International journal of pharmacy and pharmaceutical sciences/International Journal of Pharmacy and Pharmaceutical Sciences, Apr 1, 2024
Objective: Universal use of antibacterial agents and swift development of resistance by the micro... more Objective: Universal use of antibacterial agents and swift development of resistance by the microorganisms pose a major threat to public health. Hence, there is a pressing need to develop novel antimicrobials. Isoxazole derivatives exhibiting versatile biological activities have been widely used as important scaffolds in the field of drug designing. Methods: Twenty isoxazole derivatives were virtually screened by means of the molecular docking approach in order to identify potential antimicrobials against the most common disease-causing bacteria, S. aureus. In silico studies were done to detect the selectivity of the novel isoxazole derivatives for the selected bacterial protein targets using 'Glide'. In silico docking was carried out on few essential enzymes of S. aureus; Dihydrofolate reductase (DHFR), DNA gyrase, Dihydropteroate Synthetase (DHPS), Pyuvate kinase (PK). The compounds were subjected to energy minimization, followed by optimization and minimization of protein and generation of 3D grid at its active site. The ligands were subjected to molecular docking the Standard Precision and Extra Precision modes. Results: Docking of the compounds with Pyruvate Kinase and dihydrofolate reductase are quite encouraging.2C (4-hydroxy) and 2D (4-hydroxy) analogues gavea G Score of-8.33 and-8.64 with DHFR and Pyruvate Kinase respectively. However, the dock scores for the other target proteins indicate that the scaffolds have not bound with those bacterial targets. Moreover, ADME studies indicate that the derivatives do not show any violations in the rules for the requirements of orally active drugs. Conclusion: Study suggests that the derivatives 2C (4-hydroxy) and 2D(2-hydroxy) specifically bind to the active site of PK and DHFR. In silico ADME studies predicted the compounds to be "drug-like." Hence the hydroxy derivatives may be considered as leads for further structural modifications to arrive at potential anti-bacterial agents.
International Journal of Current Pharmaceutical Research, Jul 15, 2022
Objective: The present work discusses developing a novel method for estimation of residual solven... more Objective: The present work discusses developing a novel method for estimation of residual solvents in Gliclazide using Gas chromatography and determining its consistency, reliability and reproducibility by performing its validation. Methods: A Gas chromatograph equipped with aflame ionization detector, column DB-624 (60 m x 0.32 mm x 1.8 µm) with Nitrogen as carrier gas was used and the column temperature was 40 °C (hold for 15 min) and increased to 240 °C at 20 °C per min. The solutions were prepared using-Methyl-2-Pyrrolidone (NMP) diluent as per the procedure given in protocol and appropriately injected as per the sequence. The validation parameters checked were System suitability, Specificity, Linearity and Range, Accuracy, Precision, Limit of detection, Limit of quantitation, Ruggedness and Robustness. Results: The data for each validation parameter tested is compiled and documented. It was found that the results obtained for each parameter compiled with their given acceptance criteria. Hence, the developed method was considered reproducible, reliable and consistent. Conclusion: The method of analysis complies with all the parameters tested and it was found to be reliable, consistent and reproducible.
International Journal of Pharmacy and Pharmaceutical Sciences, Aug 1, 2022
Objective: The present study discusses molecular docking of some novel coumarin-benzothiazole Sch... more Objective: The present study discusses molecular docking of some novel coumarin-benzothiazole Schiff bases and the prediction of pharmacokinetic properties of potent molecules by the computational method. Methods: Five protein targets were selected for the study and their structures were taken from RCSB Protein Data Bank in PDB format. Preparation of proteins was done using Discovery Studio 2021 Client. A total of twenty derivatives were drawn using ChemDraw 20.0 and saved in Mol format. Molecular docking was performed using PyRx software. Docking results were visualized by Discovery Studio 2021 Client. The pharmacokinetic properties of the best compounds were determined using the pkCSM tool. Results: All twenty derivatives were docked against the five proteins, namely DNA Ligase (PDB ID: 3PN1), Topoisomerase (PDB ID: 3TTZ), Sterol demethylase (PDB ID: 5FSA), Enoyl-acyl-carrier protein (PDB ID: 1BVR) and Glutamate racemase (PDB ID: 5HJ7). The compound JJB18 has shown the best binding score against DNA ligase (-10.7 kcal/mol), Glutamate racemase (-8.4 kcal/mol), and Enoyl-acyl-carrier protein (-10.8 kcal/mol). Further, compound JJB19 has shown the best score for fungal sterol demethylase (-10.6 kcal/mol) and compound JJB20 towards topoisomerase (-9.4 kcal/mol) than the standard drugs. The physicochemical properties of potent derivatives were also reported. Conclusion: Molecular Docking study indicates that coumarin-benzothiazole Schiff bases may be effective inhibitors for the different microbial proteins. Additionally, in silico ADMET studies predicts drug-like features. Hence, these compounds may be considered lead molecules and further investigation of their analogues may help in the development of novel drugs for the treatment of microbial diseases.
