The microbicidal agent C31G inhibits Chlamydia trachomatis infectivity in vitro

Abstract

Safe and effective vaginal microbicidal compounds are being sought to offer women an independent method for protection against transmission of sexually acquired pathogens. The purpose of this study was to examine the efficacy of two formulations of one such compound, C31G, against Chlamydia trachomatis serovar E alone, its host epithelial cell (HEC-1B) alone, and against chlamydiae-infected HEC-1B cells. Preexposure of isolated, purified infectious chlamydial elementary bodies (EB) to C31G, at pHs 7.2 and 5.7, for 1 h at 4 degrees C resulted in reduced infectivity of EB for HEC-1B cells. Examination of the C31G-exposed 35S-EB on sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiographs and by Western blotting revealed a C31G concentration-dependent and pH-dependent destabilization of the chlamydial envelope, resulting in the release of chlamydial lipopolysaccharide and proteins. Interestingly, when the host human genital columnar epithelial cells were infected with chlamydiae and then exposed to dilute concentrations of C31G which did not alter epithelial cell viability, chlamydial infectivity was also markedly reduced. C31G gained access to the developing chlamydial inclusion causing damage to or destruction of metabolically active reticulate bodies as well as apparent alteration of the inclusion membrane, which resulted in premature escape of chlamydial antigen to the infected epithelial surface. These studies show that the broad-spectrum antiviral and antibacterial microbicide C31G also has antichlamydial activity.

Toward a Design of Affordable, Topical Microbicides: Acylcarnitine Analogues

“…(Fig. (3)) Finally, glyminox (Savvy TM or 4), is an effective spermicide [22] and microbicide [23,24], has undergone Phase I trials. .…”

“…Even though chlamydial infections can be treated with antibiotics, many infections are undetected. In a recent study [60], 10.1% of the 1,631 participants (ages [18][19][20][21][22][23][24][25][26][27][28][29] have chlamydial infections. The authors estimate that 77% of all cases of chlamydial infection were never symptomatic and that 95% of untreated cases of chlamydial infection were untreated because they were never symptomatic (The remaining 5% of untreated cases of chlamydia were not treated because the women did not receive medical care for symptoms).…”

Non-Specific Microbicide Product Development: Then and Now

“…C31G was shown to be a potent inhibitor of HIV in vitro [24] and had an acceptable cytotoxicity profile [25]. Like N-9, C31G was also inexpensive, potentially broad spectrum [26], and contraceptive [27]. Therefore, a series of phase 1 safety studies were conducted with the final vaginal gel formulation of C31G, including male and female tolerance and acceptability trials [28,29]; a post-coital testing study [30], and a daily use dose escalation study [31].…”

Microbicides: A new hope for HIV prevention

“…The experience with N-9 led to a greater scrutiny of safety studies of microbicides before the commencement of larger clinical trials. Another candidate in this class, C31G (Savvy, Cellegy Pharmaceuticals, Quakertown, PA, USA), consisting of cetylbetaine and myristamine oxide, has shown in vitro safety and broad-spectrum activity against bacteria including Chlamydia trachomatis , and viruses HSV, and HIV3738. However, C31G failed to demonstrate efficacy and confirmed this surfactant might not be a good microbicide candidate39.…”