Design, Synthesis, Molecular Docking, Antitubercular, Antimicrobial and Antioxidant Studies of Some Novel 3-(((1H-Benzo[d]imidazol-2- yl)methyl)thio)-5H-[1,2,4] Triazino[5,6-b]indole Derivatives

Abstract

A series of novel 3-(((1H-benzo[d]imidazol-2-yl)methyl)thio)-5H-[1,2,4]triazino[5,6-b]indole derivatives (3a-3j) were synthesized by reacting different substituted 5H-[1,2,4]triazino[5,6-b]indole-3-thiols with substituted (2-chloromethyl)-1H-benzo(d)imidazoles in the presence of KOH and water in good yields. The structures of the newly synthesized compounds were confirmed by spectroscopic techniques such as 1H-NMR, 13C-NMR, IR and mass spectrometry. The in-vitro antitubercular activity of the synthesized compounds was evaluated against Mycobacterium tuberculosis (Mtb) H37Rv (ATCC 27294) using MABA (Microplate Alamar Blue Assay) method. Compounds 3b, 3c, and 3i showed good antitubercular activity against Mtb with MIC value of 6.25 ± 0.00 μg/mL. Also, the in-vitro antimicrobial activities of the compounds were evaluated against various bacterial and fungal strains using the two-fold serial dilution technique and most of the compounds exhibited moderate activities with MIC values in the range of 63.33 ± 1.44 to >500 ????g/mL against the tested microorganisms. The compounds (3a-3j) were also tested for their in-vitro antioxidant activities by DPPH radical scavenging activity method and among the series, compounds 3e, 3a, and 3g exhibited strong antioxidant activity with IC50 values of 10.85 ± 0.05, 12.18 ± 0.13 and 12.57 ± 0.17????g/mL respectively compared to the standard ascorbic acid (IC50 value, 5.85 ± 0.04 ????g/mL). Further, molecular docking studies were performed to investigate the binding affinities as well as the interaction of these compounds with Mtb InhA target protein. In-silico ADME predictions showed that all the synthesized compounds have drug-like properties and exhibited good oral bioavailability.