Cardiovascular disease (CVD) is the most wide-spread disorder all over the world. The personalized and precision diagnosis, treatment and prevention of CVD is still a challenge. With the developing of metagenome sequencing technologies and the paradigm shifting to data-driven discovery in life science, the computer aided microbiota biomarker discovery for CVD is becoming reality. We here summarize the data resources, knowledgebases and computational models available for CVD microbiota biomarker discovery, and review the present status of the findings about the microbiota patterns associated with the therapeutic effects on CVD. The future challenges and opportunities of the translational informatics on the personalized drug usages in CVD diagnosis, prognosis and treatment are also discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2020.105225DOI Listing
November 2020

ADMET Evaluation of Natural DPP-IV Inhibitors for Rational Drug Design against Diabetes.

Curr Drug Metab 2020 ;21(10):768-777

Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Xinchuan Road 2222, Chengdu, Sichuan, China.

Background: As a metabolic and lifestyle disorder, diabetes mellitus poses a prodigious health risk. Out of the many key targets, DPP-IV is one of the very imperative therapeutic targets for the treatment of diabetic patients.

Methods: In our current study, we have done the in silico simulations of ADME-T properties for naturally originated potent DPP-IV inhibitors like quinovic acid, stigmasterol, quinovic acid-3-beta-D-glycopyranoside, zygophyloside E, and lupeol. Structural topographies associated with different pharmacokinetic properties have been systematically assessed.

Results: Glycosylation on quinovic acid is found to be noteworthy for the improvement of pharmacokinetic and toxicological properties, which leads to the prediction that zygophyloside E can be further tailored down to get the lead DPP-IV inhibitor.

Conclusion: This assessment provides useful insight into the future development of novel drugs for the treatment of diabetes mellitus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1389200221999200901202945DOI Listing
January 2020

Current Trends in Anti-Candida Drug Development.

Curr Top Med Chem 2019;19(28):2525-2526

School of Medical & Allied Sciences KR Mangalam University Gurugram, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/156802661928191206162925DOI Listing
February 2020

Perspectives on Anti-Candida Drug Development.

Curr Top Med Chem 2019;19(26):2375-2376

School of Medical & Allied Sciences, KR Mangalam University, Gurugram, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/156802661926191114102349DOI Listing
December 2019

Molecules and Metabolites from Natural Products as Inhibitors of Biofilm in Candida spp. pathogens.

Curr Top Med Chem 2019 ;19(28):2567-2578

Drug Discovery Laboratory, Department of Biological Sciences and Engineering, Netaji Subhas University of Technology, New Delhi-110078, India.

Background: Biofilm is a critical virulence factor associated with the strains of Candida spp. pathogens as it confers significant resistance to the pathogen against antifungal drugs.

Methods: A systematic review of the literature was undertaken by focusing on natural products, which have been reported to inhibit biofilms produced by Candida spp. The databases explored were from PubMed and Google Scholar. The abstracts and full text of the manuscripts from the literature were analyzed and included if found significant.

Results: Medicinal plants from the order Lamiales, Apiales, Asterales, Myrtales, Sapindales, Acorales, Poales and Laurales were reported to inhibit the biofilms formed by Candida spp. From the microbiological sources, lactobacilli, Streptomyces chrestomyceticus and Streptococcus thermophilus B had shown the strong biofilm inhibition potential. Further, the diverse nature of the compounds from classes like terpenoids, phenylpropanoid, alkaloids, flavonoids, polyphenol, naphthoquinone and saponin was found to be significant in inhibiting the biofilm of Candida spp.

Conclusion: Natural products from both plant and microbial origins have proven themselves as a goldmine for isolating the potential biofilm inhibitors with a specific or multi-locus mechanism of action. Structural and functional characterization of the bioactive molecules from active extracts should be the next line of approach along with the thorough exploration of the mechanism of action for the already identified bioactive molecules.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1568026619666191025154834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403689PMC
February 2020

Phenolic Substances in Foods: Health Effects as Anti-Inflammatory and Antimicrobial Agents.