International Journal of Pharmacy and Pharmaceutical Sciences
Objective: The present study discusses molecular docking of some novel coumarin–benzothiazole Sch... more Objective: The present study discusses molecular docking of some novel coumarin–benzothiazole Schiff bases and the prediction of pharmacokinetic properties of potent molecules by the computational method. Methods: Five protein targets were selected for the study and their structures were taken from RCSB Protein Data Bank in PDB format. Preparation of proteins was done using Discovery Studio 2021 Client. A total of twenty derivatives were drawn using ChemDraw 20.0 and saved in Mol format. Molecular docking was performed using PyRx software. Docking results were visualized by Discovery Studio 2021 Client. The pharmacokinetic properties of the best compounds were determined using the pkCSM tool. Results: All twenty derivatives were docked against the five proteins, namely DNA Ligase (PDB ID: 3PN1), Topoisomerase (PDB ID: 3TTZ), Sterol demethylase (PDB ID: 5FSA), Enoyl-acyl-carrier protein (PDB ID: 1BVR) and Glutamate racemase (PDB ID: 5HJ7). The compound JJB18 has shown the best bindin...
Objective: The present study discusses the molecular docking study of Hentriacontane for its Anti... more Objective: The present study discusses the molecular docking study of Hentriacontane for its Anti-tubercular and Anti-cancer activity. Methods: Two protein targets were selected for the study and their structures were taken from RCSB Protein Data Bank in PDB format. Preparation of proteins was done using Discovery Studio 2021 Client. The structure of Hentriacontane was drawn using ChemDraw 20.0 and saved in Mol format. Molecular docking was performed using PyRx software. 3D and 2D docking interactions were visualized by Discovery Studio 2021 Client. Results: Hentriacontane has docked against the selected proteins, namely Extra-cellular regulated kinase–2 (ERK-2; PDB ID: 3QYW) and Shikimate kinase (PDB ID: 1ZYU). The compound has shown the best binding score against Shikimate kinase (-10.4 kcal/mol), and Extra-cellular regulated kinase–2 (-7.4 kcal/mol) than the standard drugs. Conclusion: Molecular Docking study indicates that Hentriacontane could be an effective inhibitor for the p...
International Journal of Current Pharmaceutical Research
Objective: The present work discusses developing a novel method for estimation of residual solven... more Objective: The present work discusses developing a novel method for estimation of residual solvents in Gliclazide using Gas chromatography and determining its consistency, reliability and reproducibility by performing its validation. Methods: A Gas chromatograph equipped with aflame ionization detector, column DB-624 (60 m x 0.32 mm x 1.8 µm) with Nitrogen as carrier gas was used and the column temperature was 40 °C (hold for 15 min) and increased to 240 °C at 20 °C per min. The solutions were prepared using-Methyl-2-Pyrrolidone (NMP) diluent as per the procedure given in protocol and appropriately injected as per the sequence. The validation parameters checked were System suitability, Specificity, Linearity and Range, Accuracy, Precision, Limit of detection, Limit of quantitation, Ruggedness and Robustness. Results: The data for each validation parameter tested is compiled and documented. It was found that the results obtained for each parameter compiled with their given acceptance...
Cell wall of mycobacterium acts as a primary interface which helps in the regulation of important... more Cell wall of mycobacterium acts as a primary interface which helps in the regulation of important functions and also aids to pathogenicity and virulence of the organism, making it a crucial target for drug discovery. Decaprenylphosphoryl-D-ribose 2 0-epimerase (DprE), is important for the growth and survival of Mycobacterium tuberculosis. DprE1 is a donor of arabinose sugars which helps in the formation of cell wall components-lipoarabinomannan and arabinogalactan through Decaprenyl-phosphoryl D-arabinose (DPA) pathway. In our study, we have chosen Azaindole derivatives as DprE1 inhibitors which possess non-covalent property. TBA7371 (azaindole derivative, non-covalent inhibitor) is currently in first phase of clinical trials as DprE1 inhibitor. Azaindoles have been found to be equally potent against drugsensitive and isoniazid/rifampin-resistant strains. Hence, azaindoles are an attractive class for further optimization as potential DprE1 inhibitors for TB. Structure-based pharmacophore model was generated to investigate the compounds with similar molecular features. Compounds having a good fitness score and pharmacophoric features were compared with the molecules in clinical trial and were proceeded for molecular docking studies to identify the binding affinity of the compounds with target protein DprE1. Energy based calculations using Prime MM-GBSA of Schrodinger was further executed to examine free binding energy of the ligands. The prediction of pharmacokinetic parameters (ADME) plays an important role to identify safe and potent molecules which may further have potential to become drug candidates. Induced-fit docking approach and Molecular Dynamics integrated with Prime MM-GBSA calculations of both hit compounds has further confirmed the binding affinity and stability. All the results obtained from our study were interpreted and compared with DprE1 inhibitor in clinical trials. Study identified ZINC000170252277 as a potential hit compound for further biological evaluation as DprE1 inhibitor.
