Browsing by Author "Revanasiddappa, B.C."

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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.
Hydrazineyl-linked imidazole[1,2-a]pyrimidine-thiazole hybrids: design, synthesis, and in vitro biological evaluation studies
(Royal Society of Chemistry, 2025) Dinesha, P.; Naik, S.; Udayakumar, U.; Revanasiddappa, B.C.; Ranjan, V.; Veeranagaiah, N.S.
This research work details the use of a molecular hybridization technique to create a library of four series of hydrazineyl-linked imidazo[1,2-a]pyrimidine-thiazole derivatives. The structure of one of the final products, K2, was validated using single-crystal X-ray diffraction. Twenty-six novel hybrid molecules (K1-K26) were synthesized and tested for activity against the mycobacterium tuberculosis H37Rv strain. Three compounds (K1, K2, and K3) demonstrated significant inhibitory efficacy, with a MIC value of 1.6 ?g mL?1. The target compounds also showed significant antibacterial activity against four bacterial strains, namely S. aureus, E. coli, B. subtilis, and P. aeruginosa. In cytotoxicity studies using VERO cells, the potent anti-TB compounds (K1, K2, and K3) showed non-toxic profiles. Furthermore, in silico ADME assessment results, molecular docking (against InhA and CYP121), and DFT studies revealed the active compounds' significant potential as scaffolds for novel antitubercular medicines. © 2025 The Royal Society of Chemistry.
In Silico Studies of (Z)-3-(2-Chloro-4-Nitrophenyl)-5-(4-Nitrobenzylidene)-2-Thioxothiazolidin-4-One Derivatives as PPAR-γ Agonist: Design, Molecular Docking, MM-GBSA Assay, Toxicity Predictions, DFT Calculations and MD Simulation Studies
(World Scientific, 2024) Gowdru Srinivasa, M.G.; Naik, S.; Udayakumar, U.; Mehta, C.H.; Nayak, U.Y.; Revanasiddappa, B.C.
Diabetes mellitus, a metabolic disorder, arises from insufficient insulin levels or increased insulin resistance. An alternative approach to address this pathogenesis involves targeting PPAR-γ, which activates glucose homeostasis and improves peripheral glucose utilization. In this study, we aimed to investigate the designed 2-thioxothiazolidin-4-one derivatives (T1-25) and assess their potential as PPAR-γ regulators by an in silico approach. Physicochemical properties and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiles were evaluated. Docking studies were performed using Schrödinger software, with the protein target being PPAR-γ (PDB ID: 2ZNO). Additionally, MD simulation studies were conducted, and the key interactions in the protein-ligand complexes were identified. The results demonstrate the drug-likeness of compounds T11, T24 and T25, with docking scores of -7.953 kcal/mol, -7.973 kcal/ mol and -8.212 kcal/mol, respectively, and exhibit significant activity against PPAR-γ agonist and compared with the standard drug Pioglitazone (-7.367 kcal/mol). The density functional calculations were also performed to determine the geometrical properties, thermal parameters, chemical reactivity descriptors and molecular electrostatic potential of the compounds using the B3LYP functional and 6-31G++ basis sets. The energy difference between the highest occupied molecular orbitals and lowest unoccupied molecular orbitals for all the investigated compounds is in the range of 2.8-3.4 eV which allows for easy transfer of electrons and reactivity. Further research and development of these designed compounds could contribute to the advancement of effective antidiabetic treatments. © 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.