Publications by authors named "Syed Ali Raza Naqvi"

47 Publications

Lu-DOTATATE Peptide Receptor Radionuclide Therapy: Indigenously Developed Freeze Dried Cold Kit and Biological Response in In-Vitro and In-Vivo Models.

Dose Response 2021 Jan-Mar;19(1):1559325821990147. Epub 2021 Feb 12.

Department of Chemistry, Government College University, Faisalabad, Pakistan.

Somatostatin receptors (SStR) based Lu-DOTATATE therapy is known as one of the highly effective neuroendocrine tumors (NETs) treatment strategy. Development of DOTATATE freeze-dried kit for imaging and therapy of SStR positive NETs is a prime goal in neuroendocrine cancer research. The present work describes the development of Lu-DOTATATE freeze dried cold kit for indigenous needs, through technology development fund (TDF) program offered by Higher Education Commission (HEC) Pakistan. The parameters for freeze dried kit production was optimized and tested the stored lyophilized cold kits for different time intervals after labeling with Lu radioisotope. The effect of ligand to radionuclide ratio, pH and reaction time at 90°C was recorded. Five times greater molar concentration of ligand, pH 5 and 30 min reaction time were the effective reaction conditions for maximum radiochemical yield. The radiolabeling yield at 1 day, 1-week and 4-week post storing period showed ∼100% radiochemical yield. The biodistribution study using rat model depicted the absence of non-targeted accumulation while glomerular filtration rate also explains the rapid renal washout. Cytotoxicity study showed quite favorable results for subjecting the radiopharmaceutical to clinical practice in Pakistan.
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http://dx.doi.org/10.1177/1559325821990147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883172PMC
February 2021

Antihypertensive and Antihyperlipidemic Activity of Aqueous Methanolic Extract of in Albino Rats.

Dose Response 2020 Jul-Sep;18(3):1559325820942077. Epub 2020 Jul 24.

Department of Eastern Medicine, Government College University, Faisalabad, Pakistan.

has a wide range of therapeutic effects so this study was planned to explore the antihypertensive and antihyperlipidemic therapeutic responses of doses using albino rats by measuring the blood pressure, biochemical parameters, and histological architecture of liver and kidney tissues. Thirty albino rats were divided into 5 groups (n = 6) as G1 (normal Control) received normal diet, G2 (positive control) received only 8% NaCl added diet (high salt diet); G3 was given atenolol (standard drug control) 50 mg/kg body weight, G4 and G5 groups were given methanolic plant extract as low dose (100 mg/kg body weight) and high dose (200 mg/Kg body weight) daily along with high salt diet for 4 weeks, respectively. significantly ( < .05) decreased the blood pressure in G4 and G5 groups as compared to G2 and G3. Significant ( < .05) impact was reported, on serum lipid profile and serum proteins as well as hepatoprotective and renoprotective potential on studying tissues sections under microscope, in animal groups given herbal extract as compared to control groups. It could be concluded that has therapeutic effect to manage the hypertension and hypercholesterolemia most probably via protecting the liver and renal architectures.
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http://dx.doi.org/10.1177/1559325820942077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383702PMC
July 2020

Synthesis, evaluation of thymidine phosphorylase and angiogenic inhibitory potential of ciprofloxacin analogues: Repositioning of ciprofloxacin from antibiotic to future anticancer drugs.

Bioorg Chem 2020 07 22;100:103876. Epub 2020 Apr 22.

Natural and Medical Sciences Research Center, University of Nizwa, Nizwa 611, Oman.

Over expression of thymidine phosphorylase (TP) in various human tumors compared to normal healthy tissue is associated with progression of cancer and proliferation. The 2-deoxy-d-ribose is the final product of thymidine phosphorylase (TP) catalyzed reaction. Both TP and 2-deoxy-d-ribose are known to promote unwanted angiogenesis in cancerous cells. Discovery of potent inhibitors of thymidine phosphorylase (TP) can offer appropriate approach in cancer treatment. A series of ciprofloxacin 2, 3a-3c, 4a-4d, 5a-5b, 6 and 7 has been synthesized and characterized using spectroscopic techniques. Afterwards, inhibitory potential of synthesized ciprofloxacin 2, 3a-3c, 4a-4d, 5a-5b, 6 and 7 against thymidine phosphorylase enzyme was assessed. Out of these twelve analogs of ciprofloxacin nine analogues 3a-3c, 4a-4c, 5a-5b and 6 showed good inhibitory activity against thymidine phosphorylase. Inhibitory activity as presented by their IC values was found in the range of 39.71 ± 1.13 to 161.89 ± 0.95 μM. The 7-deazaxanthine was used as a standard inhibitor with IC = 37.82 ± 0.93 μM. Furthermore, the chick chorionic allantoic membrane (CAM) assay was used to investigate anti-angiogenic activity of the most active ciprofloxacin-based inhibitor 3b. To enlighten the important binding interactions of ciprofloxacin derivatives with target enzyme, the structure activity relationship and molecular docking studies of chosen ciprofloxacin analogues was discussed. Docking studies revealed key π-π stacking, π-cation and hydrogen bonding interactions of ciprofloxacin analogues with active site residues of thymidine phosphorylase enzyme.
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http://dx.doi.org/10.1016/j.bioorg.2020.103876DOI Listing
July 2020

Dose-Dependent Internalization and Externalization Integrity Study of Newly Synthesized Tc-Thymoquinone Radiopharmaceutical as Cancer Theranostic Agent.