International Journal of Current Pharmaceutical Research
Objective: The objective of the study is to design novel isoxazole derivatives, predicting their ... more Objective: The objective of the study is to design novel isoxazole derivatives, predicting their interactions with the selected target proteins and determining the ADMET properties of potent molecules using recent computational methods. Methods: With the intent to discover potent novel antibacterial, we have designed a set of compounds containing the isoxazole nucleus by using software tools like Discovery studios, PyRx, PyMOL, SWISSPDB. ADMET studies were carried out by using SWISS ADMET and pkCSM. Molecular docking studies were carried out on the target proteins of both gram-positive and gram negative bacteria in order to assesses binding affinity for the proteins. Results: Designed scaffold was designed by Benzene Derivatives Tethered with 5(4-chloro-3-nitro phenyl-1-yl) isoxazole. All the derivatives were docked against the three proteins, namely DNA Ligase (PDB ID: 3PN1), Topoisomerase (PDB ID: 3TTZ), Sterol demethylase (PDB ID: 5FSA), The compound JJC3F has shown best binding ...
International journal of pharma and bio sciences, 2018
In order to search for new bioactive molecules with significant antimicrobial action, a series of... more In order to search for new bioactive molecules with significant antimicrobial action, a series of 1,2,4-triazole and naphthalene analogs bearing structurally diverse substituents, N-(3-mercapto-5-(naphthalen-1-yl)-4H-1,2,4triazol-4-yl)(aryl)amides 3a-l were synthesized in good yield by a multi-step synthetic procedure. Their antimicrobial activity was screened against various Gram-positive and Gram-negative bacteria and fungi. Compounds 3a, 3f, 3g, 3j, and 3k exerted strong inhibition of the investigated bacterial and fungal strains compared to control antibiotic ampicillin and antifungal griseofulvin. On the basis of statistical analysis, it is observed that the compounds give significant co-relation. All the synthesized compounds have been characterized by IR, 1 H NMR, 13 C NMR, and mass spectral data.
Chitin (β-(1-4)-poly-N-acetyl-d-glucosamine) is considered the second most abundant polysaccharid... more Chitin (β-(1-4)-poly-N-acetyl-d-glucosamine) is considered the second most abundant polysaccharide in nature. Chitin can be degraded into shorter oligosaccharides known as chito-oligosaccharides by either chemical or enzymatic methods. Chitin and its oligosaccharides, being biocompatible and biodegradable, have been reported to have several biomedical applications. The wound healing properties of this polymer have been determined primarily using in vivo studies on various animal models. However little has been studied regarding the mechanism of action of this polymer with regard to wound healing. Wound healing is a highly co-ordinated process involving inflammation, cell proliferation, matrix deposition, tissue remodeling, collagenation and epithelialization. Matrix metalloproteinases (MMPs) are a class enzymes that are structurally similar and contribute to degradation of extracellular matrix. They have a role in both normal and pathological matrix remodelling. Over expression of m...
International journal of pharma and bio sciences, 2010
The present study explores the utility of Quantitative Structure Activity Relationship (QSAR), in... more The present study explores the utility of Quantitative Structure Activity Relationship (QSAR), insilico ADME studies and Quantitative Structure Toxicity Relationship (QSTR) for the established 2! indolinone Lamotrigine Schiff base derivatives. Here, we developed 2D QSAR models for (n=6) 2! indolinone Lamotrigine Schiff base derivatives as cytotoxic agents using the CTC50 values of these compounds obtained by using MTT and SRB bioassay procedure for HEp!2 and DLA cell lines. Multiple regression equations developed using the calculated physicochemical parameters showed that for HEp!2 cell lines, SRB bioassay proc edure gave a better correlation between Van der Waals energy, shape flexibility index, surface area and anti!cancer activity (r 2 >0.95). Similarly for DLA cell lines, MTT bioassay gave better correlation between HOMO (Highest Occupied Molecular Orbital), LogP, molecular refractivity and anti!cancer activity (r 2 >0.99). Also, the in-silico ADME and QSTR evaluation show...
Candida albicans is an opportunistic fungal pathogen that causes candidiasis in human hosts. Cand... more Candida albicans is an opportunistic fungal pathogen that causes candidiasis in human hosts. Candidiasis includes a multitude of fungal infections, including invasive fungal infections, where most patients are immunocompromised; hence, the success of treatment is determined by the efficacy of the antifungal agent. However, with the increase in resistance to the existing drugs, the availability of effective antifungal agents is becoming scarce. Many pyrimidine derivatives exhibit powerful antifungal activity. In this study, In silico antifungal activity was carried out on twenty novel aminopyrimidine derivatives to identify the specificity of the pyrimidine analogues for the antifungal targets using ‘Glide’. Molecular docking studies were conducted on two antifungal targets; Dihydrofolate reductase of C. albicans (PDB ID: 4HOE); N-myristoyl transferase of C. albicans (PDB ID: 1IYK); energy minimization of title compounds was carried out using LigPrep, the protein targets were optimiz...
