Synthesis, crystallography, biological activity, and molecular modeling studies of some 3-Aryl-2-(4-(substitutedphenyl)thiazol-2-yl)acrylonitrile derivatives

In this study, a series of 3-aryl-2-(4-(substitutedphenyl)thiazol-2-yl)acrylonitrile derivatives, was synthesized and their structures were elucidated using ¹H/^13CNMR, IR, HRMS and quantum crystallography methods. Ab initio quantum mechanics (QM) was applied to predict their molecular geometry and frontier molecular orbital parameters (FMO) in aqueous medium. Molecular descriptors were calculated to predict their druglikeness. Antimicrobial activities of the synthesized compounds were investigated against Mycobacterium tuberculosis H37Rv strain, various Gram-positive and Gram-negative bacteria, and three Candida spp. were evaluated in vitro using isoniazid, ethambutol, ciprofloxacin, and fluconazole (Diflucan) as reference drugs. Among the tested compounds, 2-(4-(2,4-dichlorophenyl)thiazol-2-yl)-3-(4-(trifluoromethyl)phenyl)acrylonitrile (10) was found to be a promising antifungal agent with a minimum inhibitory concertation (MIC) value of 32 µg/mL against C. parapsilosis. Molecular docking was performed to explain the molecular mechanism of its activity. Based on these findings, the title compounds serve a promising starting point for further structure-activity relationships and medicinal chemistry studies.