Dose Response 2020 Apr-Jun;18(2):1559325820914189. Epub 2020 Apr 23.

Isotope Production Division, Pakistan Institute of Nuclear Science and Technology, Nilore, Islamabad, Pakistan.

Thymoquinone (TQ) is a bioactive phytochemical isolated from and has been investigated for biochemical and biological activities in both in vitro and in vivo models. It is best known for its anticancer activities. Thymoquinone accomplishes anticancer activities through targeting multiple cancer markers including PPAR-γ, PTEN, P53, P73, STAT3, and generation of reactive oxygen species at the cancer cell surface. The radiolabeling of TQ with γ- and β-emitter radionuclide could be used as cancer diagnostic or therapeutic radiopharmaceutical, respectively. In this study, we are reporting the radiolabeling of TQ with technetium-99m (Tc), stability in saline and blood serum, internalization and externalization of Tc-TQ using rhabdomyosarcoma cancer cells line. The quality control study revealed more than 95% labeling yield and stable in blood serum up to 4 hours. In vitro internalization rate was recorded 27.08% ± 0.95% at 1 hour post 2 hours internalization period and comparatively slow externalization. The results of this study are quite encourging and could be investigated for further key preclinical parameters to enter phase I clinical trials.
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http://dx.doi.org/10.1177/1559325820914189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180313PMC
April 2020

Design and syntheses of 7-nitro-2-aryl-4-benzo[][1,3]oxazin-4-ones as potent anticancer and antioxidant agents.

J Mol Struct 2020 Aug 13;1214:128252. Epub 2020 Apr 13.

Interdisciplinary Research Center in Biomedical Materials, COMSATS University Islamabad, Lahore Campus, Lahore, 54000, Pakistan.

A group of new nitro substituted benzoxazinones () were synthesized from easily available 4-nitroanthranilic acid. All the synthesized compounds were characterized by FT-IR, H NMR, C NMR, mass spectrometry and elemental analysis. Anti-proliferative and pro-apoptotic potential of all the synthesized compounds () was evaluated by MTT and Hoechst 33258 staining assay respectively whereas their antioxidant properties were determined via DPPH free radical scavenging assay. The most active compounds (, and ) showed significant cytotoxic potential against HeLa cells with an inhibition of cell viability that ranged between 28.54 and 44.67% ( < 0.001). Albeit statistically different, the anti-proliferative effect of was in close match with that of the reference drug doxorubicin. Likewise, the test compounds showed profound pro-apoptotic potential with an apoptotic index that ranged between 52.86 and 75.61%. Besides, the docking studies revealed a higher efficiency for compounds ( and ) owing to their better affinity and inhibition constant (K = 4.397 and 3.713 nmol) respectively. The antioxidant potential of synthesized benzoxazinones () was in close agreement with the experimental anticancer results with a percent inhibition from 34.45 to 85.93% as compared to standard (90.56%).
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http://dx.doi.org/10.1016/j.molstruc.2020.128252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153534PMC
August 2020

Development of 99mTc-SDP-choline SPECT radiopharmaceutical for imaging of cerebrovascular diseases.

Pak J Pharm Sci 2020 Jan;33(1(Supplementary)):241-244

Pakistan Institute of Nuclear Science and Technology (PINSTECH), Nilore, Islamabad, Pakistan.

Cerebrovascular diseases are known as serious public health problem worldwide, which can be addressed more precisely through molecular imaging of non-functional brain cells. CDP-choline is an active cerebrovascular chemotherapeutic agent that can be used for diagnosis of cerebrovascular diseases post radiolabeling with γ-emitter radioisotopes. In this study we developed Tc labeled CDP-choline for imaging of cerebrovascular diseases particularly alzheimer, stroke, and parkinson's diseases. The radiosynthesis reaction resulted 97.47±2.34% radiochemical with promising stability, that is, >95% up to 6 h in blood serum. The biodistribution study in healthy mice revealed non-accumulated uptake of radiochemical in key body organs; in brain it was 8.59±1.11% ID/g at 1h post-injection which washed-out leaving behind 0.87±0.61% ID/g at 24 h post-injection. The over-all data revealed the Tc-CDP-choline could be a good candidate for further imaging investigations in diseased animal model.
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January 2020

Antimicrobial and Antihypercholesterolemic Activities of .

Dose Response 2020 Jan-Mar;18(1):1559325820904858. Epub 2020 Feb 4.

Department of Eastern Medicine, Government College University Faisalabad, Pakistan.