International journal of pharma and bio sciences, 2011
Due to ever growing need of lead modification and repositioning of various drug molecules; in-sil... more Due to ever growing need of lead modification and repositioning of various drug molecules; in-silico drug design techniques are being considered as the most economical and high through put screening methods. The present study shows not only the importance of Isatins as antimicrobials but also tries to identify and filter useful data pertaining to structural peculiarities which are in turn useful for pharmacological and medicinal predictions. From the present study, it is observed that all the compounds are predicted to have oral bioavailability, considerable chances of human intestinal absorption, and has no BBB penetrations. Available LD50, LC50, LOAEL values suggest that the molecules are safe for the further evaluations. Also from the available data generated by in-silco experimentation, it is predicted that compound 3B have considerable pharmacological profile for further developments. JUDY JAYS Department of Pharmaceutical Chemistry, M.S. Ramaiah College of Pharmacy,
International Journal of Pharmacy and Pharmaceutical Sciences
Benzotriazole derivatives have shown several pharmacological activities, which are antimicrobial ... more Benzotriazole derivatives have shown several pharmacological activities, which are antimicrobial activity, anti-inflammatory, analgesic activity, anticancer. On the basis of our observation the present research work was carried out to synthesize substituted benzotriazole derivatives containing pyrazilidin-3,5dione moieties. The various benzotriazole derivatives were prepared by diazotisation using substituted benzene 1, 2 diamine with glacial acetic acid (1A-1I) the various benzotriazole derivatives were treated with ethyl chloroacetate and anhydrous potassium carbonate to yield its ethyl 1 H benzotriazole-1-yl acetate (2A-2I). The formed acetate is converted into hydrazide (3A-3I) by reacting with various substituted hydrazines. Finally the resulted hydrazides were condensed with diethyl propanedioate to yield some new 1, 2, 3, benzotriazole derivative containing pyrazolidine 3, 5 dione moieties. The entire synthesized compounds were characterized by IR, 1H-NMR, Mass spectroscopy and elemental analysis. Purity of the compounds was checked by using TLC and elemental analysis. The antimicrobial activity of the synthesized compounds was evaluated by cup plate diffusion method. These compounds had a considerable anti-bacterial activity against S. aureus, B. subtilis, E. coli, Proteus vulgaris compared to Ciprofloxacin, Amoxicillin respectively. Similarly compounds had considerable antifungal activity against A. niger, C. albicans compared to Ketoconazole, Clotrimazole respectively.
P r e se n t r e se a r c h w o rk f o c u se s o n in-silico drug design studies of the synthesi... more P r e se n t r e se a r c h w o rk f o c u se s o n in-silico drug design studies of the synthesized (n=9) novel substituted 4-quinolone containing pyrazolidinedione derivatives, screening of non hepatotoxic derivatives and finding out the characteristics of the functional groups responsible for hepatotoxicity in molecules by using in-silico screening of (n=180) hypothetical and novel substituted 4-quinolone containing pyrazolidinedione derivatives. In the present study, zone of inhibition data for (n=9) synthesized compounds obtained against two gram +ve and gram -ve organisms were used to develop multiple regression equations using TSAR soft. with r 2 >0.8, t-probabilities<0.05. In-silico pharmacokinetic studies implied that these derivatives had no CYP450 2D6 inhibitions, low BBB penetration and good oral absorptions. QSTR (Quantitative Structure Toxicity Relationship) studies by using TOPKAT (v6.1) in various computational animal models showed considerable safety. This was...
There has been a biggest problem of bacterial resistance ever since the development of anti-bacte... more There has been a biggest problem of bacterial resistance ever since the development of anti-bacterial agents. The present research work focuses on the microwave assisted solvent less synthesis combined with conventional stirring and refluxation methods to form some novel substituted 4-quinolone pyrazolidinedione derivatives. The characterisation of n=9 derivatives was carried out using I.R, 1 H NMR and mass spectral analysis. The percentage yield of final compounds was found to be 22.15 to 69.68. Purity of the compounds was checked by using TLC and elemental analysis. These compounds showed a considerable anti-bacterial activity against S. aureus, B. subtilis, Klebesiella pneumoniae and Proteus vulgaris and anti-inflammatory activity using Invitro testing methods compared to Ciprofloxacin, Amoxicillin and Ibuprofen respectively.
International Journal of Pharma and Bio Sciences, 2018
A new organoborate ligand, hydro(benzoyl)(phthalyl)borate has been synthesized as its potassium s... more A new organoborate ligand, hydro(benzoyl)(phthalyl)borate has been synthesized as its potassium salt (KL) and treatment of KL with one equivalent of MCl 2 •6H 2 O gave complexes ML(H 2 O) x •Cl [x＝2, M＝Co(II), Ni(II); x＝1, M＝Cu(II)]. All compounds were characterized by elemental analysis, FTIR, 1 H NMR, ESI MS, UV-Vis techniques, conductivity and magnetic data measurements. Spectroscopic results suggest a square planar geometry in the Cu(II) complex, while the Co(II) and Ni(II) complexes possess an octahedral geometry. Antibacterial activities (in vitro) of the ligand and its metal complexes were studied against two Gram positive (B. subtillis and B. magterium) and two Gram negative bacteria (E. Coli and S. boydi) at a single concentration (75 µg/mL) by using the Disc diffusion method. Antifungal activities (in vitro) were also checked for the compounds by using the same method against Candida albicans 10261, Penicillium sp. and Asperjillius niger., at a single concentration (50 µg/mL). The results showed that all the metal complexes, specially the nickel(II) complex, have higher antibacterial and antifungal activities than the corresponding potassium salt.
