ABSTRACT
Vaginal trichomoniasis is a highly prevalent sexually transmitted disease caused by a microaerophilic protozoan Trichomonas vaginalis. The disease is one of the most common sexually transmitted disease and can augment the predisposition of individuals to human immunodeficiency virus (HIV) infection. Although the disease can be treated with metronidazole and related 5-nitroimidazole, cases of trichomonal vaginitis which are refractory to standard treatment seems to be increasing. Clearly, new antitrichomonad agents are needed and DNA topoisomerase II may acts as a new target for antitrichomonad agents. In this study, in vitro sensitivity of T. vaginalis to DNA topoisomerase II was investigated. Axenic culture of local strain of T. vaginalis was performed. Both eukaryotic and prokaryotic DNA topoisomerase II inhibitors such as ellipticine, amsacrine and fluoroquinolones were tested for effectiveness against T. vaginalis in vitro compared to metronidazole. T. vaginalis was sensitive to metronidazole under aerobic conditions. Minimal inhibitory concentrations (MICs) of eukaryotic DNA topoisomerase II inhibitors, ellipticine and amsacrine, were 6.4 mM and 64 mM, respectively. The MICs of prokaryotic DNA topoisomerase II or DNA gyrase inhibitors; ciprofloxacin, ofloxacin and norfloxacin were 64, 960 and 1,280 mM, respectively. Based on the results, among DNA topoisomerase II inhibitors ellipticine was the most effective drug against T. vaginalis in vitro whereas fluoroquinolones did not show high antitrichomonad activity.
Subject(s)
Amsacrine/pharmacology , Animals , Anti-Infective Agents/pharmacology , Antitrichomonal Agents/pharmacology , DNA Topoisomerases, Type II/antagonists & inhibitors , Ellipticines/pharmacology , Enzyme Inhibitors/pharmacology , Fluoroquinolones , Metronidazole/pharmacology , Parasitic Sensitivity Tests , Trichomonas vaginalis/drug effectsABSTRACT
Cultured Chinese hamster ovary (CHO) cells were pre-treated with m-AMSA (amsacrine) and post-treated with different doses of polycationic compound poly-D-lysine (PDL) during G2 period in order to test on the frequency of chromatid-type aberrations. The present results indicate that PDL enhances the genotoxic action of m-AMSA measured as induced chromatid aberrations.