Mohane Coumar - Academia.edu (original) (raw)

Papers by Mohane Coumar

Elsevier eBooks, 2021

Abstract The clinical trial is the final stage of a long and careful research and development pro... more Abstract The clinical trial is the final stage of a long and careful research and development process (drug/vaccine/medical device). Clinical trials should follow strict step by step process and scientific standards to protect and prevent patients from diseases. The primary purpose of the clinical trial is to make sure that the product is safe, effective and bringing value to the mankind.

Expert Opinion on Therapeutic Patents, May 24, 2016

ABSTRACT Evaluation of the patent application WO2015036792 claiming therapeutic polymeric nanopar... more ABSTRACT Evaluation of the patent application WO2015036792 claiming therapeutic polymeric nanoparticles loaded with AZD1152-hqpa (aurora kinase inhibitor), and methods of making and using same for the treatment of cancer, is described. The claimed polymeric nano-formulations containing hydrophobic acid significantly improved the pharmacokinetic profiles (slow/sustained drug release profile) of the drug AZD1152-hqpa, as compared to the control agent (AZD1152). Drug efficacy and tolerability were also improved, and toxicity decreased in in vivo animal experiments, resulting in a better therapeutic index for the nano-formulation. Hence, the nano-formulated AZD1152-hqpa could be tested in the clinic at a dose level similar to, or higher than, that used for AZD1152, with lower incidence of toxicity.

Journal of Biomolecular Structure & Dynamics, Nov 17, 2018

Mono-and di-methylation of the H3K9 residue in the histone tail by G9a lysine methyltransferase i... more Mono-and di-methylation of the H3K9 residue in the histone tail by G9a lysine methyltransferase is associated with transcriptional suppression of genes. Here, we use molecular dynamics simulation and free energy calculations of five different modified/mutated G9a substrate peptides to elucidate the rationale behind the substrate binding to G9a. We also investigated the binding energy contribution based architecture of the active site of G9a to understand substrate and inhibitor binding. Wild type peptide (H3K9) shows better binding affinity than mono-and di-methylated lysine (K9) and other modified peptides (K9A and R8A). Arg8 of the substrate peptide is crucial for determining the degree of conformational freedom/stability of the wild type substrate peptide, as well as binding to G9a. Our results also suggest that the G9a active site is segregated into energy rich and low regions, and the energy rich region alone is used by the inhibitors for binding. These insights into the active site architecture should be taken into consideration in virtual screening experiments designed to discover novel inhibitors for G9a. In particular, compounds that could interact with the six residues of G9a

ABSTRACT Export Date: 4 May 2013, Source: Scopus, CODEN: INDRB, Language of Original Document: En... more ABSTRACT Export Date: 4 May 2013, Source: Scopus, CODEN: INDRB, Language of Original Document: English, Correspondence Address: Bodhankar, S.L.; Department of Pharmacology, Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Erandwane, Pune-411 038, India; email: sbodh@yahoo.com

The challenge of next-generation nanoparticles (NPs) includes limited cellular uptake and loss by... more The challenge of next-generation nanoparticles (NPs) includes limited cellular uptake and loss by phagocytosis. General surface modification of NPs potentially enhances evasion from phagocytosis. However, active targeting and enhanced cellular uptake of nanoparticles are possible by surface functionalisation with molecules that have selective affinity for cancer cells. ROR1 is a cell surface receptor that is over-expressed in cancer cells. Hence, its conjugate antibody could be a potential surface functionalisation molecule. In the current study, anti-ROR1 antibody has been covalently attached to nanoparticles' surface, thereby imparting its active targeting potential. Physicochemical and in vitro characterisations of the antibody-conjugated nanoparticles were performed. Surface functionalisation of nanoparticles was confirmed by scanning electron microscopy, isothermal calorimetry, and elemental analysis. Additionally, biomarkers of metastasis and epithelial-mesenchymal transition (EMT) were studied. Anti-ROR1 mAb tagged nanoparticles further confirmed therapeutic efficacy against colon cancer cells, SW480, thus, opening scope for further in vivo studies.