International journal of pharmacy and pharmaceutical sciences/International Journal of Pharmacy and Pharmaceutical Sciences, Apr 1, 2024
Objective: Universal use of antibacterial agents and swift development of resistance by the micro... more Objective: Universal use of antibacterial agents and swift development of resistance by the microorganisms pose a major threat to public health. Hence, there is a pressing need to develop novel antimicrobials. Isoxazole derivatives exhibiting versatile biological activities have been widely used as important scaffolds in the field of drug designing. Methods: Twenty isoxazole derivatives were virtually screened by means of the molecular docking approach in order to identify potential antimicrobials against the most common disease-causing bacteria, S. aureus. In silico studies were done to detect the selectivity of the novel isoxazole derivatives for the selected bacterial protein targets using 'Glide'. In silico docking was carried out on few essential enzymes of S. aureus; Dihydrofolate reductase (DHFR), DNA gyrase, Dihydropteroate Synthetase (DHPS), Pyuvate kinase (PK). The compounds were subjected to energy minimization, followed by optimization and minimization of protein and generation of 3D grid at its active site. The ligands were subjected to molecular docking the Standard Precision and Extra Precision modes. Results: Docking of the compounds with Pyruvate Kinase and dihydrofolate reductase are quite encouraging.2C (4-hydroxy) and 2D (4-hydroxy) analogues gavea G Score of-8.33 and-8.64 with DHFR and Pyruvate Kinase respectively. However, the dock scores for the other target proteins indicate that the scaffolds have not bound with those bacterial targets. Moreover, ADME studies indicate that the derivatives do not show any violations in the rules for the requirements of orally active drugs. Conclusion: Study suggests that the derivatives 2C (4-hydroxy) and 2D(2-hydroxy) specifically bind to the active site of PK and DHFR. In silico ADME studies predicted the compounds to be "drug-like." Hence the hydroxy derivatives may be considered as leads for further structural modifications to arrive at potential anti-bacterial agents.
International Journal of Current Pharmaceutical Research, Jul 15, 2022
Objective: The present work discusses developing a novel method for estimation of residual solven... more Objective: The present work discusses developing a novel method for estimation of residual solvents in Gliclazide using Gas chromatography and determining its consistency, reliability and reproducibility by performing its validation. Methods: A Gas chromatograph equipped with aflame ionization detector, column DB-624 (60 m x 0.32 mm x 1.8 µm) with Nitrogen as carrier gas was used and the column temperature was 40 °C (hold for 15 min) and increased to 240 °C at 20 °C per min. The solutions were prepared using-Methyl-2-Pyrrolidone (NMP) diluent as per the procedure given in protocol and appropriately injected as per the sequence. The validation parameters checked were System suitability, Specificity, Linearity and Range, Accuracy, Precision, Limit of detection, Limit of quantitation, Ruggedness and Robustness. Results: The data for each validation parameter tested is compiled and documented. It was found that the results obtained for each parameter compiled with their given acceptance criteria. Hence, the developed method was considered reproducible, reliable and consistent. Conclusion: The method of analysis complies with all the parameters tested and it was found to be reliable, consistent and reproducible.
International Journal of Pharmacy and Pharmaceutical Sciences, Aug 1, 2022
Objective: The present study discusses molecular docking of some novel coumarin-benzothiazole Sch... more Objective: The present study discusses molecular docking of some novel coumarin-benzothiazole Schiff bases and the prediction of pharmacokinetic properties of potent molecules by the computational method. Methods: Five protein targets were selected for the study and their structures were taken from RCSB Protein Data Bank in PDB format. Preparation of proteins was done using Discovery Studio 2021 Client. A total of twenty derivatives were drawn using ChemDraw 20.0 and saved in Mol format. Molecular docking was performed using PyRx software. Docking results were visualized by Discovery Studio 2021 Client. The pharmacokinetic properties of the best compounds were determined using the pkCSM tool. Results: All twenty derivatives were docked against the five proteins, namely DNA Ligase (PDB ID: 3PN1), Topoisomerase (PDB ID: 3TTZ), Sterol demethylase (PDB ID: 5FSA), Enoyl-acyl-carrier protein (PDB ID: 1BVR) and Glutamate racemase (PDB ID: 5HJ7). The compound JJB18 has shown the best binding score against DNA ligase (-10.7 kcal/mol), Glutamate racemase (-8.4 kcal/mol), and Enoyl-acyl-carrier protein (-10.8 kcal/mol). Further, compound JJB19 has shown the best score for fungal sterol demethylase (-10.6 kcal/mol) and compound JJB20 towards topoisomerase (-9.4 kcal/mol) than the standard drugs. The physicochemical properties of potent derivatives were also reported. Conclusion: Molecular Docking study indicates that coumarin-benzothiazole Schiff bases may be effective inhibitors for the different microbial proteins. Additionally, in silico ADMET studies predicts drug-like features. Hence, these compounds may be considered lead molecules and further investigation of their analogues may help in the development of novel drugs for the treatment of microbial diseases.
