title: In vitro susceptibility of Trichomonas vaginalis to AT-specific minor groove binding drugs.
abstract: Trichomoniasis is one of the most common sexually transmitted diseases, with around 120 million world-wide suffering from Trichomonas vaginalis-induced vaginitis every year. Although trichomoniasis can be treated with metronidazole, the prevalence of metronidazole-resistant T. vaginalis seems to be increasing. Since the percentage of AT base pairs in T. vaginalis DNA (71%) is very much higher than in human cells, in this study a series of bisquaternary quinolinium salt compounds with high AT-binding specificity were tested for their antitrichomonal activities. Minimum inhibitory concentrations (MICs) were determined for these compounds against a local strain of T. vaginalis in culture. Among 14 bisquaternary quinolinium compounds tested, an N-ethyl derivative was the most effective drug against T. vaginalis, being nearly as potent (MIC = 0.16 microM) as metronidazole (MIC = 0.096 microM), and with low toxicity towards human cells. The nature of the substitution at the quinolinium quaternary centre appears to be important in terms of effectiveness of bisquaternary compounds against the parasite. In contrast, no clear relationships could be seen for substituents on the quinolinium ring; Me and Cl substituted analogues showed higher activity against trichomonads, whereas OMe, NHMe and NH2 substituents decreased activity.
authors.affiliation: Department of Protozoology, Faculty of Tropical Medicine, Mahidol University, Bangkok. tmppm@mahidol.ac.th
authors.forename: Porntip
authors.initials: P
authors.lastname: Chavalitshewinkoon-Petmitr
authors.forename: Muhaimin
authors.initials: M
authors.lastname: Ramdja
authors.forename: Somsri
authors.initials: S
authors.lastname: Kajorndechakiat
authors.forename: Raymond K
authors.initials: RK
authors.lastname: Ralph
authors.forename: William A
authors.initials: WA
authors.lastname: Denny
authors.forename: Prapon
authors.initials: P
authors.lastname: Wilairat
mesh_terms: D000818:Animals; D020029:Base Pairing / Q000187:drug effects* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004351:Drug Resistance / Q000502:physiology*; D006801:Humans; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011806:Quinolinium Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014246:Trichomonas vaginalis / Q000187:drug effects* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D011806:Quinolinium Compounds