Elsevier eBooks, 2021

Abstract Drug discovery is an arduous, time consuming and expensive process requiring several yea... more Abstract Drug discovery is an arduous, time consuming and expensive process requiring several years and a huge amount of funding. Identifying a potential drug target and suitable lead molecule for drug development are critical steps in the drug discovery process. Among the various methods available for the identification of new lead molecules, structural bioinformatics has a special place. Structural bioinformatics plays a vital role in target validation, active site identification, lead optimization, drug-likeness prediction and stability analysis. The structural bioinformatics helps in identifying and designing novel leads against a selected drug target that could be tested experimentally to check the impact on the biological system.

Medical Oncology, Jul 20, 2017

DNA methyltransferases make use of alternative splicing mechanism to generate various splice vari... more DNA methyltransferases make use of alternative splicing mechanism to generate various splice variants, but their role(s) in modulating DNA methylation patterns in the cells is unclear. Notably, DNMT3B alone contains nearly 40 different splice variants. In this study, we have identified a novel splice variant of DNMT3B, which lacks exon 7 and 10 from leukemic cell lines which we termed as DNMT3B9. The exon 7 codes for the major part of PWWP domain, and exon 10 inclusion serves as a pluripotent marker. By quantitative RT-PCR using exon-exon junction-specific primers, we showed higher level of DNMT3B9 transcripts in several leukemic cell lines. However, DNMT3B9 expression was less in other tested cancer cell lines indicating that DNMT3B9 might serve as a leukemic-specific biomarker. Surprisingly, endogenous protein for DNMT3B9 was not detected in leukemic cells suggesting the unidentified RNA-related function(s) for DNMT3B9. In addition, we showed that DNMT3B9 protein lacks PWWP domain is less stable compared to other DNMT3B variants which contain PWWP domain through computational predictions and by cycloheximide half-life experiment. Taken together, we demonstrated the existence of novel leukemic-specific splice variant of DNMT3B and provide the evidence for the role of PWWP domain in the stability of DNMT3B. The findings reported here have relevance in epigenetic therapy, which is aimed to target the DNMT3B in cancer cells.

Bioorganic Chemistry, May 1, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

European Journal of Pharmaceutical Sciences, Aug 1, 2003

Potential of piperine, an active alkaloid of black and long peppers, to increase the bioavailabil... more Potential of piperine, an active alkaloid of black and long peppers, to increase the bioavailability of drugs in humans is of great clinical significance owing to its omnipresence in food. In an attempt to further study the reported differences in its metabolism in rats and humans, a new major urinary metabolite was detected in rat urine and plasma using HPLC. The metabolite was partially purified using reverse phase column chromatography on Sephadex((R))-LH 20 and characterized as 5-(3, 4-methylenedioxy phenyl)-2E,4E-pentadienoic acid-N-(3-yl propionic acid)-amide with the help of LC/NMR/positive ESI-MS studies. Complete mass fragmentation pattern could be assigned with MS/MS studies. The metabolite has a unique structure compared to the previously reported metabolites in that it retains methylenedioxy ring and conjugated double bonds while the piperidine ring is modified to form propionic acid group. Mechanism of formation of the metabolite by oxidation and cleavage of piperidine ring is proposed. Kidney appears to be the major excretion route for piperine metabolites in rats as no metabolite could be detected in feces.

Current Computer-Aided Drug Design, 2021

Background: A multi-objective genetic algorithm for De novo drug design (MoGADdrug) has been prop... more Background: A multi-objective genetic algorithm for De novo drug design (MoGADdrug) has been proposed in this paper for the design of novel drug-like molecules similar to some reference molecules. The algorithm developed accepts a set of fragments extracted from approved drugs and available in fragment libraries and combines them according to specified rules to discover new drugs through the in-silico method. Method: For this process, a genetic algorithm has been used, which encodes the fragments as genes of variable length chromosomes and applies various genetic operators throughout the generations. A weighted sum approach is used to simultaneously optimize the structural similarity of the new drug to a reference molecule as well as its drug-likeness property. Results: Five reference molecules namely Lidocaine, Furano-pyrimidine derivative, Imatinib, Atorvastatin and Glipizide have been chosen for the performance evaluation of the algorithm. Conclusion: Also, the newly designed mol...