International Journal of Pharmacy and Pharmaceutical Sciences
Objective: The present study discusses molecular docking of some novel coumarin–benzothiazole Sch... more Objective: The present study discusses molecular docking of some novel coumarin–benzothiazole Schiff bases and the prediction of pharmacokinetic properties of potent molecules by the computational method. Methods: Five protein targets were selected for the study and their structures were taken from RCSB Protein Data Bank in PDB format. Preparation of proteins was done using Discovery Studio 2021 Client. A total of twenty derivatives were drawn using ChemDraw 20.0 and saved in Mol format. Molecular docking was performed using PyRx software. Docking results were visualized by Discovery Studio 2021 Client. The pharmacokinetic properties of the best compounds were determined using the pkCSM tool. Results: All twenty derivatives were docked against the five proteins, namely DNA Ligase (PDB ID: 3PN1), Topoisomerase (PDB ID: 3TTZ), Sterol demethylase (PDB ID: 5FSA), Enoyl-acyl-carrier protein (PDB ID: 1BVR) and Glutamate racemase (PDB ID: 5HJ7). The compound JJB18 has shown the best bindin...
Objective: The present study discusses the molecular docking study of Hentriacontane for its Anti... more Objective: The present study discusses the molecular docking study of Hentriacontane for its Anti-tubercular and Anti-cancer activity. Methods: Two protein targets were selected for the study and their structures were taken from RCSB Protein Data Bank in PDB format. Preparation of proteins was done using Discovery Studio 2021 Client. The structure of Hentriacontane was drawn using ChemDraw 20.0 and saved in Mol format. Molecular docking was performed using PyRx software. 3D and 2D docking interactions were visualized by Discovery Studio 2021 Client. Results: Hentriacontane has docked against the selected proteins, namely Extra-cellular regulated kinase–2 (ERK-2; PDB ID: 3QYW) and Shikimate kinase (PDB ID: 1ZYU). The compound has shown the best binding score against Shikimate kinase (-10.4 kcal/mol), and Extra-cellular regulated kinase–2 (-7.4 kcal/mol) than the standard drugs. Conclusion: Molecular Docking study indicates that Hentriacontane could be an effective inhibitor for the p...
International Journal of Current Pharmaceutical Research
Objective: The present work discusses developing a novel method for estimation of residual solven... more Objective: The present work discusses developing a novel method for estimation of residual solvents in Gliclazide using Gas chromatography and determining its consistency, reliability and reproducibility by performing its validation. Methods: A Gas chromatograph equipped with aflame ionization detector, column DB-624 (60 m x 0.32 mm x 1.8 µm) with Nitrogen as carrier gas was used and the column temperature was 40 °C (hold for 15 min) and increased to 240 °C at 20 °C per min. The solutions were prepared using-Methyl-2-Pyrrolidone (NMP) diluent as per the procedure given in protocol and appropriately injected as per the sequence. The validation parameters checked were System suitability, Specificity, Linearity and Range, Accuracy, Precision, Limit of detection, Limit of quantitation, Ruggedness and Robustness. Results: The data for each validation parameter tested is compiled and documented. It was found that the results obtained for each parameter compiled with their given acceptance...
Cell wall of mycobacterium acts as a primary interface which helps in the regulation of important... more Cell wall of mycobacterium acts as a primary interface which helps in the regulation of important functions and also aids to pathogenicity and virulence of the organism, making it a crucial target for drug discovery. Decaprenylphosphoryl-D-ribose 2 0-epimerase (DprE), is important for the growth and survival of Mycobacterium tuberculosis. DprE1 is a donor of arabinose sugars which helps in the formation of cell wall components-lipoarabinomannan and arabinogalactan through Decaprenyl-phosphoryl D-arabinose (DPA) pathway. In our study, we have chosen Azaindole derivatives as DprE1 inhibitors which possess non-covalent property. TBA7371 (azaindole derivative, non-covalent inhibitor) is currently in first phase of clinical trials as DprE1 inhibitor. Azaindoles have been found to be equally potent against drugsensitive and isoniazid/rifampin-resistant strains. Hence, azaindoles are an attractive class for further optimization as potential DprE1 inhibitors for TB. Structure-based pharmacophore model was generated to investigate the compounds with similar molecular features. Compounds having a good fitness score and pharmacophoric features were compared with the molecules in clinical trial and were proceeded for molecular docking studies to identify the binding affinity of the compounds with target protein DprE1. Energy based calculations using Prime MM-GBSA of Schrodinger was further executed to examine free binding energy of the ligands. The prediction of pharmacokinetic parameters (ADME) plays an important role to identify safe and potent molecules which may further have potential to become drug candidates. Induced-fit docking approach and Molecular Dynamics integrated with Prime MM-GBSA calculations of both hit compounds has further confirmed the binding affinity and stability. All the results obtained from our study were interpreted and compared with DprE1 inhibitor in clinical trials. Study identified ZINC000170252277 as a potential hit compound for further biological evaluation as DprE1 inhibitor.
