Pharmaceutical Sciences and Natural Products - Research Publications

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Author: search.filters.author.Banjare, LaxmiSubject: search.filters.subject.Molecular docking

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    Multifaceted 3D-QSAR analysis for the identification of pharmacophoric features of biphenyl analogues as aromatase inhibitors
    (Taylor and Francis Ltd., 2021-12-29T00:00:00) Banjare, Laxmi; Singh, Yogesh; Verma, Sant Kumar; Singh, Atul Kumar; Kumar, Pradeep; Kumar, Shashank; Jain, Akhlesh Kumar; Thareja, Suresh
    Aromatase, a cytochrome P450 enzyme, is responsible for the conversion of androgens to estrogens, which fuel the multiplication of cancerous cells. Inhibition of estrogen biosynthesis by aromatase inhibitors (AIs) is one of the highly advanced therapeutic approach available for the treatment of estrogen-positive breast cancer. Biphenyl moiety aids lipophilicity to the conjugated scaffold and enhances the accessibility of the ligand to the target. The present study is focused on the investigation of, the mode of binding of biphenyl with aromatase, prediction of ligand-target binding affinities, and pharmacophoric features essential for favorable for aromatase inhibition. A multifaceted 3D-QSAR (SOMFA, Field and Gaussian) along with molecular docking, molecular dynamic simulations and pharmacophore mapping were performed on a series of biphenyl bearing molecules (1�33) with a wide range of aromatase inhibitory activity (0.15�920 nM). Among the generated 3D-QSAR models, the Force field-based 3D-QSAR model (R 2 = 0.9151) was best as compared to SOMFA and Gaussian Field (R 2=0.7706, 0.9074, respectively). However, all the generated 3D-QSAR models were statistically fit, robust enough, and reliable to explain the variation in biological activity in relation to pharmacophoric features of dataset molecules. A four-point pharmacophoric features with three acceptor sites (A), one aromatic ring (R) features, AAAR_1, were obtained with the site and survival score values 0.890 and 4.613, respectively. The generated 3D-QSAR plots in the study insight into the structure�activity relationship of dataset molecules, which may help in the designing of potent biphenyl derivatives as newer inhibitors of aromatase. Communicated by Ramaswamy H. Sarma. � 2021 Informa UK Limited, trading as Taylor & Francis Group.
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    In silico molecular interaction studies of chitosan polymer with aromatase inhibitor: Leads to letrozole nanoparticles for the treatment of breast cancer
    (Bentham Science Publishers, 2020-08-26T00:00:00) Mishra, Keerti; Verma, Sant K.; Ratre, Pooja; Banjare, Laxmi; Jain, Abhishek; Thareja, Suresh; Jain, Akhlesh K.
    Background: It takes a lot more studies to evaluate the molecular interaction of nanoparticles with the drug, their drug delivery potential and release kinetics. Thus, we have taken in silico and in vitro approaches into account for the evaluation of the drug delivery ability of the chitosan nanoparticles. Objective: The present work was aimed to study the interaction of chitosan nanoparticles with appropriate aromatase inhibitors using in silico tools. Further, synthesis and characterization of chitosan nanoparticles having optimal binding energy and affinity between drug and polymer in terms of size, encapsulation efficiency were carried out. Methods: In the current study, molecular docking was used to map the molecular interactions and estimation of binding energy involved between the nanoparticles and the drug molecules in silico. Letrozole is used as a model cytotoxic agent currently being used clinically; hence Letrozole loaded chitosan nanoparticles were formulated and characterized using photomicroscope, particle size analyzer, scanning electron microscope and fourier transform infra-red spectroscopy. Results: Letrozole had the second-highest binding affinity within the core of chitosan with MolDock (-102.470) and Re-rank (-81.084) scores. Further, it was investigated that formulated nanoparticles were having superior drug loading capacity and high encapsulation efficiency. In vitro drug release study exhibited prolonged release of the drug from chitosan nanoparticles. Conclusion: Results obtained from the in silico and in vitro studies suggest that Letrozole loaded nanoparticles are ideal for breast cancer treatment. � 2021 Bentham Science Publishers.