J AOAC Int 2019 Sep 14;102(5):1378-1387. Epub 2019 Jun 14.

Institute for Biological Resources and Marine Biotechnologies, Messina 98123, Italy.

The interest in phenolic compounds present in foods of vegetable origin has shown a notable increase in recent decades. This interest is due to the growing number of scientific studies concerning their beneficial role in human health. The interest in polyphenols has been supported by the current and growing awareness, and attention of consumers to food from a food safety viewpoint and also because of the beneficial effects ascribed to polyphenols. The aim of this article is to highlight antibacterial, antifungal, and anti-inflammatory activities of various phenolic compounds normally found in certain foods. Phenolic compounds exert different biological functions, such as antioxidant activity, modulation of detoxifying enzymes, stimulation of the immune system, reduction of platelet aggregation, modulation of hormonal metabolism, reduction of blood pressure, and anti-inflammatory, antibacterial, antiviral, and antifungal activities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5740/jaoacint.19-0131DOI Listing
September 2019

Natural Polyphenols: Chemical Classification, Definition of Classes, Subcategories, and Structures.

J AOAC Int 2019 Sep 14;102(5):1397-1400. Epub 2019 Jun 14.

National Agricultural Research Center, Al-Baqah 19110, Jordan.

Polyphenols are natural compounds synthesized exclusively by plants with chemical features related to phenolic substances and eliciting strong antioxidants properties. The aim of this paper is to give a reliable overview of the chemical classification of natural polyphenols. Literature survey was done through google scholar, pubmed and scopus search engine. These molecules or classes of natural substances are characterized by two phenyl rings at least and one or more hydroxyl substituents. This description comprehends a large number of heterogeneous compounds with reference to their complexity. Therefore, polyphenols can be simply classified into flavonoids and non-flavonoids, or be subdivided in many sub-classes depending on the number of phenol units within their molecular structure, substituent groups, and/or the linkage type between phenol units. Polyphenols are widely distributed in plant tissues where they mainly exist in form of glycosides or aglycones. The structural diversity of flavonoid molecules arises from variations in hydroxylation pattern and oxidation state resulting in a wide range of compounds: flavanols, anthocyanidins, anthocyanins, isoflavones, flavones, flavonols, flavanones, and flavanonols.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5740/jaoacint.19-0133DOI Listing
September 2019

Studies on the Determination of Antioxidant Activity and Phenolic Content of Plant Products in India (2000-2017).

J AOAC Int 2019 Sep 14;102(5):1407-1413. Epub 2019 Jun 14.

K.R. Mangalam University, School of Medical and Allied Sciences, Drug Design and Discovery Laboratory, Gurugram 122103, India.

Ayurveda, the traditional Indian therapeutic system, involves herbs and spices as drug ingredients and a kind of food intake regulation. The health and curative aspects of plant products are often ascribed to their antimicrobial and antioxidant activities (AA). However, it seems somewhat possible to correlate the AA of herbal extracts or plant isolates with their phenolic contents (PC). Indian researchers have carried out some tests for the determination of AA and PC of plant products that are worth mentioning. Among the herbal analysis techniques, the important contributions of Indians and people of Indian origin in this field include the remarkable separation of phenolic compounds, including the use of reversed-phase columns, on-line HPLC, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay to effectively screen and identify antioxidant compounds from herbal extracts, and other chromatographic, spectrographic, and spectroscopic techniques, in the analysis of complex biological matrices. The aim of this paper is to present an overview of such arguments with reference to herbal drugs and food intake regulation for specific ailments. The lack of uniformity in the use of test protocols for antioxidant assays (particularly using the DPPH free radical) and differences in in vitro mechanisms of antiradical activity and in vivo metabolism of polyphenols have been the issues associated with these experiments that have been raised by researchers in the period from 2000 onward.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5740/jaoacint.19-0136DOI Listing
September 2019

Natural Products: Potential Source of DPP-IV Inhibitors.