International Journal of Intelligent Systems and Applications, 2019

Swarm intelligence algorithms are designed to mimic the natural behaviors of living organisms. Th... more Swarm intelligence algorithms are designed to mimic the natural behaviors of living organisms. The birds, animals and insects exhibit extraordinary problem solving behaviors and intelligence when living in colonies or groups. These unique behaviors form the basis for the design of the Metaheuristic which are helpful in solving several real-life combinatorial optimization problems. Monkey algorithm is developed based on the unique behaviors of monkeys such as mountain and tree climbing, jumping, watching and somersaulting. This paper reports for the first time the design and development of Multi-objective Monkey Algorithm (MoMA) and its use for the design of molecules with optimal drug-like properties. Finally, the performance of the proposed MoMA for Drug design (MoMADrug) is compared with the previously disclosed Multi-objective Genetic algorithm (MoGADdrug) for the design of drug-like molecules.

Medical oncology (Northwood, London, England), 2017

DNA methyltransferases make use of alternative splicing mechanism to generate various splice vari... more DNA methyltransferases make use of alternative splicing mechanism to generate various splice variants, but their role(s) in modulating DNA methylation patterns in the cells is unclear. Notably, DNMT3B alone contains nearly 40 different splice variants. In this study, we have identified a novel splice variant of DNMT3B, which lacks exon 7 and 10 from leukemic cell lines which we termed as DNMT3B9. The exon 7 codes for the major part of PWWP domain, and exon 10 inclusion serves as a pluripotent marker. By quantitative RT-PCR using exon-exon junction-specific primers, we showed higher level of DNMT3B9 transcripts in several leukemic cell lines. However, DNMT3B9 expression was less in other tested cancer cell lines indicating that DNMT3B9 might serve as a leukemic-specific biomarker. Surprisingly, endogenous protein for DNMT3B9 was not detected in leukemic cells suggesting the unidentified RNA-related function(s) for DNMT3B9. In addition, we showed that DNMT3B9 protein lacks PWWP domain...

European Journal of Pharmaceutical Sciences, 2003

Potential of piperine, an active alkaloid of black and long peppers, to increase the bioavailabil... more Potential of piperine, an active alkaloid of black and long peppers, to increase the bioavailability of drugs in humans is of great clinical significance owing to its omnipresence in food. In an attempt to further study the reported differences in its metabolism in rats and humans, a new major urinary metabolite was detected in rat urine and plasma using HPLC. The metabolite was partially purified using reverse phase column chromatography on Sephadex((R))-LH 20 and characterized as 5-(3, 4-methylenedioxy phenyl)-2E,4E-pentadienoic acid-N-(3-yl propionic acid)-amide with the help of LC/NMR/positive ESI-MS studies. Complete mass fragmentation pattern could be assigned with MS/MS studies. The metabolite has a unique structure compared to the previously reported metabolites in that it retains methylenedioxy ring and conjugated double bonds while the piperidine ring is modified to form propionic acid group. Mechanism of formation of the metabolite by oxidation and cleavage of piperidine ring is proposed. Kidney appears to be the major excretion route for piperine metabolites in rats as no metabolite could be detected in feces.

ChemInform, 2004

Isoindole derivatives Isoindole derivatives R 0140 Synthesis of 4-(1-Oxo-isoindoline)-, 4-(5,6-Di... more Isoindole derivatives Isoindole derivatives R 0140 Synthesis of 4-(1-Oxo-isoindoline)-, 4-(5,6-Dimethoxy-1-oxo-isoindoline) and 4-Acetamido-Substituted Phenoxy-3-amino-propane Derivatives and Their β 1-, β 2-Adrenergic Receptor Binding Studies.-The β-adrenoceptor binding affinity and selectivity of the synthesized compounds (V) are tested. All the tested compounds (V) exhibit better cardioselectivity than the standard cardioselective β-blocker atenolol.

