ABSTRACT
Objective: To design and synthesize novel dithiolopyrrolone derivatives with antibacterial activity. Methods: Fourteen N-aryldithiolopyrrolone derivatives with 6-amino-4H-[1,2]dithiolo[4,3-b]pyrrol-5-one skeleton were synthesized via amidation and nucleophilic substitution reactions. The in vitro antimicrobial activity against Staphy- lococcus aureus was assayed for all of the synthesized fourteen derivatives by the paper disk diffusion method. For select- ed compounds,the minimum inhibition concentration on S. aureus was determined and the inhibitory activity on the Esch- erichia coli RNA polymerase(RNAP)was further evaluated. In addition,a predictive investigation for the action mecha- nism of the most potent compound 2i was performed by the molecular docking study on RNAP. Results and Conclu- sion: The structures of the synthesized compounds were confirmed by 1H NMR,13C NMR and ESI-MS. The compound 2i showed a potent antibacterial activity and the molecular docking study revealed the interaction of 2i with the switch re- gion of the bacterial RNA polymerase. Compound 2i might serve as a new lead compound for further optimization into po- tential antibacterial agents.