Synthesis, antimicrobial evaluation, HPLC-based compound accumulation and docking studies of 2-methoxybenzoyl thioureas

In this study, we presented the synthesis, antimicrobial activity, High Performance Liquid Chromatography (HPLC)-based compound accumulation and molecular docking of 2-methoxybenzoyl substituted thiourea derivatives. The antimicrobial activity of a total of eight synthesized compounds was evaluated against seven species of bacteria and fungi. HPLC-based compound accumulation assay, molecular docking, in silico toxicity and ADME analyses were performed for selected compounds for further evaluation of compound activity relationship. The compounds exhibited greater activity against fungi than bacteria, with compounds <b>1b</b>, <b>1c</b>, <b>1d</b>, and <b>1g</b> showing particularly strong activity against <i>Candida</i> species. Compounds <b>1a</b>, <b>1b</b>, <b>1d</b>, and <b>1h</b> that had varying biological activities were selected for further analyses. Compounds <b>1a</b>, <b>1b, 1d</b>, and <b>1h</b> accumulated intracellularly reaching up to 36.77% within 1 hours. Molecular docking studies revealed compatible interactions among the compounds in comparison to their varying biological activities. Additionally, all compounds had low toxicity and showed no physicochemical violations when compared to Lipinski’s rule of five. The results suggest that optimizing the position of substituents on the phenyl rings of acyl thioureas could enhance the antimicrobial activity of our compounds.