Dihydrobenzoimidazothiazoles as novel anti-infective agents: Synthesis, biological evaluation and docking studies

Finding safer, more powerful and more effective molecules is urgently needed given the rising threat of infectious diseases. Benzoimidazothiazole are a novel class of small molecules that have not been studied on a variety of pharmacological targets. In this report, we discussed novel dihydrobenzo-imidazothiazole scaffold as promising anti-infective agents. Commercially available 1,3-cyclohexane-diones (1a-h) were brominated before being condensed with thiourea to produce 2-amino-5,6-dihydrobenzo[d]thiazol-7(4H)-ones (3a-h) in excellent yields. Compounds 3a-h were cyclized with 2-bromo-1-(5-chlorothiophen-2-yl)ethan-1-one (4) to produce 2-(5-chlorothiophen-2-yl)-6,7-dihydrobenzo[d]Imidazo [2,1-b]thiazol-8(5H)-ones (5a-h). When synthetic analogues 3a-h and 5a-h were examined for biological activity, they showed effective inhibition against the tested antiviral and antibacterial strains. Two analogues, 3h (CC50: >300 mu M, IC50= 8.3 mu M, SI = >36) and 5h (CC50: >300 mu M, IC50= 4.1 mu M, SI = >73) had high levels of virus-inhibiting action when tested against the pandemic influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells with favorable toxicity profile. Among the substances tested against bacterial strains, 3d inhibited Typhi, Subtills, and Mutans bacteria with MICs of 0.78 mu M and E. coli with MICs of 1.56 mu M against standard streptomycin (MIC:1.56 mu M). The novel analogues' physiochemical and molecular docking tests revealed promising pharmacological profiles for further structural optimization and drug development.