Curr Protein Pept Sci 2019 ;20(12):1218-1225

Drug Design & Discovery Laboratory, School of Medical and Allied Sciences, K.R. Mangalam University, Sohna Road, Gurugram, India.

Out of multiple therapeutic targets, DPP-IV is the lead target for the treatment of type 2 diabetes. Natural products have always been available for the possible lead generation against various diseases and disorders. In the present review, we have covered various natural sources which have experimentally validated anti-diabetic activity for type 2 diabetic patients with specific focus on the DPP-IV inhibition. Out of all, the most potent DPP-IV inhibitors were found to be resveratrol, luteolin, apigenin and flavone having activity in nanomolar range. Standard drugs like sitagliptin, saxagliptin, and diprotin A have complex structures as compared to these phenolic compounds. Flavonoids and phenolic compounds have their added advantages in being present in a number of functional foods and carry antioxidant properties as well. So, the scientists working on the new chemical entity hunting for the type 2 diabetes treatment can also explore these natural sources for lead generation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1389203720666190502154129DOI Listing
February 2020

Isolation and Characterization of Nuciferoic Acid, a Novel Keto Fatty Acid with Hyaluronidase Inhibitory Activity from Cocos nucifera Linn. Endocarp.

Curr Top Med Chem 2018 ;18(27):2367-2378

Division of Biological Sciences and Engineering, Netaji Subhas University of Technology, Sector - 3, Dwarka, New Delhi-110078, India.

Background: Inflammation and oxidative stress are very closely related to pathophysiological processes and linked to multiple chronic diseases. Traditionally, the coconut fruits were used in Guatemala for treatment of dermatitis and inflammation. Isolation of the anti-inflammatory agent from the hard shell of the coconut fruit was targeted in the current study.

Methods: Fractionation of ethanolic extract of the coconut hard shell was done by using column chromatography, solvent treatments and TLC that led to the isolation of a molecule.

Results And Discussion: Spectral characterization of the molecule by LC-MS/MS QTOF, FTIR, 1HNMR, 13C-NMR, HMQC and HMBC indicated that it is a novel keto fatty acid, which is named as nuciferoic acid. Hyaluronidase inhibitory potential of the nuciferoic acid was found to be moderate. It was further docked in all the ten cavities of hyaluronidase and was compared with the substrate hyaluronic acid. Cavity 1 and cavity 4 could be the probable sites of action on hyaluronidase for nuciferoic acid. ADME and toxicological characterization suggested that the key sites of metabolism on nuciferoic acid are C1, C2, C14 and C17. Toxicity prediction against 55 toxicological endpoints revealed that nuciferoic acid does not have any indication of existing toxicological features.

Conclusion: A novel keto fatty acid, nuciferoic acid, from C. nucifera hard shell has been isolated and characterized. It was found to inhibit hyaluronidase activity, which indicated its potential application as an anti-inflammatory drug or as an adjuvant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1568026619666181224111319DOI Listing
April 2019

Inhibition of Biofilm and Virulence Factors of Candida albicans by Partially Purified Secondary Metabolites of Streptomyces chrestomyceticus Strain ADP4.

Curr Top Med Chem 2018 ;18(11):925-945

Division of Biological Sciences and Engineering, Netaji Subhas Institute of Technology, Dwarka, New Delhi 110078, India.

Background: Despite several advancements in antifungal drug discovery, fungal diseases like Invasive Candidiasis (IC) still remain associated with high rates of morbidity and mortality worldwide. Thus there is an enormous need for anti-Candida drugs.

Objective: The main objectives of the work included: 1. To investigate therapeutically significant classes of secondary metabolites produced by S. chrestomyceticus strain ADP4. 2. To investigate and analyze inhibition of significant virulence attributes of C. albicans, such as, biofilm and secretory hydrolytic enzymes by ADP4 secondary metabolites. 3. Mechanistic analysis of probable compounds for their site of action on Secretary Aspartyl Proteinase 3 (Sap3).

