Browsing by Author "Dixit, S.R."

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Benzothiazole derivatives as p53-MDM2 inhibitors: in-silico design, ADMET predictions, molecular docking, MM-GBSA Assay, MD simulations studies
(Taylor and Francis Ltd., 2025) Shridhar Deshpande, N.; Naik, S.; Udayakumar, U.; Ghate, S.D.; Dixit, S.R.; Awasthi, A.; Revanasiddappa, B.C.
Breast cancer stands as the most prevalent malignancy among the female populace. One of the pivotal domains in the therapeutic landscape of breast cancer revolves around the precise targeting of the p53-MDM2 inhibitory pathway. The advent of p53-MDM2 inhibition in the context of developing treatments for breast cancer marks a significant stride. In the quest for enhancing the efficacy of p53-MDM2 inhibition against breast cancer, a new series of benzothiazole compounds (B1-B30) was designed through in-silico methodologies in the present work. Using Schrodinger Maestro, the compounds underwent molecular docking assessments against the p53-MDM2 target (PDB: 4OGT). Compared to reference compounds, B25 and B12 exhibited notably elevated glide scores. Extensive in-silico studies, including ADMET and toxicity evaluations, were performed to predict pharmacokinetics, drug likeness, and toxicity. All compounds adhered to Lipinski criteria, signifying favorable oral drug properties. The MM-GBSA analysis indicated consistent binding free energies. Molecular dynamics simulations for B25 over 200 ns assessed complex stability and interactions. In summary, these compounds exhibit potential for future cancer therapy medication development. © 2023 Informa UK Limited, trading as Taylor & Francis Group.
Exploring Plant-Derived Bioactive Compounds in Olea Europaea L. Leaves as Potent Inhibitors of PTP-1B Using an In silico Approach
(World Scientific, 2024) Deshpande, N.S.; Wagh, S.; Sharma, A.P.; Ramesh, A.; Mahindra; Lavanya; Moksha, B.S.; Divyashree; Disha; Dixit, S.R.; Singh, D.; Bidye, D.P.; Revanasiddappa, B.C.
In this study, we focus on exploring the medicinal potential of Olea Europaea L., a commonly used plant with diverse indigenous medicinal applications. The main aim is to identify promising phytoconstituents from Olea Europaea L. leaves that can act as inhibitors for the PTP-1B target, utilizing an in silico approach. The phytoconstituents were sourced from the IMMPAT database, and molecular docking was employed to assess their binding affinities. The docking results revealed that rutin (-10.05 kcal/mol) and quercetin (-8.28 kcal/mol) displayed the highest binding scores against PTP-1B, outperforming reference compounds. Furthermore, MM-GBSA calculations indicated favorable free binding energy. To ensure stability, 200 ns Molecular Dynamics simulations were conducted on the 2QBS-Rutin complex. The results revealed that the 2QBS-Rutin complex showed stable conformation throughout the simulation, maintaining consistency with RMSD values below 1 Å. This study highlights rutin and quercetin as promising phytoconstituents from Olea Europaea L. leaves, demonstrating potent-binding affinities against PTP-1B inhibitors. © 2024 World Scientific Publishing Company.
Synthesis, Molecular Docking, MD Simulation and Evaluation of Anticancer Activity of Novel 1,3,4-Oxadiazole Derivatives against Ehrlich Ascites Carcinoma (EAC) Cell Lines
(World Scientific, 2024) Deshpande, N.S.; Naik, S.; Udayakumar, U.; Prabhu, A.; Rani, V.; Dixit, S.R.; Singh, D.; Revanasiddappa, B.C.
In this study, a new series of 1,3,4-oxadiazole derivatives (3a- 3h) was synthesized, characterized using various analytical techniques (FT-IR, 1H- and 13C-NMR, mass spectrometry), and tested for their effectiveness against Ehrlich's Ascites Carcinoma (EAC) cell lines in vitro. After 48 h of exposure to these test compounds, the EAC cells exhibited a dose-dependent reduction in their viability. Among the tested compounds, 3b and 3e demonstrated the most potent anticancer effects, with IC50 values of 352.69 μM and 177.44 μ M, respectively. Consequently, these compounds were chosen for further investigation into their mechanisms of action on EAC cell lines. The assessment included the induction of apoptosis and the analysis of DNA damage, which were evaluated using fluorescence staining and the comet assay. These assessments revealed distinctive apoptotic characteristics such as nuclear fragmentation, cytoplasmic shrinkage and DNA damage. As a result, these compounds hold promise as potential anticancer agents. The study also delved into the binding affinities of these compounds through molecular docking analysis, and the findings showed that compounds 3b and 3e exhibited a strong binding affinity with the receptor Transforming Growth Factor-Beta Receptor I (TGF-βRI) kinase (PDB ID: 1PY5), surpassing the reference compound 5-fluorouracil. Additionally, calculations related to Molecular Mechanics Generalized Born Surface Area (MM-GBSA) indicated favorable free binding energy. The compounds also displayed acceptable ADMET properties. To validate the stability of the bond between compounds 3b and 3e with the 1PY5 receptor, a molecular dynamics simulation lasting 100 ns was carried out. © 2024 World Scientific Publishing Company.