Multidrug resistance has increased globally in the communities. Bacterial infections associated with health care have weakened the existing antimicrobial therapy and demand the search for alternative therapies. In the present investigation, the medicinal plant from Quetta, Pakistan, has been screened for antimicrobial potential. In vitro antimicrobial efficacy of extracts (methanol and ethanol) was quantitatively evaluated on the basis of zone of inhibition against different bacteria and minimum inhibitory concentration (MIC). In vivo, antihypercholesterolemic activity is determined in different rat groups. The results of the study indicated that the ethanol extract of showed maximum zone of inhibition for of 12.1 ± 1.1 mm from all others. The methanol extract showed maximum zone of inhibition for of 11.9 ± 1.0 mm and rifampicin showed maximum zone of inhibition of 23.1 ± 0.9 mm. The results of ethanol and methanol extract of against different bacteria revealed that this plant has greater antimicrobial activity. However, the plant extract shows nonsignificant antihypercholesterolemic activity. The extract of this plant can be utilized as medicine to inhibit several infections caused by some bacterial pathogens found in human body.
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http://dx.doi.org/10.1177/1559325820904858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000860PMC
February 2020

Purification and modification of Cordia myxa gum to enhance its nutraceutical attribute as binding agent.

Pak J Pharm Sci 2019 Sep;32(5(Supplementary)):2245-2250

Department of Chemistry, Government College University, Faisalabad, Pakistan.

The aim of the present study was to purify, hydrolyze and modify the Cordia myxa gum to document its binder potential in pharmaceutical tablets formulation. The hydrolysis and modification was carried out to remove impurities, roughness, increase thermal stability and to improve the functional properties of biopolymers. Physiochemical properties such as pH, solubility, viscosity, swelling index, bulk and tapped density was performed prior to investigate binder potential. The binder potential of Cordia myxa gum was studied in its different forms such as crude, purified, modified and hydrolyzed in paracetamol tablets and was compared with standard hydroxypropyl methylcellulose (HPMC) being used as synthetic binder. Tablets were prepared by direct compression method and evaluated for weight uniformity, hardness, friability, disintegration time and dissolution analysis. Prepared tablets with selected gums exhibit faster and slower dissolution profile in the same dissolution system. The crude gum has high dissolution rate whereas the hydrolyzed and modified gums showed less dissolution rate. The hydrolyzed and modified gums having faster release rate and it could be helpful in conventional tablet formulations efficiently as compared to synthetic HPMC binder.
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September 2019

Detection of Paracetamol as substrate of the gut microbiome.

Pak J Pharm Sci 2019 Mar;32(2 (Supplementary)):751-757

Biomedical Research Center, Qatar University, Qatar.

Gut microbiome, a new organ; represent targets to alter pharmacokinetics of orally administered drugs. Recently, in vitro trials endorsed the idea that orally administered drugs interact and some of their quantity may be taken up by normal microbiome during transit through gut. Such transport mechanisms in microbiome may compete for drug with the host itself. Currently, no data confirms specific transport system for paracetamol uptake by gut microbiome. In vivo trial was conducted in normal healthy male rats (n=36). Paracetamol was administered orally in a single dose of 75mg/kg to isolate microbial mass after transit of 2, 3, 4, 5 and 6 hours post drug administration. Paracetamol absorbance by microbiome was pursued by injecting extracted microbial lysate in RP-HPLC-UV with C18 column under isocratic conditions at 207nm using acetonitrile and water (25:75 v/v) pH 2.50 as mobile phase. Paracetamol absorbance (14.10±0.75μg/mg of microbial mass) and percent dose recovery (13.16±0.55%) seen at transit of 4 hours was significantly higher (P<0.05) compared to other groups. Study confirms the hypothesis of homology between membrane transporters of the gut microbiome and intestinal epithelium. Orally administered drugs can be absorbed by gut microbes competitively during transit in small intestine and it varies at various transit times.
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March 2019

225Ac Prostate-Specific Membrane Antigen Posttherapy α Imaging: Comparing 2 and 3 Photopeaks.

Clin Nucl Med 2019 May;44(5):401-403

Government College University, Faisalabad, Pakistan.

Ac-based PSMA-targeted therapy has emerged as promising agent for the treatment of metastatic castration-resistant prostate cancer. Posttherapy image is used for tracer localization and dosimetry. Prior 2 photopeaks of 440 and 218 KeV were reported for posttherapy imaging. Our study of gamma ray spectrum, phantom, and clinical images show that imaging with 3 major photopeaks of 78, 218, and 440 KeV gives better quality images, high count statistics, and higher number of lesion delineations. It is therefore suggested that posttherapy imaging may be carried out using 3 major abundant photopeaks.
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http://dx.doi.org/10.1097/RLU.0000000000002525DOI Listing
May 2019

Technetium-99m labeled Ibuprofen: Development and biological evaluation using sterile inflammation induced animal models.

Mol Biol Rep 2019 Jun 30;46(3):3093-3100. Epub 2019 Mar 30.

Department of Chemistry, Government College University Faisalabad, Faisalabad, 38000, Pakistan.