International Journal of Current Pharmaceutical Research
Objective: The objective of the study is to design novel isoxazole derivatives, predicting their ... more Objective: The objective of the study is to design novel isoxazole derivatives, predicting their interactions with the selected target proteins and determining the ADMET properties of potent molecules using recent computational methods. Methods: With the intent to discover potent novel antibacterial, we have designed a set of compounds containing the isoxazole nucleus by using software tools like Discovery studios, PyRx, PyMOL, SWISSPDB. ADMET studies were carried out by using SWISS ADMET and pkCSM. Molecular docking studies were carried out on the target proteins of both gram-positive and gram negative bacteria in order to assesses binding affinity for the proteins. Results: Designed scaffold was designed by Benzene Derivatives Tethered with 5(4-chloro-3-nitro phenyl-1-yl) isoxazole. All the derivatives were docked against the three proteins, namely DNA Ligase (PDB ID: 3PN1), Topoisomerase (PDB ID: 3TTZ), Sterol demethylase (PDB ID: 5FSA), The compound JJC3F has shown best binding ...
International journal of pharma and bio sciences, 2018
In order to search for new bioactive molecules with significant antimicrobial action, a series of... more In order to search for new bioactive molecules with significant antimicrobial action, a series of 1,2,4-triazole and naphthalene analogs bearing structurally diverse substituents, N-(3-mercapto-5-(naphthalen-1-yl)-4H-1,2,4triazol-4-yl)(aryl)amides 3a-l were synthesized in good yield by a multi-step synthetic procedure. Their antimicrobial activity was screened against various Gram-positive and Gram-negative bacteria and fungi. Compounds 3a, 3f, 3g, 3j, and 3k exerted strong inhibition of the investigated bacterial and fungal strains compared to control antibiotic ampicillin and antifungal griseofulvin. On the basis of statistical analysis, it is observed that the compounds give significant co-relation. All the synthesized compounds have been characterized by IR, 1 H NMR, 13 C NMR, and mass spectral data.
Chitin (β-(1-4)-poly-N-acetyl-d-glucosamine) is considered the second most abundant polysaccharid... more Chitin (β-(1-4)-poly-N-acetyl-d-glucosamine) is considered the second most abundant polysaccharide in nature. Chitin can be degraded into shorter oligosaccharides known as chito-oligosaccharides by either chemical or enzymatic methods. Chitin and its oligosaccharides, being biocompatible and biodegradable, have been reported to have several biomedical applications. The wound healing properties of this polymer have been determined primarily using in vivo studies on various animal models. However little has been studied regarding the mechanism of action of this polymer with regard to wound healing. Wound healing is a highly co-ordinated process involving inflammation, cell proliferation, matrix deposition, tissue remodeling, collagenation and epithelialization. Matrix metalloproteinases (MMPs) are a class enzymes that are structurally similar and contribute to degradation of extracellular matrix. They have a role in both normal and pathological matrix remodelling. Over expression of m...
International journal of pharma and bio sciences, 2010
The present study explores the utility of Quantitative Structure Activity Relationship (QSAR), in... more The present study explores the utility of Quantitative Structure Activity Relationship (QSAR), insilico ADME studies and Quantitative Structure Toxicity Relationship (QSTR) for the established 2! indolinone Lamotrigine Schiff base derivatives. Here, we developed 2D QSAR models for (n=6) 2! indolinone Lamotrigine Schiff base derivatives as cytotoxic agents using the CTC50 values of these compounds obtained by using MTT and SRB bioassay procedure for HEp!2 and DLA cell lines. Multiple regression equations developed using the calculated physicochemical parameters showed that for HEp!2 cell lines, SRB bioassay proc edure gave a better correlation between Van der Waals energy, shape flexibility index, surface area and anti!cancer activity (r 2 >0.95). Similarly for DLA cell lines, MTT bioassay gave better correlation between HOMO (Highest Occupied Molecular Orbital), LogP, molecular refractivity and anti!cancer activity (r 2 >0.99). Also, the in-silico ADME and QSTR evaluation show...
Candida albicans is an opportunistic fungal pathogen that causes candidiasis in human hosts. Cand... more Candida albicans is an opportunistic fungal pathogen that causes candidiasis in human hosts. Candidiasis includes a multitude of fungal infections, including invasive fungal infections, where most patients are immunocompromised; hence, the success of treatment is determined by the efficacy of the antifungal agent. However, with the increase in resistance to the existing drugs, the availability of effective antifungal agents is becoming scarce. Many pyrimidine derivatives exhibit powerful antifungal activity. In this study, In silico antifungal activity was carried out on twenty novel aminopyrimidine derivatives to identify the specificity of the pyrimidine analogues for the antifungal targets using ‘Glide’. Molecular docking studies were conducted on two antifungal targets; Dihydrofolate reductase of C. albicans (PDB ID: 4HOE); N-myristoyl transferase of C. albicans (PDB ID: 1IYK); energy minimization of title compounds was carried out using LigPrep, the protein targets were optimiz...
