Synthesis of 2-ethylhexyl 5-bromothiophene-2-carboxylates; Antibacterial activities against salmonella typhi, validation via docking studies, pharmacokinetics, and structural features determination through DFT

A new class of thiophene-based molecules of 5-bromothiophene-2-carboxylic acid (1) has been synthesized in current research work. All analogs 4A–4G were synthesized with optimized conditions by coupling reactions of 2-ethylhexyl 5-bromothiophene-2-carboxylate (3) with various arylboronic acids. The results indicated that the majority of compounds showed promising effective in vitro antibacterial activity. Herein, 2-ethylhexyl-5-(p- tolyl) thiophene-2-carboxylate (4F), in particular among the synthesized analogs, showed outstanding antibacterial action (MIC value 3.125 mg/mL) against XDR Salmonella Typhi compared to ciprofloxacin and ceftriaxone. The intermolecular interaction was investigated by using a molecular docking study of thiophene derivatives 4A–4G against XDR S. Typhi. The values of the binding affinity of functionalized thiophene molecules and ciprofloxacin were compared against the bacterial enzyme PDB ID: 5ztj. Therefore, 4F appears to be a promising antibacterial agent and showed the highest potential value. Density functional theory (DFT) calculations were executed to examine the electronic, structural, and spectroscopic features of the newly synthesized molecules 4A–4G.