School Of Basic And Applied Sciences

Permanent URI for this communityhttps://kr.cup.edu.in/handle/32116/17

Browse

Author: search.filters.author.Ratre, PoojaSubject: search.filters.subject.Molecular docking

Search Results

Now showing 1 - 2 of 2
  • No Thumbnail Available
    Item
    De novo designing, assessment of target affinity and binding interactions against aromatase: Discovery of novel leads as anti-breast cancer agents
    (Springer, 2020-11-13T00:00:00) Verma, Sant Kumar; Ratre, Pooja; Jain, Akhlesh Kumar; Liang, Chengyuan; Gupta, Ghanshyam Das; Thareja, Suresh
    Aromatase inhibitors (AIs) have been emerged as promising anti-cancer agents for the treatment of hormone dependent breast cancer (HDBC) in women because of their excellent ability of inhibiting oestrogen synthesis. Here, we have implicated structure-based comprehensive approaches to discover novel drug/lead-like AIs. The molecular modelling and energy optimization were performed using Chem Office package. The e-LEA3D web server was used to design novel drug/lead-like AIs as well as generation of ADME/drug-likeness parameters. Target binding affinities and mode of binding interactions were mapped using Molegro Virtual Docker (MVD) to re-optimize the best de novo generated molecules. We have successfully designed novel AIs (compounds 1�7) using de novo technique performed on e-LEA3D. All the designed molecules were found optimum drug-like candidates based on various in silico screening parameters including �rule of five�. The energy optimized conformers of generated molecules (1�7) were docked in the active site, corresponding to co-crystallized androstenedione (ASD), of aromatase to predict ligand-target binding affinity and their binding interactions. The molecules (1�7) showed comparable to higher binding affinity towards aromatase with MolDock Score ranges from ? 134.881 to ? 152.453�Kcal/mol as compared with natural substrate ASD (? 128.639�Kcal/mol) and standard letrozole (? 136.784�Kcal/mol). The de novo designed molecules (1�7) can be developed as novel AIs, and their binding properties can be used for the further designing of newer AIs by medicinal chemists. � 2020, Springer Science+Business Media, LLC, part of Springer Nature.
  • No Thumbnail Available
    Item
    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.