engleski

Quaternary ammonium salts differing in the substituent at position 3 of quinuclidine ring : synthesis and antimicrobial activity

Quinuclidine is part of the structure of a number of natural physiologically active compounds and some synthetic drugs. Quinuclidine easily forms quaternary ammonium salts and many of them due to the antibacterial activities were used for antiseptic, disinfectants and a variety of clinical purposes. In this study novel ammonium salts bearing quinuclidine moiety were synthesized and evaluated for their antibacterial and antifungal activities. These activities were measured in selected homologues (3-hydroxy- or 3-chloroquinuclidine) with different N-benzyl substitutent at para-position (p-bromo, p-chloro and p-nitro) in order to determine basic structure-antimicrobial activity relationship. Structure of the synthesized compounds was elucidated by 1H NMR, 13C NMR and IR spectral data. These compounds were screened against three gram-positive and three gram-negative bacterial, as well fungal strains by agar disc diffusion method. The antimicrobial activity was investigated by broth microdilution method to determine the minimum inhibitory concentrations of tested compounds.One of the newly synthesized compounds displayed most potent inhibitory activity with MIC values of 6.25, 3.12, 3.12 μg mL-1 against E. coli, P. aeruginosa and C. sakazakii respectively. Compound with 3-hydroxy substituent on the quinuclidine ring and p-chlorobenzyl substituent was found to be the most superior compounds especially against P. aeruginosa which MIC value was 160-fold better than gentamicin. The similar compound with the different substituent on position 3 of the quinuclidine ring displayed excellent activity against B. cereus with a MIC value 2.5-fold lower than gentamicin. Moreover, the antifungal profiles of these compounds were found to be most potent. Structure- activity relationship studies revealed that substituent at position 3 of quinuclidine ring as well as p-substituent at the benzyl ring have a significant effect on the antimicrobial activity of the newly synthesized quaternary ammonium salts.

synthesis ; quaternary ammonium salts ; antimicrobial activity

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