In this study we are presenting the development of technetium-99m (Tc) labeled ibuprofen for the imaging of aseptic inflammation. Tc-Ibuprofen complex was developed by optimizing the radiolabeling conditions such as reaction time, ligand and reducing agent concentration, pH, reaction time and temperature. Following the addition of 600 µg of ibuprofen, 4 µg of stannous chloride as reducing agent and 300 MBq Tc radioactivity; the pH of reaction mixture was adjusted to 11 and allowed to react for 15 min at room temperature. Chromatography analysis revealed > 94% Tc-ibuprofen complex formation with promising stability in saline and blood serum up to 6 h. Biodistribution study using normal and sterile inflammation induced mice indicated low accumulation of labeled compound in key body organs; however, kidneys (14.76 ± 0.87% ID/g organ) and bladder (31.6 ± 3.0% ID/g organ) showed comparatively higher radioactivity due to main excretory path. Inflamed to normal tissues ratio (T/NT), at 1 h post-injection, showed promising value (4.57 ± 0.56). The SPECT imaging of artificially inflammation induced rabbit model also verified the biodistribution results. In conclusion, radiochemical purity and biological evaluation of Tc-ibuprofen complex indicates the agent can be utilized for imaging of deep seated aseptic inflammation.
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http://dx.doi.org/10.1007/s11033-019-04762-2DOI Listing
June 2019

5-Endo-dig cyclizations in organic syntheses.

Mol Divers 2020 Feb 5;24(1):295-317. Epub 2019 Mar 5.

Department of Chemistry, Faculty of Physical Sciences, Government College University, Faisalabad, 38000, Pakistan.

The favorability of ring closure reactions as per Baldwin rules has gained immense importance recently. This is evident from the current literature such as research articles, reviews, and books that have been published in this area. This review covers the recent applications of 5-endo-dig cyclization in organic synthesis focusing in the last two decades. A variety of 5-membered heterocycles as well as carbocycles could be synthesized via 5-endo-dig cyclization reactions. The important applications of 5-endo-dig cyclization in organic synthesis covering different aspects have been summarized in this review.
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http://dx.doi.org/10.1007/s11030-019-09930-xDOI Listing
February 2020

Magneto-Priming Improved Nutraceutical Potential and Antimicrobial Activity of Momordica charantia L. Without Affecting Nutritive Value.

Appl Biochem Biotechnol 2019 Jul 7;188(3):878-892. Epub 2019 Feb 7.

Department of Chemistry, Government College University, Faisalabad, 38000, Pakistan.

The need for some economic strategies for increased growth and nutraceuticals of medicinal plants is well acknowledged now. It was hypothesized that external magnetic field treatment (MFT) of seeds affecting internal magnet of cells may affect growth and metabolism. In this study, seeds were subjected to pre-sowing magnetic field (50 mT at 5 mm for 5 s). At vegetative stage, the leaf growth, chlorophyll content, catalase (CAT), peroxidase (POD), amino acids, proteins, flavonoids, soluble sugars, total soluble phenolics, carotenoids, anthocyanins, phenolic profile (HPLC based), and antimicrobial activity of leaves (in terms of the minimum inhibitory concentration against Staphylococcus aureus and Pseudomonas aeruginosa) were studied. Yield was evaluated for nutritive components in fruit (peel+pulp) and peel. MFT improved germination percentage, growth, leaf chlorophyll, antimicrobial activity, peel amino acids, phenolics, and POD with negligible effect on fruit nutritive value. Moreover, photosynthetic pigments and cinnamic acid exhibited direct correlation with antimicrobial potential against both pathogens. However, sinapic acid showed positive correlation against Staphylococcus aureus only. Cinnamic acid, coumaric acid, syringic acid, and quercetin were in direct correlation against Pseudomonas aeruginosa; it was directly correlated with total flavonoids too. In conclusion, magnetic field can be used to manipulate plant cell metabolism promising improvement of growth, antimicrobial activity, and phenolics of interest.
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http://dx.doi.org/10.1007/s12010-019-02955-wDOI Listing
July 2019

Identification of 1,2,4-triazoles as new thymidine phosphorylase inhibitors: Future anti-tumor drugs.

Bioorg Chem 2019 04 4;85:209-220. Epub 2019 Jan 4.

Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, 30-688 Cracow, Medyczna 9, Poland.

Thymidine phosphorylase (TP) is over expressed in several solid tumors and its inhibition can offer unique target suitable for drug discovery in cancer. A series of 1,2,4-triazoles 3a-3l has been synthesized in good yields and subsequently inhibitory potential of synthesized triazoles 3a-3l against thymidine phosphorylase enzyme was evaluated. Out of these twelve analogs five analogues 3b, 3c, 3f, 3l and 3l exhibited a good inhibitory potential against thymidine phosphorylase. Inhibitory potential in term of IC values were found in the range of 61.98 ± 0.43 to 273.43 ± 0.96 μM and 7-Deazaxanthine was taken as a standard inhibitor with IC = 38.68 ± 4.42 μM. Encouraged by these results, more analogues 1,2,4-triazole-3-mercaptocarboxylic acids 4a-4g were synthesized and their inhibitory potential against thymidine phosphorylase was evaluated. In this series, six analogues 4b-4g exhibited a good inhibitory potential in the range of 43.86 ± 1.11-163.43 ± 2.03 μM. Angiogenic response of 1,2,4-triazole acid 4d was estimated using the chick chorionic allantoic membrane (CAM) assay. In the light of these findings, structure activity relationship and molecular docking studies of selected triazoles to determine the key binding interactions was discussed. Docking studies demonstrate that synthesized analogues interacted with active site residues of thymidine phosphorylase enzyme through π-π stacking, thiolate and hydrogen bonding interactions.
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http://dx.doi.org/10.1016/j.bioorg.2019.01.005DOI Listing
April 2019

Phenolic acid profiling and antiglycation studies of leaf and fruit extracts of tyrosine primed Momordica charantia seeds for possible treatment of diabetes mellitus.