Acta Crystallographica Section E Structure Reports Online, 2002

Elsevier eBooks, 2021

Abstract The clinical trial is the final stage of a long and careful research and development pro... more Abstract The clinical trial is the final stage of a long and careful research and development process (drug/vaccine/medical device). Clinical trials should follow strict step by step process and scientific standards to protect and prevent patients from diseases. The primary purpose of the clinical trial is to make sure that the product is safe, effective and bringing value to the mankind.

Expert Opinion on Therapeutic Patents, May 24, 2016

ABSTRACT Evaluation of the patent application WO2015036792 claiming therapeutic polymeric nanopar... more ABSTRACT Evaluation of the patent application WO2015036792 claiming therapeutic polymeric nanoparticles loaded with AZD1152-hqpa (aurora kinase inhibitor), and methods of making and using same for the treatment of cancer, is described. The claimed polymeric nano-formulations containing hydrophobic acid significantly improved the pharmacokinetic profiles (slow/sustained drug release profile) of the drug AZD1152-hqpa, as compared to the control agent (AZD1152). Drug efficacy and tolerability were also improved, and toxicity decreased in in vivo animal experiments, resulting in a better therapeutic index for the nano-formulation. Hence, the nano-formulated AZD1152-hqpa could be tested in the clinic at a dose level similar to, or higher than, that used for AZD1152, with lower incidence of toxicity.

Journal of Biomolecular Structure & Dynamics, Nov 17, 2018

Mono-and di-methylation of the H3K9 residue in the histone tail by G9a lysine methyltransferase i... more Mono-and di-methylation of the H3K9 residue in the histone tail by G9a lysine methyltransferase is associated with transcriptional suppression of genes. Here, we use molecular dynamics simulation and free energy calculations of five different modified/mutated G9a substrate peptides to elucidate the rationale behind the substrate binding to G9a. We also investigated the binding energy contribution based architecture of the active site of G9a to understand substrate and inhibitor binding. Wild type peptide (H3K9) shows better binding affinity than mono-and di-methylated lysine (K9) and other modified peptides (K9A and R8A). Arg8 of the substrate peptide is crucial for determining the degree of conformational freedom/stability of the wild type substrate peptide, as well as binding to G9a. Our results also suggest that the G9a active site is segregated into energy rich and low regions, and the energy rich region alone is used by the inhibitors for binding. These insights into the active site architecture should be taken into consideration in virtual screening experiments designed to discover novel inhibitors for G9a. In particular, compounds that could interact with the six residues of G9a

ABSTRACT Export Date: 4 May 2013, Source: Scopus, CODEN: INDRB, Language of Original Document: En... more ABSTRACT Export Date: 4 May 2013, Source: Scopus, CODEN: INDRB, Language of Original Document: English, Correspondence Address: Bodhankar, S.L.; Department of Pharmacology, Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Erandwane, Pune-411 038, India; email: sbodh@yahoo.com

The challenge of next-generation nanoparticles (NPs) includes limited cellular uptake and loss by... more The challenge of next-generation nanoparticles (NPs) includes limited cellular uptake and loss by phagocytosis. General surface modification of NPs potentially enhances evasion from phagocytosis. However, active targeting and enhanced cellular uptake of nanoparticles are possible by surface functionalisation with molecules that have selective affinity for cancer cells. ROR1 is a cell surface receptor that is over-expressed in cancer cells. Hence, its conjugate antibody could be a potential surface functionalisation molecule. In the current study, anti-ROR1 antibody has been covalently attached to nanoparticles' surface, thereby imparting its active targeting potential. Physicochemical and in vitro characterisations of the antibody-conjugated nanoparticles were performed. Surface functionalisation of nanoparticles was confirmed by scanning electron microscopy, isothermal calorimetry, and elemental analysis. Additionally, biomarkers of metastasis and epithelial-mesenchymal transition (EMT) were studied. Anti-ROR1 mAb tagged nanoparticles further confirmed therapeutic efficacy against colon cancer cells, SW480, thus, opening scope for further in vivo studies.

