STUDY OF In-silico ADMET, MOLECULAR DOCKING, AND STABILITY POTENTIAL OF SYNTHESIZED NOVEL TETRAZOLE BEARING CURCUMIN DERIVATIVES AND EVALUATION OF THEIR ANTICANCER POTENTIAL ON PANC-1 CELL LINES
G. Krishnamurthy, Lairikyengbam Deepti Roy, J. Kumar, P. Gour, S. Arland, M. Prabu, Srinivasa Gr, Shreenivas Mt
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引用次数: 1
Abstract
Amplified expression of mutations in proteins is an important hallmark of malignant cancer. In all RAS-mutant human cancers, pancreatic ductal adenocarcinoma (PDAC) is considered the most RAS-fanatic cancer, with a frequency of 100% KRAS (Kirsten rat sarcoma virus) mutation. In the present work, curcumin, a dietary phytochemical, was used to design a series of novel curcumin analogues aiming to regulate KRAS protein. The molecular docking study revealed the ligand efficacy and binding affinity of designed curcumin analogues against target proteins. Drug-like behaviour and ADMET (absorption, distribution, metabolism, excretion, and toxicity) prediction of identified molecules were done, and most of the pharmacokinetic parameters were found to be quite satisfactory and within an acceptable range. Three of the most potent drug candidates have been synthesized and characterized by FTIR, 1HNMR, and LC-MS spectral analysis. Results of the in vitro anti-proliferative activities of curcumin analogues showed persuasive anticancer activity against the PANC-1 cell lines. The present study will be helpful in exploring the new series of cogent curcumin analogues as anticancer agents.
期刊介绍:
RASĀYAN Journal of Chemistry [RJC] signifies a confluence of diverse streams of chemistry to stir up the cerebral powers of its contributors and readers. By introducing the journal by this name, we humbly intent to provide an open platform to all researchers, academicians and readers to showcase their ideas and research findings among the people of their own fraternity and to share their vast repository of knowledge and information. The journal seeks to embody the spirit of enquiry and innovation to augment the richness of existing chemistry literature and theories. We also aim towards making this journal an unparalleled reservoir of information and in process aspire to inculcate and expand the research aptitude.