Methods: Metabolite extract-SDB (MESDB) of S. chrestomyceticus strain ADP4 was fractionated on silica gel column chromatography. Fractions were analyzed for anti-Candida activity by disc diffusion assay. Active fractions were further purified by differential solvent treatment. MIC90 values were determined by broth dilution method. MFC was based on counting viable cells. Inhibition of yeast to hyphae transition and that of production of hydrolytic enzymes were estimated by plate assays. GC-MS of MESDB and Partially Purified Metabolite preparations (PPMs) was done. GRIP docking studies with Sap 3 of C. albicans was done using VLife MDS 4.6 software.

Results: Chemical profiling showed that ADP4 secondary metabolites contained alkaloids, flavonoids, polyphenols, terpenoids and triterpenes. The MESDB and the PPMs showed low or no cytotoxicity but were able to effectively contain virulence attributes of Candida pathogen. Docking studies revealed that some of the probable compounds have affinity for aspartic acid residue in Sap3 enzyme of C. albicans.

Conclusion: Secondary metabolite of strain ADP4 included important classes of therapeutically important compounds. Their anti-Candida activity was mediated by inhibition of critical virulence factors of the pathogen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1568026618666180711154110DOI Listing
September 2018

Diabetes Mellitus and Male Aging: Pharmacotherapeutics and Clinical Implications.

Curr Pharm Des 2017 ;23(30):4475-4483

King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah 21589, Saudi Arabia.

Andropause or male menopause is defined as androgen decline and onset of hypogonadism in the aging male. Testosterone deficiency in adult male is associated with diabetes mellitus, coronary artery disease, and heart failure. Type 2 diabetic male patients aged above 30 years showed low testosterone levels which is common in diabetic men and had symptoms of hypogonadism. Male sexual dysfunction among diabetic patients can include disorders of libido, ejaculatory problems, and erectile dysfunctions are common among people with diabetes, particularly in older men who had diabetes for years. Older diabetics tend to have both impaired insulin release as well as insulin resistance. There is growing evidence indicating the pathophysiological connections among the mechanisms of oxidative damage by disruption of the oxidative balance, increased levels of enzymatic glycation products in testicular region and glucose transporters, obesity and proinflammatory cytokines in male infertile patients with diabetes. Epidemiological studies suggest that many clinical findings in diabetics are linked to low testosterone levels. This article reviews pathophysiological mechanisms, observational studies, and clinical implications of testosterone therapy in type 2 diabetes mellitus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1381612823666170823103830DOI Listing
January 2017

Antioxidant activity and protective effect of suramin against oxidative stress in collagen induced arthritis.

Eur J Pharm Sci 2017 Apr 9;101:125-139. Epub 2017 Feb 9.

Product Development Cell, National Institute of Immunology, New Delhi 110067, India. Electronic address:

It is imperative to interrupt the link between arthritis and regulation of oxidative stress with the administration of antioxidants. Suramin is known for its anti-inflammatory, antineoplastic and antiangiogenic activities implying its possible antioxidant property. In this study, the antioxidant activity of suramin in cell free system was found to be higher than l-ascorbic acid (l-AA) with respect to its scavenging effect on nitric oxide (NO), hypochlorous acid and hydrogen peroxide radicals. Besides, suramin was found to be nontoxic to cultured RAW cells even at high concentrations along with marked inhibition of NO production. Suramin was found to curb the inflammation associated with the collagen induced arthritis (CIA) model. Administration of suramin significantly reduced the malondialdehyde and protein carbonyl content in joints, liver, kidney and spleen of rats as studied ex vivo. Furthermore, the increased antioxidant enzymes such as SOD, catalase, GST, GPx and GR activities in the tissues were restored significantly after suramin treatment. In silico experiments using Vlife MDS4.4-GRIP docking method showed strong affinity of suramin towards erythrocyte catalase followed by glutathione peroxidase thus corroborating with the findings of antioxidant enzyme assays. Our studies clearly indicate that suramin has remarkable antioxidant potential and can ameliorate arthritis via modulation of oxidative stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejps.2017.02.013DOI Listing
April 2017

In Silico Studies Revealed Multiple Neurological Targets for the Antidepressant Molecule Ursolic Acid.