Elsevier eBooks, 2021

Abstract Drug discovery is an arduous, time consuming and expensive process requiring several yea... more Abstract Drug discovery is an arduous, time consuming and expensive process requiring several years and a huge amount of funding. Identifying a potential drug target and suitable lead molecule for drug development are critical steps in the drug discovery process. Among the various methods available for the identification of new lead molecules, structural bioinformatics has a special place. Structural bioinformatics plays a vital role in target validation, active site identification, lead optimization, drug-likeness prediction and stability analysis. The structural bioinformatics helps in identifying and designing novel leads against a selected drug target that could be tested experimentally to check the impact on the biological system.

Medical Oncology, Jul 20, 2017

DNA methyltransferases make use of alternative splicing mechanism to generate various splice vari... more DNA methyltransferases make use of alternative splicing mechanism to generate various splice variants, but their role(s) in modulating DNA methylation patterns in the cells is unclear. Notably, DNMT3B alone contains nearly 40 different splice variants. In this study, we have identified a novel splice variant of DNMT3B, which lacks exon 7 and 10 from leukemic cell lines which we termed as DNMT3B9. The exon 7 codes for the major part of PWWP domain, and exon 10 inclusion serves as a pluripotent marker. By quantitative RT-PCR using exon-exon junction-specific primers, we showed higher level of DNMT3B9 transcripts in several leukemic cell lines. However, DNMT3B9 expression was less in other tested cancer cell lines indicating that DNMT3B9 might serve as a leukemic-specific biomarker. Surprisingly, endogenous protein for DNMT3B9 was not detected in leukemic cells suggesting the unidentified RNA-related function(s) for DNMT3B9. In addition, we showed that DNMT3B9 protein lacks PWWP domain is less stable compared to other DNMT3B variants which contain PWWP domain through computational predictions and by cycloheximide half-life experiment. Taken together, we demonstrated the existence of novel leukemic-specific splice variant of DNMT3B and provide the evidence for the role of PWWP domain in the stability of DNMT3B. The findings reported here have relevance in epigenetic therapy, which is aimed to target the DNMT3B in cancer cells.

Bioorganic Chemistry, May 1, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

European Journal of Pharmaceutical Sciences, Aug 1, 2003

Potential of piperine, an active alkaloid of black and long peppers, to increase the bioavailabil... more Potential of piperine, an active alkaloid of black and long peppers, to increase the bioavailability of drugs in humans is of great clinical significance owing to its omnipresence in food. In an attempt to further study the reported differences in its metabolism in rats and humans, a new major urinary metabolite was detected in rat urine and plasma using HPLC. The metabolite was partially purified using reverse phase column chromatography on Sephadex((R))-LH 20 and characterized as 5-(3, 4-methylenedioxy phenyl)-2E,4E-pentadienoic acid-N-(3-yl propionic acid)-amide with the help of LC/NMR/positive ESI-MS studies. Complete mass fragmentation pattern could be assigned with MS/MS studies. The metabolite has a unique structure compared to the previously reported metabolites in that it retains methylenedioxy ring and conjugated double bonds while the piperidine ring is modified to form propionic acid group. Mechanism of formation of the metabolite by oxidation and cleavage of piperidine ring is proposed. Kidney appears to be the major excretion route for piperine metabolites in rats as no metabolite could be detected in feces.

Current Computer-Aided Drug Design, 2021

Background: A multi-objective genetic algorithm for De novo drug design (MoGADdrug) has been prop... more Background: A multi-objective genetic algorithm for De novo drug design (MoGADdrug) has been proposed in this paper for the design of novel drug-like molecules similar to some reference molecules. The algorithm developed accepts a set of fragments extracted from approved drugs and available in fragment libraries and combines them according to specified rules to discover new drugs through the in-silico method. Method: For this process, a genetic algorithm has been used, which encodes the fragments as genes of variable length chromosomes and applies various genetic operators throughout the generations. A weighted sum approach is used to simultaneously optimize the structural similarity of the new drug to a reference molecule as well as its drug-likeness property. Results: Five reference molecules namely Lidocaine, Furano-pyrimidine derivative, Imatinib, Atorvastatin and Glipizide have been chosen for the performance evaluation of the algorithm. Conclusion: Also, the newly designed mol...

