Synthesis of Piperidine Conjugated Quinoxalines as Potential Antibiofilm Agents

Abstract

Background: The most common cause of food-borne illness is bacterial or viral contamination. Although there are several therapeutics available to combat these microbes, they lost their efficacy in long-term medication. Because, over a period of time, microbes developed resistance against drugs and this antimicrobial resistance is a serious threat to global public health as a consequence of the widely disseminated and careless use of antimicrobials. Therefore, there is a need to develop some new chemical moieties with a safety factor and better efficacy. A series of substituted N-(1-benzylpiperidin-4- yl)quinoxalin-2-amines (5a-j) (5ab, 5ac) were synthesized and screened for their in vitro antibacterial activity against Salmonella paratyphi, a well-known food-borne pathogen. Methods: Experimental methods, agar diffusion and broth microdilution assays were carried out to evaluate the antibacterial activity of the lead compounds. Further, antibiofilm methods, crystal violet, and MTT assays were subjected to investigate their biofilm inhibition capacity against S. paratyphi. Results: Among the tested compounds, 5b, 5e, 5h, and 5j bearing 4-chloro, 3,4-dimethoxy, 4-methyl and thienyl groups on the phenyl ring of quinoxalines emerged as potential candidates having significant antisalmonella activity. In these four potential candidates, compounds 5b and 5h were effective against Salmonella whereas compounds 5e and 5j effectively inhibited the biofilm formation of Salmonella. Conclusion: N-(1-benzylpiperidin-4-yl)quinoxalin-2-amines (5a-j) (5ab, 5ac) were synthesized and evaluated for antisalmonella activity against S. paratyphi. Among the series of compounds, four compounds significantly showed good activity and emerged as antibacterial agents for further studies in the future.