1-Alkyl-(N,N-dimethylamino)pyridinium bromides: inhibitory effect on virulence factors of Candida albicans and on the growth of bacterial pathogens

A homologous series of 1-alkyl-(N,N-dimethylamino)pyridinium bromides, termed compounds 1-11, was synthesized and studied for antibacterial and antifungal activity. Of these, compound 8, containing a ten-carbon alkyl chain, showed maximum inhibition against all the tested bacterial strains. The highest antibacterial activity using a disc diffusion method was recorded against Mycobacterium smegmatis [zone of inhibition (ZOI): 45.75 +/- 0.25 mm], followed by Escherichia coli, Proteus mirabilis, Vibrio cholerae, Staphylococcus aureus and Salmonella typhi. In addition to antibacterial activity, compounds 3-11 displayed good inhibitory action against the human opportunistic yeast pathogens Cryptococcus neoformans and various Candida spp. The maximum ZOI was observed against Cryptococcus neoformans (51.5 +/- 0.5 mm) using compound 8, with ZOIs of 23.5 +/- 0.5, 32.0 +/- 0.0, 27.75 +/- 0.25 and 41.5 +/- 0.5 mm against Candida albicans, Candida glabrata, Candida tropicalis and Candida krusei, respectively. Furthermore, compound 8 caused inhibition of the candidal yeast hyphae transition at a concentration of 0.29 mu M and also inhibited the secretion of extracellular hydrolytic enzyme such as secreted aspartyl proteinase at subinhibitory concentrations. Compound 8 showed very little haemolytic activity at a concentration of 0.58 mu M (1.315 +/- 0.75%), with its highest haemolytic activity (47.806 +/- 2.32%) observed at a concentration of 2.9 mu M.