Candidate vaginal microbicides with activity against Chlamydia trachomatis and Neisseriagonorrhoeae.

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 <50 microM towards C. trachomatis L2. Three INPs had a MIC <12.5 microM 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.

• Authors: Hencelyn Chu, Anatoly Slepenkin, Mikael Elofsson, Pia Keyser, Luis M de la Maza, Ellena M Peterson
• Journal: International journal of antimicrobial agents (Int J Antimicrob Agents) Vol. 36 Issue 2 Pg. 145-50 (Aug 2010) ISSN: 1872-7913 [Electronic] Netherlands
• PMID: 20605703 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright (c) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Chemical References

• Anti-Infective Agents
• Hydrazines
• INP 0341

Topics

• Administration, Intravaginal
• Animals
• Anti-Infective Agents (pharmacology, therapeutic use)
• Chlamydia Infections (prevention & control, transmission)
• Chlamydia trachomatis (drug effects)
• Disease Models, Animal
• Female
• Gonorrhea (prevention & control, transmission)
• HeLa Cells
• Humans
• Hydrazines (pharmacology, therapeutic use)
• Lactobacillus (drug effects)
• Mice
• Mice, Inbred C3H
• Microbial Sensitivity Tests
• Neisseria gonorrhoeae (drug effects)
• Vagina (microbiology)