Pak J Pharm Sci 2018 Nov;31(6 (Supplementary):2667-2672

Department of Botany, Government College University, Faisalabad, Pakistan.

The increasing risk of variety of fatal diseases including diabetes mellitus is imposing serious challenge to chemist, biologists and clinicians. Due to the side effects of the chemotherapy, worldwide it is thinking that phyto-medicine are more effective to cope continuously increasing risk of fatal diseases without any side effect. Seed priming is a strategic pre-sowing semi-bioengineering technique which has ability to improve the growth rate and biologically active compounds in short time. Among seed priming techniques, tyrosine seed priming most frequently used because amino acids provide best growth media for nutritional food crops. Seeds of Momordica charantia were subjected to the pre-sowing tyrosine solution. Different growth parameters including growth emergence rate, seedling vigor, growth and weight of root, shoot and leaf were studied. The results showed positive effect on Momordica charantia seed growth and phenolic acids production i.e. ferulic acid - 43.95 ppm and sinapic acid - 18.39 ppm. The antiglycation assay showed 23.45±1.23% antiglycation activity of primed-seed fruit extract as compare to control seed fruit extract (0.87±0.03%). On the basis of the results, it is concluded that tyrosine primed seed fruit extract could effectively be further tested for pre-clinical and clinical studies to manage diabetes mellitus disease.
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November 2018

Enzymatic degradation study of 111In-labeled minigastrin peptides using cathepsin B enzyme and AR42J cancer cell line for the development of neuroendocrine tumor imaging radiopharmaceuticals.

Pak J Pharm Sci 2018 Nov;31(6 (Supplementary):2585-2589

Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan.

Neuroendocrine tumors (NET) are the rare tumors which often impose graveyard threat. These tumors are characterized by the over expression of various G-protein coupled receptors including cholecystokinin (CCK) receptors-1 and 2 (A or B). Minigastrin peptides are being investigated for theranostic purposes of CCK-2 receptor positive NET. The minigastrin analogue (APHO70) was modified by engineering enzyme susceptible tetrapeptide sequence into APHO70 peptide to reduce the random degradation by lysosome enzymes which pave the way to random trafficking in patient's body and dipeptide addition at c-terminus. All the four modified minigastrin peptides (MG-CL1-4) were investigated for lysosome cathepsin B (catB) enzyme susceptibility and fate into AR42J cancer cell line. The indium-111 labeled MG-CL1-4 peptides were also studied for target (tumor) and non-target saccumulation by using tumor induced mice. The RP-HPLC analysis result showed nonspecific cleavage of standard 111In-APH070 and 111In-MGCL1 while specific cleavage was noted in case of 111In-MGCL (2-4). The effect of specific and non-specific cleavage on biodistribution in tumor induced nude mice model indicates the promising accumulation of 111In-MGCL2, 111In-MGCL3, and 111In-MGCL4 radiotracers while 111In-MGCL1 showed less accumulation. 111In-MGCL2 and 111In-MGCL3 showed highest target-to-kidney ratio (T/K) i.e. 1.71 and 1.72, respectively whereas standard compound showed T/K 1.13. In conclusion, the two indium-111 labeled analogues i.e. 111In-MGCL2 and 111In-MGCL3 showed promising sensitivity for tumor andcould be tested for further investigation to reach pre-clinical studies.
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November 2018

Susceptibility of Tc-Ciprofloxacin for Common Infection Causing Bacterial Strains Isolated from Clinical Samples: an In Vitro and In Vivo Study.

Appl Biochem Biotechnol 2019 Jun 5;188(2):424-435. Epub 2018 Dec 5.

Department of Chemistry, Government College University, New Campus, Faisalabad, 38000, Pakistan.

Tc-ciprofloxacin scintigraphy is useful in the detection of gram-positive and gram-negative bacterial infections and also for differentiating the infection from aseptic inflammation. However, due to growing bacterial resistance to antibiotics, the Tc-ciprofloxacin no longer can be effective in broad-spectrum infection imaging as it is gradually losing specificity. In this study, we are presenting our findings regarding the in vitro and in vivo susceptibility of Tc-ciprofloxacin for multi-drug-resistant Staphylococcus aurous, Escherichia coli, and Pseudomonas aeruginosa bacterial strains which were isolated from clinical samples. The results of radiosynthesis of Tc-ciprofloxacin showed more the 95% radiochemical purity and less than 5% radioactive impurities. In vitro Tc-ciprofloxacin susceptibility test showed that E. coli offered more resistant to Tc-ciprofloxacin as compared to S. aurous and P. aeruginosa. In vivo study using bacterial infection induced rabbit model also revealed lowest uptake by E. coli lesion. The T/NT values were obtained 1.96 ± 0.15 in the case of E. coli; 2.81 ± 0.51 in the case of S. aurous; and 2.32 ± 0.66 in the case of P. aeruginosa at 4 h post-injection. The SPECT infection imaging of S. aurous, E. coli, and P. aeruginosa bacterial infection induced rabbit models also indicated the clear accumulation in S. aurous and P. aeruginosa lesions while negligible uptake by E. coli lesion further verify the in vitro and in vivo susceptibility profile. On the bases of the results obtained, the Tc-ciprofloxacin showed selective and poor broad spectrum SPECT infection imaging.
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http://dx.doi.org/10.1007/s12010-018-2915-zDOI Listing
June 2019

