Synthesis and evaluation of inhibitory potentials of microbial biofilms and quorum-sensing by 3-(1,3-dithian-2-ylidene) pentane-2,4-dione and ethyl-2-cyano-2-(1,3-dithian-2-ylidene) acetate

Abstract

The virulence and resistance of pathogenic microorganisms are promoted by quorum-sensing (QS) mediated traits and biofilms. The development of antimicrobial agents which can reduce the incidence of microbial resistance by disrupting the establishment of biofilms and QS, constitute a suitable strategy to reduce the emergence of pathogenic strains that are resistant to antibiotics. In this study, 3-(1,3-dithian-2-ylidene) pentane-2,4-dione (1) and ethyl-2-cyano-2-(1,3-dithian-2-ylidene) acetate (2) were successfully synthesized and characterized using EIMS, 1H NMR and 13C NMR techniques. On S. aureus, both compounds had MIC (minimal inhibitory concentrations) of 0.625 mg/mL while on E. coli and C. albicans, compound 2 showed higher activity than compound 1. All compounds inhibited formation of biofilms by C. albicans and S. aureus at sub-MIC with compound 1 being more active than compound 2. On E. coli, only compound 1 inhibited biofilm formation. Violacein production of violacein in C. violaceum CV12472 and quorum sensing in C. violaceum CV026 were inhibited indicating that the compounds could block signal production and reception. Anti-quorum sensing at sub-MIC concentrations revealed by inhibition zones were 13.0±0.5 mm and 8.0±0.5 mm at MIC and MIC/2 respectively for compound 1 and for compound 2, they were 11.5±0.4 mm and 7.5±0.0 mm at MIC and MIC/2 respectively. Concentration-dependent swarming motility was exhibited by both compounds with compound 1 slightly more active than compound 2. The results indicate that the organosulphur compounds could be suitable candidates for modern antibiotics.