Curr Neuropharmacol 2017 Nov;15(8):1100-1106

Division of Biological Sciences and Engineering, Netaji Subhas Institute of Technology, Sector-3, Dwarka, New Delhi, 110078, India.

Background: Ursolic acid, a bioactive pentacyclic triterpenoid had been evaluated for its interaction with the neurological targets associated with antidepressant drugs. Current study was to mechanistically analyze the probable site of action for ursolic acid on the target proteins.

Methods: Ursolic acid has been docked with monoamine oxidase isoforms: MAO-A and MAO-B, LeuT (homologue of SERT, NET, DAT) and Human C-terminal CAP1 using GRIP docking methodology.

Results: Results revealed its non-selective antidepressant action with strong binding affinity towards LeuT and MAO-A proteins, which was found to be comparable with the reference ligands like chlorgyline, clomipramine, sertraline and deprenyl/selegiline.

Conclusion: Significant binding affinity of ursolic acid was seen with MAO-A, which indicated its potential role in other neurological disorders, for example, Alzheimer's disease and Parkinson disease besides depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1570159X14666161229115508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725542PMC
November 2017

Perspectives in Medicinal Chemistry.

Curr Top Med Chem 2016 ;16(25):2725-6

Federal University of Paraíba, Health Center, 50670-910, João Pessoa, PB, Brazil.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/156802661625160816180839DOI Listing
February 2017

Editorial (Thematic Issue: Natural Leads in Drug Discovery against Metabolic Disorders and their Related Infectious Diseases).

Curr Top Med Chem 2016 ;16(23):2523-4

Federal University of Paraíba Department of Engineering and the Environment Campus IV; 58297-000, Rio Tinto PB, Brazil.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1568026616999160510121418DOI Listing
February 2017

Editorial: Natural Leads in Drug Discovery against Metabolic Disorders and their Related Infectious Diseases.

Curr Top Med Chem 2016 May 23. Epub 2016 May 23.

Federal University of Paraíba Department of Engineering and the Environment Campus IV; 58297-000, Rio Tinto PB, Brazil.

View Article and Find Full Text PDF

Download full-text PDF

Source
May 2016

Perspectives in Medicinal Chemistry.

Curr Top Med Chem 2016 May 10. Epub 2016 May 10.

Federal University of Paraíba, Department of Engineering and the Environment, Campus IV; 58297-000, Rio Tinto, PB, Brazil.

View Article and Find Full Text PDF

Download full-text PDF

Source
May 2016

Chemometrics Optimized Extraction Procedures, Phytosynergistic Blending and in vitro Screening of Natural Enzyme Inhibitors Amongst Leaves of Tulsi, Banyan and Jamun.

Pharmacogn Mag 2015 Oct;11(Suppl 4):S522-32

School of Medical Science and Technology, IIT Kharagpur, India.

Background: Tulsi, Banyan, and Jamun are popular Indian medicinal plants with notable hypoglycemic potentials. Now the work reports chemo-profiling of the three species with in-vitro screening approach for natural enzyme inhibitors (NEIs) against enzymes pathogenic for type 2 diabetes. Further along with the chemometrics optimized extraction process technology, phyto-synergistic studies of the composite polyherbal blends have also been reported.

Objective: Chemometrically optimized extraction procedures, ratios of polyherbal composites to achieve phyto-synergistic actions, and in-vitro screening of NEIs amongst leaves of Tulsi, Banyan, and Jamun.

