Department Of Biochemistry And Microbial Sciences

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Author: search.filters.author.Singh, Atul KumarSubject: search.filters.subject.apoptosis

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    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, Shashank
    Apoptosis 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.
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    Five-Decade Update on Chemopreventive and Other Pharmacological Potential of Kurarinone: a Natural Flavanone
    (Frontiers Media S.A., 2021-09-27T00:00:00) Kumar, Shashank; Prajapati, Kumari Sunita; Shuaib, Mohd; Kushwaha, Prem Prakash; Tuli, Hardeep Singh; Singh, Atul Kumar
    In the present article we present an update on the role of chemoprevention and other pharmacological activities reported on kurarinone, a natural flavanone (from 1970 to 2021). To the best of our knowledge this is the first and exhaustive review of kurarinone. The literature was obtained from different search engine platforms including PubMed. Kurarinone possesses anticancer potential against cervical, lung (non-small and small), hepatic, esophageal, breast, gastric, cervical, and prostate cancer cells. In vivo anticancer potential of kurarinone has been extensively studied in lungs (non-small and small) using experimental xenograft models. In in vitro anticancer studies, kurarinone showed IC50 in the range of 2�62��M while in vivo efficacy was studied in the range of 20�500�mg/kg body weight of the experimental organism. The phytochemical showed higher selectivity toward cancer cells in comparison to respective normal cells. kurarinone inhibits cell cycle progression in G2/M and Sub-G1 phase in a cancer-specific context. It induces apoptosis in cancer cells by modulating molecular players involved in apoptosis/anti-apoptotic processes such as NF-?B, caspase 3/8/9/12, Bcl2, Bcl-XL, etc. The phytochemical inhibits metastasis in cancer cells by modulating the protein expression of Vimentin, N-cadherin, E-cadherin, MMP2, MMP3, and MMP9. It produces a cytostatic effect by modulating p21, p27, Cyclin D1, and Cyclin A proteins in cancer cells. Kurarinone possesses stress-mediated anticancer activity and modulates STAT3 and Akt pathways. Besides, the literature showed that kurarinone possesses anti-inflammatory, anti-drug resistance, anti-microbial (fungal, yeast, bacteria, and Coronavirus), channel and transporter modulation, neuroprotection, and estrogenic activities as well as tyrosinase/diacylglycerol acyltransferase/glucosidase/aldose reductase/human carboxylesterases 2 inhibitory potential. Kurarinone also showed therapeutic potential in the clinical study. Further, we also discussed the isolation, bioavailability, metabolism, and toxicity of Kurarinone in experimental models. � Copyright � 2021 Kumar, Prajapati, Shuaib, Kushwaha, Tuli and Singh.