Technetium-99m radiolabeling and biological study of epirubicin for in vivo imaging of multi-drug-resistant Staphylococcus aureus infections via single photon emission computed tomography.

Chem Biol Drug Des 2019 02 31;93(2):154-162. Epub 2018 Oct 31.

Department of Chemistry, Government College University, Faisalabad, Pakistan.

The development of functional imaging is a promising strategy for diagnosis and treatment of infectious and cancerous diseases. In this study, epirubicin was developed as a [ Tc]-labeled radiopharmaceutical for the imaging of multi-drug-resistant Staphylococcus aureus infections. The labeling was carried out using sodium pertechnetate (Na TcO ; ~370 MBq). The other parameters such as amount of ligand, reducing agent (SnCl .2H O), and pH were optimized. The highest labeling yield ≥96.98% was achieved when 0.3 mg epirubicin, 13 μg SnCl .2H O, and ~370 MBq Na TcO were incubated at pH 7 for 15 min in the presence of ascorbic acid at room temperature. Radiochemical purity, stability, charge, and glomerular filtration rate were studied to evaluate the biological compatibility for in vivo administration. Biodistribution investigations showed radiotracer uptake (13.89 ± 1.56% ID/gm organ) by liver and 7.79 ± 0.38% ID/gm organ by kidneys at 30 min post-injection which promisingly wash out at 24 hr post-injection. Scintigraphy study showed selective uptake in S. aureus-infected tissues in contrast to turpentine oil-induced inflamed tissues. Target-to-non-target ratio (6.7 ± 0.05) was calculated at 1 hr post-injection using SPECT gamma camera. The results of this study reveal that the [ Tc]-epirubicin can be a choice of imaging and monitoring the treatment process of multi-drug resistant S. aureus bacterial infections.
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http://dx.doi.org/10.1111/cbdd.13393DOI Listing
February 2019

Synthetic applications and methodology development of Chan-Lam coupling: a review.

Mol Divers 2019 Feb 30;23(1):215-259. Epub 2018 Aug 30.

Department of Chemistry, Government College University Faisalabad, Faisalabad, 38000, Pakistan.

Chan-Lam coupling is one of the most popular and easy methods to perform arylation of amines (N-arylations). This cross-coupling is generally performed by reacting aryl boronate derivatives with a variety of substrates involving nitrogen containing functional groups such as amines, amides, ureas, hydrazine, carbamates. This article summarizes the synthetic applications of this reaction and the efforts of scientists to develop novel and efficient methodologies for this reaction.
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http://dx.doi.org/10.1007/s11030-018-9870-zDOI Listing
February 2019

Lu-DOTA-coupled minigastrin peptides: promising theranostic agents in neuroendocrine cancers.

Mol Biol Rep 2018 Dec 24;45(6):1759-1767. Epub 2018 Aug 24.

Department of Chemistry, Government College University, Faisalabad, 38000, Pakistan.

Treatment with radionuclide labeled regulatory peptides is a promising tool in the management of patients with inoperable receptor positive neuroendocrine tumors. Peptide receptor lutetium-177 radionuclide therapy currently has gained ample attention due to high specific accumulation of regulatory peptides at tumor cell surface and promising characteristics of β- and γ-energy photons of lutetium-177 radionuclide. In this study gastrin peptides analogues were labeled with lutetium-177 by subsequent mixing of LuCl (~ 185 MBq), ammonium acetate buffer of 5 pH, gentistic acid, aqueous solution of gastrin peptide analogues (1 mg/mL) and heating the reaction mixture at 98 °C which resulted in high radiochemical yield (> 96%). Chromatographic analysis was carried out to analyze the radiochemical purity. The shelf life and serum stability results showed the labeled peptides are sufficiently stable up to 4-h. Glomerular filtration rate study results showed moderate filtration through kidneys. The GFR values of Lu-MGCL2 and Lu-MGCL4 was noted 48 mL/min and 45 mL/min, respectively. Biodistribution and scintigraphy study using rat and rabbit models showed minimal non-target accumulation, moderate uptake by liver and kidneys. The promising radiochemical yield, stability, GFR values and biodistribution results of Lu-MGCL2 & 4 indicate, the agents can be tested clinically for PRRT procedures.
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http://dx.doi.org/10.1007/s11033-018-4319-0DOI Listing
December 2018

Post interferon therapy decreases male fertility through gonadotoxic effect.