Materials And Methods: The extraction process parameters of the leaves of three plant species (Ficus benghalensis, Syzigium cumini and Ocimum sanctum) were optimized by rotatable central composite design of chemometrics so as to get maximal yield of bio-actives. Phyto-blends of three species were prepared so as to achieve synergistic antidiabetic and antioxidant potentials and the ratios were optimized by chemometrics. Next, for in vitro screening of natural enzyme inhibitors the individual leaf extracts as well as composite blends were subjected to assay procedures to see their inhibitory potentials against the enzymes pathogenic in type 2 diabetes. The antioxidant potentials were also estimated by DPPH radical scavenging, ABTS, FRAP and Dot Blot assay.

Results: Considering response surface methodology studies and from the solutions obtained using desirability function, it was found that hydro-ethanolic or methanolic solvent ratio of 52.46 ± 1.6 and at a temperature of 20.17 ± 0.6 gave an optimum yield of polyphenols with minimal chlorophyll leaching. The species also showed the presence of glycosides, alkaloids, and saponins. Composites in the ratios of 1:1:1 and 1:1:2 gave synergistic effects in terms of polyphenol yield and anti-oxidant potentials. All composites (1:1:1, 1:2:1, 2:1:1, 1:1:2) showed synergistic anti-oxidant actions. Inhibitory activities against the targeted enzymes expressed in terms of IC50 values have shown that hydro-ethanolic extracts in all cases whether individual species or composites in varying ratios gave higher IC50 values thus showing greater effectivity.

Conclusion: Current research provides the state-of-the-art of search of NEIs amongst three species by in-vitro assays which can be further utilized for bioactivity-guided isolations of such enzyme inhibitors. Further, it reports the optimized phyto-blend ratios so as to achieve synergistic anti-oxidative actions.

Summary: The current research work focuses on the optimization of the extraction process parameters and the ratios of phyto-synergistic blends of the leaves of three common medicinal plants viz. banyan, jamun and tulsi by chemometrics. Qualitative and quantitative chemo profiling of the extracts were done by different phytochemical tests and UV spectrophotometric methods. Enzymes like alpha amylase, alpha glucosidase, aldose reductase, dipeptidyl peptidase 4, angiotensin converting enzymes are found to be pathogenic in type 2 diabetes. In vitro screening of natural enzyme inhibitors amongst individual extracts and composite blends were carried out by different assay procedures and the potency expressed in terms of IC50 values. Antioxidant potentials were estimated by DPPH radical scavenging, ABTS, FRAP and Dot Blot assay. Hydroalcoholic solvent (50:50) gave maximal yield of bio-actives with minimal chlorophyll leaching. Hydroethanolic extract of tulsi showed maximal antioxidant effect. Though all composites showed synergism, maximal effects were shown by the composite (1:1:2) in terms of polyphenol yield, antioxidant effect and inhibitory actions against the targeted enzymes. Abbreviations used: DPP4- dipeptidyl peptidase 4; AR- aldose reductase; ACE- angiotensin converting enzyme; PPAR-γ- peroxisome proliferator activated receptor-γ; NEIs- natural enzyme inhibitors; BE- binding energy; GLP-1- Glucagon like peptide -1; ROS- Reactive oxygen species; CAT- catalase; GSH-Px- glutathione per-oxidase; SOD- superoxide dismutase; pNPG- para-nitro phenyl-α-D-gluco-pyranoside solution; DPPH- 1,1-diphenyl-2-picrylhydrazyl; RSM- Response surface methodology; CCD- central composite design; DMSO- dimethyl sulfoxide; HHL- hippuryl-L-histidyl-L-leucine; GPN-Tos- Gly-Pro p-nitroanilide toluenesulfonate salt; ESC- experimental scavenging capacity; TSC- theoretical scavenging capacity; FRAP- Ferric Reducing Assay Procedure; ABTS- 2, 2'- azinobis (3-ethylbenzothiazoline-6 - sulfonic acid.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0973-1296.172956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4787083PMC
October 2015

Computational pharmacokinetics and in vitro-in vivo correlation of anti-diabetic synergistic phyto-composite blend.

