Repositioning of 8-hydroxyquinoline derivatives as a new promising candidate for combating multidrug resistant Neisseria gonorrhoeae

Abstract

© 2018, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved. The multidrug resistance of Neisseria gonorrhoeae becomes a public health problem worldwide, especially the strain H041 that showed the decrease susceptibility to ceftriaxone which is the last resort for gonorrhea treatment. Therefore, the simultaneous discovery and development of a new compound to fight this pathogen is urgently required. In this study, 8-hydroxyquinoline (8HQ) and derivatives were evaluated for their antimicrobial activities against the gonococcal pathogen using spectinomycin as the reference drug. The results showed that 8HQ derivatives gave an excellent antimicrobial potency. Particularly, the dihalogenated 8HQ (iodoquinol, clioquinol and 5,7-diCl-8HQ) exerted the high activity with MIC range of 0.08-0.15 μM, 0.10-0.20 μM and 0.28-0.56 µM, respectively, compared with the reference drug (MIC = 16 μg/mL or 48.14 μM). Moreover, these compounds were also shown to be non-cytotoxic/very high safety index. The findings reveal that these three compounds could be further developed as a new antimicrobial agent for fighting the gonorrheal disease.