Pak J Pharm Sci 2018 Jul;31(4(Supplementary)):1565-1570

Department of Microbiology, University of the Punjab, Lahore, Pakistan.

Prevalence of hepatitis C virus (HCV) has been seen in more than 15% of Pakistani population. For the treatment of this infection, only two medicines, interferon, and ribavirin were approved in 1998. The concerned physicians evaluate side effects of these two antiviral drugs only during the treatment period. The long-term extra hepatic side effects are being neglected. This retrospective study was conducted with reference to induced infertility in HCV treated 40 male patients from the period 2008-2015. Possible effects of interferon therapy on fertility hormones and seminal parameters were assessed. Level of fertility hormones like serum Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), and testosterone was measured. For seminal parameters, guidelines from World Health Organization (WHO) were followed. Among forty cases of HCV patients who received interferon, only 14 (35%) have children and 26 (65%) could not conceive (p = 0.0372). After HCV treatment, HCV positive patients showed a significant change in the level of FSH, LH (p<0.05). Especially, it decreased testosterone level (p=0.0096). Similarly, HCV treatment significantly decreased sperm count (p=0.001) and motility (p=0.0005).
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July 2018

Evaluation of 99mTc-sulfadiazine as Bacillus microorganisms infection imaging agent using animal model.

Pak J Pharm Sci 2018 Jul;31(4(Supplementary)):1495-1499

Department of Chemistry, Government College University, Faisalabad, Pakistan.

Bacterial infection is one of the vital sources of morbidity and mortality. The development of single photon emission computed tomography (SPECT) radiotracer agents using antibiotics, for targeting in-vivo bacteria, helps in antibiotic dose calibration, targeted infection therapy and reduction in mortality rate. The aim of this study was to appraised Tc-labeling sulfadiazine as a radiopharmaceutical for bacillus infections imaging. Radiolabeling of sulfadiazine with technetium-99m was carried out by subsequent addition of 1.5 mL aqueous solution of sulfadiazine (1mg/mL), 120µg stannous tartrate, gentistic acid as stabilizing agent and 185 MBq normal saline solution of TcO- (pertechnetate) at pH = 5. The reaction mixture was incubated for 40 min at room temperature with light stirring. The quality control analysis (ITLC-SG and paper chromatography analysis) revealed ~ 98% labeling yield. Biodistribution and scintigraphic study was carried using bacillus bacterial infection induced New Zealand white rabbits. Due to the ease of Tc-sulfadiazine conjugation method, high labeling efficiency, shelf stability (>95% up to 6h), blood serum stability (~90% up to 6h) and high uptake in the infected muscle (T/NT =2.21 at H), Tc-SDZ could be used as radiopharmaceutical of choice for further pre-clinical and clinical studies.
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July 2018

Ciprofloxacin: from infection therapy to molecular imaging.

Mol Biol Rep 2018 Oct 4;45(5):1457-1468. Epub 2018 Jul 4.

State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, E-208 West Campus, 2 Ling Gong Rd., Dalian, 116024, China.

Diagnosis of deep-seated bacterial infection remains a serious medical challenge. The situation is becoming more severe with the increasing prevalence of bacteria that are resistant to multiple antibiotic classes. Early efforts to develop imaging agents for infection, such as technetium-99m (Tc) labeled leukocytes, were encouraging, but they failed to differentiate between bacterial infection and sterile inflammation. Other diagnostic techniques, such as ultrasonography, magnetic resonance imaging, and computed tomography, also fail to distinguish between bacterial infection and sterile inflammation. In an attempt to bypass these problems, the potent, broad-spectrum antibiotic ciprofloxacin was labeled with Tc to image bacterial infection. Initial results were encouraging, but excitement declined when controversial results were reported. Subsequent radiolabeling of ciprofloxacin with Tc using tricarbonyl and nitrido core, fluorine and rhenium couldn't produce robust infection imaging agent and remained in discussion. The issue of developing a robust probe can be approached by reviewing the broad-spectrum activity of ciprofloxacin, labeling strategies, potential for imaging infection, and structure-activity (specificity) relationships. In this review we discuss ways to accelerate efforts to improve the specificity of ciprofloxacin-based imaging.
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http://dx.doi.org/10.1007/s11033-018-4220-xDOI Listing
October 2018

Nucleophilic ring opening reactions of aziridines.

Mol Divers 2018 May 4;22(2):447-501. Epub 2018 May 4.

Department of Chemistry, Government College University Faisalabad, Faisalabad, 38000, Pakistan.

Aziridine ring opening reactions have gained tremendous importance in the synthesis of nitrogen containing biologically active molecules. During recent years, a great effort has been put forward by scientists toward unique bond construction methodologies via ring opening of aziridines. In this regard, a wide range of chiral metal- and organo-catalyzed desymmetrization reactions of aziridines have been reported with carbon, sulfur, oxygen, nitrogen, halogen, and other nucleophiles. In this review, an outline of methodologies adopted by a number of scientists during 2013-2017 for aziridine ring opening reactions as well as their synthetic applications is described.
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http://dx.doi.org/10.1007/s11030-018-9829-0DOI Listing
May 2018

Biosurfactants production potential of native strains of Bacillus cereus and their antimicrobial, cytotoxic and antioxidant activities.

