Benzimidazole-hydrazone derivatives: Synthesis, in vitro anticancer, antimicrobial, antioxidant activities, in silico DFT and ADMET studies

Abstract

Based on the biologically active heterocycle compounds, a series of new benzimidazole-hydrazone deriva- tives ( 3a-3j ) were synthesized, starting from 4-(6-chloro-1 H -benzimidazol-2-yl) benzohydrazide. The syn- thesized compounds were characterized by 1 H NMR, 13 C NMR, and HRMS spectroscopic methods. The synthesized compounds were preliminarily evaluated for their in vitro antimicrobial, anticancer and an- tioxidant activity. The antimicrobial activity was checked against S. aureus ATCC 29213, E. coli ATCC 25922, and C. albicans ATCC 10231 by micro-dilution method. The findings exhibited that the compounds pos- sessed moderate antimicrobial potential. The compounds were also checked for their in vitro anticancer activities against HT-29 (colorectal cancer cell line) using the MTT assay. It was observed that all the compounds 3a-3j showed weak antiproliferative activity against HT-29 cells. The compounds were also analyzed for their antioxidant capacity by Tas & Tos activity. The compound 3d showed a high anti- oxidative effect with 30.81 μmol H O 2 2 Equiv./L value. The lowest energy state of compound 3d was real- ized in DMSO medium by using the B3LYP method at 6–311G (d,p) level, the optimized geometry of it is about 0.50 and 17 kcal/ mol more stable than in other solvents and the gas phase, respectively. The lower E = 3.563 eV indicates the higher reactivity of compound 3d , this is compatible with biological experi- mental data and shows high antioxidant property of the compound. In silico ADMET studies of compound 3d were performed. Indexing of the X-ray powder diffraction pattern was performed for compound 3a .