International Journal of Intelligent Systems and Applications, 2019

Swarm intelligence algorithms are designed to mimic the natural behaviors of living organisms. Th... more Swarm intelligence algorithms are designed to mimic the natural behaviors of living organisms. The birds, animals and insects exhibit extraordinary problem solving behaviors and intelligence when living in colonies or groups. These unique behaviors form the basis for the design of the Metaheuristic which are helpful in solving several real-life combinatorial optimization problems. Monkey algorithm is developed based on the unique behaviors of monkeys such as mountain and tree climbing, jumping, watching and somersaulting. This paper reports for the first time the design and development of Multi-objective Monkey Algorithm (MoMA) and its use for the design of molecules with optimal drug-like properties. Finally, the performance of the proposed MoMA for Drug design (MoMADrug) is compared with the previously disclosed Multi-objective Genetic algorithm (MoGADdrug) for the design of drug-like molecules.

Medical oncology (Northwood, London, England), 2017

DNA methyltransferases make use of alternative splicing mechanism to generate various splice vari... more DNA methyltransferases make use of alternative splicing mechanism to generate various splice variants, but their role(s) in modulating DNA methylation patterns in the cells is unclear. Notably, DNMT3B alone contains nearly 40 different splice variants. In this study, we have identified a novel splice variant of DNMT3B, which lacks exon 7 and 10 from leukemic cell lines which we termed as DNMT3B9. The exon 7 codes for the major part of PWWP domain, and exon 10 inclusion serves as a pluripotent marker. By quantitative RT-PCR using exon-exon junction-specific primers, we showed higher level of DNMT3B9 transcripts in several leukemic cell lines. However, DNMT3B9 expression was less in other tested cancer cell lines indicating that DNMT3B9 might serve as a leukemic-specific biomarker. Surprisingly, endogenous protein for DNMT3B9 was not detected in leukemic cells suggesting the unidentified RNA-related function(s) for DNMT3B9. In addition, we showed that DNMT3B9 protein lacks PWWP domain...

European Journal of Pharmaceutical Sciences, 2003

Potential of piperine, an active alkaloid of black and long peppers, to increase the bioavailabil... more Potential of piperine, an active alkaloid of black and long peppers, to increase the bioavailability of drugs in humans is of great clinical significance owing to its omnipresence in food. In an attempt to further study the reported differences in its metabolism in rats and humans, a new major urinary metabolite was detected in rat urine and plasma using HPLC. The metabolite was partially purified using reverse phase column chromatography on Sephadex((R))-LH 20 and characterized as 5-(3, 4-methylenedioxy phenyl)-2E,4E-pentadienoic acid-N-(3-yl propionic acid)-amide with the help of LC/NMR/positive ESI-MS studies. Complete mass fragmentation pattern could be assigned with MS/MS studies. The metabolite has a unique structure compared to the previously reported metabolites in that it retains methylenedioxy ring and conjugated double bonds while the piperidine ring is modified to form propionic acid group. Mechanism of formation of the metabolite by oxidation and cleavage of piperidine ring is proposed. Kidney appears to be the major excretion route for piperine metabolites in rats as no metabolite could be detected in feces.

ChemInform, 2004

Isoindole derivatives Isoindole derivatives R 0140 Synthesis of 4-(1-Oxo-isoindoline)-, 4-(5,6-Di... more Isoindole derivatives Isoindole derivatives R 0140 Synthesis of 4-(1-Oxo-isoindoline)-, 4-(5,6-Dimethoxy-1-oxo-isoindoline) and 4-Acetamido-Substituted Phenoxy-3-amino-propane Derivatives and Their β 1-, β 2-Adrenergic Receptor Binding Studies.-The β-adrenoceptor binding affinity and selectivity of the synthesized compounds (V) are tested. All the tested compounds (V) exhibit better cardioselectivity than the standard cardioselective β-blocker atenolol.

Acta Crystallographica Section E Structure Reports Online, 2002