Department Of Biochemistry And Microbial Sciences
Permanent URI for this communityhttps://kr.cup.edu.in/handle/32116/23
Browse
3 results
Search Results
Item Flavonoids as emerging notch signaling pathway modulators in cancer(Taylor and Francis Ltd., 2023-04-21T00:00:00) Singh, Atul Kumar; Kumar, ShashankNotch signaling is an evolutionary conserved pathway important for the developmental processes and implicated in the tumor formation. Notch signaling pathway (NSP) inhibitors have been tested in clinical trials alone or in combination with the chemotherapy but none got clinical approval due to severe toxicity in patients. Flavonoids inhibit NSP by inhibiting notch receptor cleavage and/or inhibiting transcriptional regulation by Notch intracellular domain (NICD). Interestingly, some flavonoids are reported to inhibit NSP by mediating the microRNA expression. NSP inhibitory flavonoid(s) in combination with standard therapy is might be an effective strategy in cancer treatment. � 2023 Informa UK Limited, trading as Taylor & Francis Group.Item Discovery of Natural Anti-Apoptotic Protein Inhibitor Using Molecular Docking and MM-GBSA Approach: An Anticancer Intervention(AMG Transcend Association, 2022-12-27T00:00:00) Dey, Sarbjit; Singh, Atul Kumar; Kumar, ShashankApoptosis is a programmed molecular phenomenon in normal cells, and "evading apoptosis" is a hallmark of cancer. Overexpression of anti-apoptotic BCL-2 promotes cancer cell survival, leading to tumor formation, its maintenance and progression, and further chemoresistance. Therefore, BCL-2 is considered an exciting drug target in clinical studies. The Cip/Kip family protein p21, which acts as an inhibitor of cyclin-CDK complexes, can also exert anti-apoptotic function and thus be involved in cancer initiation and progression. Preliminary research suggests that Piper chaba phytochemical(s) possess anticancer activity, but the underlying mechanism is yet to be established. For the first time, we explored Piper chaba phytochemicals for their anti-apoptotic protein (BCL-2 and p21) inhibition potential using molecular docking and MM-GBSA experiments. UC2288 and Venetoclax were known standards for BCL-2 and p21 proteins, respectively. We also explored the pharmacokinetics and drug-likeness properties of lead molecules using the SwissADME web tool. A total of 45 P. chaba phytochemicals were identified from published literature and docked at the drug-binding site of target proteins. Chabamide F, Piperchabaoside B, Piperundecalidiene, and Chabamide G showed ? binding affinity (-9.0 kcal/mole) than UC2288, while Brachystamide B showed lower binding affinity (-9.7 kcal/mole) than Venetoclax. MM-GBSA results revealed Chabamide F has a higher binding affinity for p21 than the standard compound. Therefore, P. chaba phytoconstituents qualify for further experiments on the drug discovery process to target anti-apoptosis proteins in cancer cells. � 2022 by the authors.Item Naringin dihydrochalcone potentially binds to catalytic domain of matrix metalloproteinase-2: molecular docking, MM-GBSA, and molecular dynamics simulation approach(Taylor and Francis Ltd., 2022-09-01T00:00:00) Singh, Atul Kumar; Kumar, ShashankMatrix metalloproteinase-2 (MMP2), an extracellular matrix remodulating protein�s increased activity causes cancer-metastasis. Potential MMP2 inhibitors showed sever side-effects in clinical trials. Present study is focused on identification natural MMP2 inhibitor by applying molecular docking, MM-GBSA binding energy estimation and molecular dynamics (MD) simulations. Commercially available flavonoid compound library was used to screen the molecules potentially binding with catalytic domain of MMP2 protein compared to standard MMP2 inhibitor ARP100. Naringin dihydrochalcone (NDC) showed interaction with the important residues (His120, Leu82 and Val117) present at the MMP2 catalytic domain in comparison to known inhibitor ARP100 (dock score ? ?13 and ?8 kcal/mole respectively). Lower ligand-protein binding energy (-67.31 kcal/mole) obtained in MM-GBSA and the MD simulation trajectory analysis showed significant stable and energetically favourable binding of NDC at the catalytic site of MMP2. In conclusion, anti-metastatic potential of NDC should be validated in in�vitro and in�vivo experiments. � 2022 Informa UK Limited, trading as Taylor & Francis Group.