World J Diabetes 2015 Sep;6(11):1179-85

Baishakhi De, Koushik Bhandari, Nishant Chakravorty, Ranjan Mukherjee, Biswajoy Ghosh, Analava Mitra, School of Medical Science and Technology, IIT Kharagpur 721302, India.

Despite tremendous strides in modern medicine stringent control over insulin resistance or restoration of normoglycemia has not yet been achieved. With the growth of molecular biology, omics technologies, docking studies, and in silico pharmacology, modulators of enzymes and receptors affecting the molecular pathogenesis of the disease are being considered as the latest targets for anti-diabetic therapy. Therapeutic molecular targets are now being developed basing on the up or down regulation of different signaling pathways affecting the disease. Phytosynergistic anti-diabetic therapy is in vogue both with classical and non-classical medicinal systems. However its chemo-profiling, structural and pharmacokinetic validation awaits providing recognition to such formulations for international acceptance. Translational health research with its focus on benchside product development and its sequential transition to patient bedside puts the pharma RDs to a challenge to develop bio-waiver protocols. Pharmacokinetic simulation models and establishment of in vitro-in vivo correlation can help to replace in vivo bioavailability studies and provide means of quality control for scale up and post approval modification. This review attempts to bring different shades highlighting phyto-synergy, molecular targeting of antidiabetic agents via different signaling pathways and bio-waiver studies under a single umbrella.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4239/wjd.v6.i11.1179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564813PMC
September 2015

Docking Studies for Multi-Target Drugs.

Curr Drug Targets 2017 ;18(5):592-604

Federal University of Paraíba, Campus I, Joao Pessoa-PB, Brazil.

The most basic principle of drug action is found in the lock and key model, where the highest possible affinity for a target that also avoids side effects is desired. For many years this was understood as being "one drug, for one target, for one disease", however researchers began to observe that certain diseases are best treated with multi-target drugs. In recent years, studies have sought out polypharmacological compounds acting on multiple targets against complex (multifactorial) diseases, such as cancer, neurodegenerative disease, and certain infections. One of the computational tools used in research for multifunctional drugs is Molecular Docking. Through this methodology of Computer-Aided Drug Design, we observe complexes formed between ligands and interesting targets (often many), for a particular disease. This review reports on docking studies as used in investigations of new multi-target compounds; it also shows the various ways that such studies are used in the search for multifunctional compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1389450116666150825111818DOI Listing
September 2017

Editorial: in silico drug design and medicinal chemistry).

Authors:
Rajeev K Singla

Curr Top Med Chem 2015 ;15(11):971-2

SERB-Young Scientist/PI, Division of Biotechnology, Netaji Subhas Institute of Technology, Sec-3, Dwarka, New Delhi-110078, India.

Medicinal chemistry is not limited to molecules, their structures and design but also highly cohesive to pharmacological activities. The potency of a molecule varies by its structure. Hence structural activity relationship is the sub-branch which deals with the estimation of ability of a molecule in depicting any pharmacological activity. In silico drug design is a novel technique which is employed in designing a molecule by using computer aided software’s and bringing a superior and potent molecule. In recent years, in silico drug design has been merged with medicinal chemistry especially by the techniques like ligand based strategy to isolate the required structures. By such strategic techniques, there are high chances of delivering high throughput screening which involves of screening large number of molecules in a very less time. Involvement of such techniques would be a boon for development of new drug entity as it can aid in development of newer, safe, effective and potent drug molecules. Hence, the present issue is aimed to emphasize the cohesion between in silico drug design and it significance in medicinal chemistry. The articles which would be published will mainly focus on the role of in silico drug design techniques in the development of molecules to target various disease and disorders. Molecules can from natural/ synthetic/semi synthetic origin. Articles will be a treasure box consisting of employment of computational methods for unprecedented molecules. The issue will be sure an endorsement for international readership and researchers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/156802661511150408110453DOI Listing
May 2016
-->