Synthesis and Evaluation of New 1,3,4-Thiadiazole-Benzimidazole Hybrids as Potent Antibacterial Agents

Abstract

Owing to the rapid rise in antibiotic resistance, infectious diseases have become a serious threat to public health. There is an urgent need to develop new antimicrobial agents with diverse chemical structures and novel mechanisms of action to overcome resistance. In recent years 1,3,4-Thiadiazole benzimidazole hybrids have emerged as a new class of antimicrobial agents. In the current study, we designed and synthesized six new 1,3,4-Thiadiazole-benzimidazole hybrids using nucleophilic substitution reaction between 2-mercapto-1H-benzimidazole (A) with Ethyl chloroacetate to produce compound (B), which then reacted with various 2-Amino-5-(substituted phenyl)-1,3,4-thiadiazole(C1-C6) to yield target compounds (D1-D6) and evaluated them for their antimicrobial activity. Synthesized compounds were characterized and elucidated by IR, 1H and 13C-NMR, spectra. Subsequently, the antibacterial activity of the final target compounds (D1-D6) was examined in vitro against four types of bacterial isolates: two gram-positive (Staphylococcus aureus and Bacillus subtilis) and two gram-negative (Pseudomonas aeruginosa and Escherichia coli). Compounds (D4 and D6) demonstrated promising pharmacological activity in vitro when compared to the standard antibacterial agent Tetracycline.