Candidate vaginal microbicides with activity against Chlamydia trachomatis and Neisseria gonorrhoeae

Chu, Hencelyn; Slepenkin, Anatoly; Elofsson, Mikael; Keyser, Pia; de la Maza, Luis M.; Peterson, Ellena M.

doi:10.1016/j.ijantimicag.2010.03.018

« Previous Next »International Journal of Antimicrobial Agents
Volume 36, Issue 2 , Pages 145-150, August 2010

Candidate vaginal microbicides with activity against Chlamydia trachomatis and Neisseria gonorrhoeae

Hencelyn Chu
- Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA
Anatoly Slepenkin
- Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA
Mikael Elofsson
- Department of Chemistry, Umeå University, Sweden
Pia Keyser
- Creative Antibiotics Sweden AB, Umeå, Sweden
Luis M. de la Maza
- Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA
Ellena M. Peterson
- Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA
- Corresponding author. Present address: Department of Pathology and Laboratory Medicine, Medical Science Building, Room D-440, University of California–Irvine, Irvine, CA 92697-4800, USA. Tel.: +1 949 824 4169; fax: +1 949 824 2160.

Received 5 December 2009; accepted 9 March 2010. published online 02 June 2010.

Abstract

Vaginal microbicides with activity towards organisms that cause sexually transmitted infections have been proposed as a strategy to reduce transmission. Small-molecule inhibitors of Chlamydia trachomatis serovar D belonging to the class of salicylidene acylhydrazides (INPs) have been shown to work through a mechanism that involves iron restriction. Expanding on this work, ten INPs were tested against a lymphogranuloma venereum strain of C. trachomatis (serovar L2), Neisseria gonorrhoeae, and hydrogen peroxide-producing Lactobacillus crispatus and Lactobacillus jensenii. Seven INPs had minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations of <50μM towards C. trachomatis L2. Three INPs had a MIC <12.5μM against N. gonorrhoeae. Inhibition was reversed by iron, holo-transferrin and holo-lactoferrin but not by the iron-poor forms of these compounds. The compounds exhibited no bactericidal activity toward Lactobacillus. The INPs were not cytotoxic to HeLa 229 cells. When INP 0341 was tested in a mouse model of a Chlamydia vaginal infection there was a significant reduction in the number of mice shedding C. trachomatis up to 4 days after infection (P<0.01). In summary, select INPs are promising vaginal microbicide candidates as they inhibit the growth of two common sexually transmitted organisms in vitro, are active in a mouse model against C. trachomatis, are not cytotoxic and do not inhibit organisms that compose the normal vaginal flora.