Design, Synthesis, Characterization, Molecular Docking Studies and Evaluation of Anticancer Activities of Pyrazole Fused Novel Indole-2-One Derivatives

Abstract

In this study, a new series of pyrazole fused novel Indole-2-one derivatives (II-VI_(a-o)) by conventional method via Schiff’s and Mannich base mechanism. Novel 3-(3-((1H-pyrazol-4-yl)imino)-2-oxoindolin-1-yl)-N,3-diphenylpropanamide derivatives were prepared by two steps. In step-1, substituted Isatins were reacts with 4-amino pyrazole via Schiff’s base reaction to give pyrazol-4-yl)imino)-5-chloroindolin-2-one(IV). It can be undergone mannich base reaction with phenylacetamide and substituted benzaldehyde(V) to get title compounds. The synthesized compound’s structure was confirmed by IR, 1H NMR, and Mass spectroscopy. Anticancer activity against two cancer cell lines (MCF-7 and SKOV3) were evaluated using MTT assay method. Compounds II-VI_c and II-VI_f showed broad spectrum anticancer activity on the two tested cell lines with IC50 vales compared with standard. The Doxorubicin used as a standard reference drug. The anticancer activity results shown that compound II-VI_c with IC50 values of20.21±0.021 µg(MCF-7) and 25.97±0.023 µg(SKOV3) and compound II-VI_f with IC50 values of 37.26±0.001µg (MCF-7) and 24.56±0.002µg (SKOV3) respectively. Additionally, Molecular docking studies were conducted to investigate the binding mode, amino acid interactions and free binding energy of these potent derivatives. Notably compounds II-VI_c and f exhibited highest amino acid bonding interactions like PHE: 699, LYS:721, LEU: 764, LEU:694, ASP:831, VAL:702, CYS:773, ARG:817.