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

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,1 HNMR, 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.