Pak J Pharm Sci 2018 Jan;31(1(Suppl.)):251-256

Department of Microbiology, Government College University, Faisalabad, Pakistan.

Present study was designed to evaluate the biosurfactant production potential by native strains of Bacillus cereus as well as determine their antimicrobial and antioxidant activities. The strains isolated from garden soil were characterized as B. cereus MMIC 1, MMIC 2 and MMIC 3. Biosurfactants were extracted as grey white precipitates. Optimum conditions for biosurfactant production were 37°C, the 7th day of incubation, 0.5% NaCl, pH 7.0. Moreover, corn steep liquor was the best carbon source. Biuret test, Thin Layer Chromatography (TLC), agar double diffusion and Fourier Transform Infrared Spectroscopy (FTIR) characterized the biosurfactants as cationic lipopeptides. Biosurfactants exhibited significant antibacterial and antifungal activity against S. aureus, E. coli, P. aeruginosa, K. pneumoniae, A. niger and C. albicans at 30 mg/ml. Moreover, they also possessed antiviral activity against NDV at 10 mg/ml. Cytotoxicity assay in BHK-21 cell lines revealed 63% cell survival at 10 mg/ml of biosurfactants and thus considered as safe. They also showed very good antioxidant activity by ferric-reducing activity and DPPH scavenging activity at 2 mg/ml. Consequently, the study offers an insight for the exploration of new bioactive molecules from the soil. It was concluded that lipopeptide biosurfactants produced from native strains of B. cereus may be recommended as safe antimicrobial, emulsifier and antioxidant agent.
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January 2018

Radiolabeling of benzylpenicillin with lutetium-177: Quality control and biodistribution study to develop theranostic infection imaging agent.

Pak J Pharm Sci 2017 Nov;30(6(Supplementary)):2349-2354

Institute of Nuclear Medicine Oncology and Radiotherapy (INOR), Abbottabad, Pakistan.

Benzylpenicillin acts through binding with beta-lactamase enzyme and inhibiting the bacterial cell wall biosynthesis. Therefore, the radiolabeling of benzylpenicillin with lutetium-177 is expected to serve as a theranostic agent for deep-seated bacterial infections. The radiolabeling of benzylpenicillin resulted ~93% radiochemical yield at optimized reaction conditions. Radiochemical purity analysis was tested with the help of Whatman No. 2 paper and instant thin layer chromatography. Biodistribution study with healthy New Zeeland white rabbit revealed moderate accumulation in different organs. Kidneys are the major organs, showed not more than 4.57±0.89% injected dose per gram organ (ID/gm organ) at 1 h time point and 3.48±1.11% ID/gm organ at 6 h time point. The accumulation of tracer agent in liver was found in the range of 7.42±2.42% to 9.09±2.76 ID/gm organ. The glomerular filtration rate studies revealed rapid clearance - omitting the chance of nephrotoxicity. The radiolabeling yield, biodistribution and glomerular filtration rate results revealed 177Lu-benzylpencillin could be a potential candidate to diagnose the deep-seated bacterial infection.
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November 2017

Recent trends in ring opening of epoxides with sulfur nucleophiles.

Mol Divers 2018 Feb 14;22(1):191-205. Epub 2017 Nov 14.

Department of Chemistry, Government College University Faisalabad, Faisalabad, 38000, Pakistan.

Thiolysis of epoxides offers an efficient and simple synthetic approach to access [Formula: see text]-hydroxy sulfides which are valuable scaffold in the synthesis of various important molecules in medicinal chemistry. This review article presents a recent compilation of the synthetic approaches developed after 2000 for the thiolysis of epoxides.
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http://dx.doi.org/10.1007/s11030-017-9796-xDOI Listing
February 2018

Designing and molecular docking of cyclic peptides against HCV NS3 protease.

Pak J Pharm Sci 2017 Sep;30(5(Supplementary)):1965-1969

Department of Bioinformatics and Biotechnology, Government College University (GCU), Faisalabad, Pakistan.

Hepatitis C Virus (HCV) infection is a worldwide serious health issue which contributes towards most of the hepatic morbidities. So far no prophylaxis is available to prevent this virus; therefore, development of antiviral compounds to fight HCV infection is the need of time. Chemically synthesized peptides that are potent immunogenic antigens are being pursued as candidate vaccines against HCV. The present study was planned to identify peptide inhibitors having potential to block the activity of NS3 protein of HCV that will ultimately arrest HCV multiplication. Docking of NS3 with peptides revealed that the majority of the peptides have strong binding affinity for active sites of NS3. Peptide 1, 2, 3 and 6 were found interactive with NS3 active residues while the active sites of NS3 had hydrophobic contact with the rest of peptides. Thus, these peptides bear therapeutic potential of a candidate drug for the prevention of HCV replication. Post docking analysis revealed important binding abilities of peptides with the active sites of NS3 protein, showing the efficiency of peptides as potential peptide inhibitors against HCV. The study revealed that HCV replication can be inhibited by these peptides. HCV replication inhibition potential of these peptides can contribute in reducing the burden of HCV infection and its associated complications worldwide.
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September 2017