International journal of pharma and bio sciences, 2011
Due to ever growing need of lead modification and repositioning of various drug molecules; in-sil... more Due to ever growing need of lead modification and repositioning of various drug molecules; in-silico drug design techniques are being considered as the most economical and high through put screening methods. The present study shows not only the importance of Isatins as antimicrobials but also tries to identify and filter useful data pertaining to structural peculiarities which are in turn useful for pharmacological and medicinal predictions. From the present study, it is observed that all the compounds are predicted to have oral bioavailability, considerable chances of human intestinal absorption, and has no BBB penetrations. Available LD50, LC50, LOAEL values suggest that the molecules are safe for the further evaluations. Also from the available data generated by in-silco experimentation, it is predicted that compound 3B have considerable pharmacological profile for further developments. JUDY JAYS Department of Pharmaceutical Chemistry, M.S. Ramaiah College of Pharmacy,
International Journal of Pharmacy and Pharmaceutical Sciences
Benzotriazole derivatives have shown several pharmacological activities, which are antimicrobial ... more Benzotriazole derivatives have shown several pharmacological activities, which are antimicrobial activity, anti-inflammatory, analgesic activity, anticancer. On the basis of our observation the present research work was carried out to synthesize substituted benzotriazole derivatives containing pyrazilidin-3,5dione moieties. The various benzotriazole derivatives were prepared by diazotisation using substituted benzene 1, 2 diamine with glacial acetic acid (1A-1I) the various benzotriazole derivatives were treated with ethyl chloroacetate and anhydrous potassium carbonate to yield its ethyl 1 H benzotriazole-1-yl acetate (2A-2I). The formed acetate is converted into hydrazide (3A-3I) by reacting with various substituted hydrazines. Finally the resulted hydrazides were condensed with diethyl propanedioate to yield some new 1, 2, 3, benzotriazole derivative containing pyrazolidine 3, 5 dione moieties. The entire synthesized compounds were characterized by IR, 1H-NMR, Mass spectroscopy and elemental analysis. Purity of the compounds was checked by using TLC and elemental analysis. The antimicrobial activity of the synthesized compounds was evaluated by cup plate diffusion method. These compounds had a considerable anti-bacterial activity against S. aureus, B. subtilis, E. coli, Proteus vulgaris compared to Ciprofloxacin, Amoxicillin respectively. Similarly compounds had considerable antifungal activity against A. niger, C. albicans compared to Ketoconazole, Clotrimazole respectively.
P r e se n t r e se a r c h w o rk f o c u se s o n in-silico drug design studies of the synthesi... more P r e se n t r e se a r c h w o rk f o c u se s o n in-silico drug design studies of the synthesized (n=9) novel substituted 4-quinolone containing pyrazolidinedione derivatives, screening of non hepatotoxic derivatives and finding out the characteristics of the functional groups responsible for hepatotoxicity in molecules by using in-silico screening of (n=180) hypothetical and novel substituted 4-quinolone containing pyrazolidinedione derivatives. In the present study, zone of inhibition data for (n=9) synthesized compounds obtained against two gram +ve and gram -ve organisms were used to develop multiple regression equations using TSAR soft. with r 2 >0.8, t-probabilities<0.05. In-silico pharmacokinetic studies implied that these derivatives had no CYP450 2D6 inhibitions, low BBB penetration and good oral absorptions. QSTR (Quantitative Structure Toxicity Relationship) studies by using TOPKAT (v6.1) in various computational animal models showed considerable safety. This was...
There has been a biggest problem of bacterial resistance ever since the development of anti-bacte... more There has been a biggest problem of bacterial resistance ever since the development of anti-bacterial agents. The present research work focuses on the microwave assisted solvent less synthesis combined with conventional stirring and refluxation methods to form some novel substituted 4-quinolone pyrazolidinedione derivatives. The characterisation of n=9 derivatives was carried out using I.R, 1 H NMR and mass spectral analysis. The percentage yield of final compounds was found to be 22.15 to 69.68. Purity of the compounds was checked by using TLC and elemental analysis. These compounds showed a considerable anti-bacterial activity against S. aureus, B. subtilis, Klebesiella pneumoniae and Proteus vulgaris and anti-inflammatory activity using Invitro testing methods compared to Ciprofloxacin, Amoxicillin and Ibuprofen respectively.
International Journal of Pharma and Bio Sciences, 2018
A new organoborate ligand, hydro(benzoyl)(phthalyl)borate has been synthesized as its potassium s... more A new organoborate ligand, hydro(benzoyl)(phthalyl)borate has been synthesized as its potassium salt (KL) and treatment of KL with one equivalent of MCl 2 •6H 2 O gave complexes ML(H 2 O) x •Cl [x＝2, M＝Co(II), Ni(II); x＝1, M＝Cu(II)]. All compounds were characterized by elemental analysis, FTIR, 1 H NMR, ESI MS, UV-Vis techniques, conductivity and magnetic data measurements. Spectroscopic results suggest a square planar geometry in the Cu(II) complex, while the Co(II) and Ni(II) complexes possess an octahedral geometry. Antibacterial activities (in vitro) of the ligand and its metal complexes were studied against two Gram positive (B. subtillis and B. magterium) and two Gram negative bacteria (E. Coli and S. boydi) at a single concentration (75 µg/mL) by using the Disc diffusion method. Antifungal activities (in vitro) were also checked for the compounds by using the same method against Candida albicans 10261, Penicillium sp. and Asperjillius niger., at a single concentration (50 µg/mL). The results showed that all the metal complexes, specially the nickel(II) complex, have higher antibacterial and antifungal activities than the corresponding potassium salt.
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Papers by Dr Judy Jays