JAC Advance Access published online on July 1, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg322
© 2003 by The British Society for Antimicrobial Chemotherapy
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Brief report
1 Department of Protozoology,
Faculty of Tropical Medicine, Mahidol University, Bangkok
* Corresponding author. E-mail: tmppm{at}mahidol.ac.th.
Received 14 July 2002
; revised 11 February 2003
; accepted 6 May 2003
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 µM) as metronidazole (MIC = 0.096 µM), 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.
Keywords: Trichomonas vaginalis, AT-specific
drugs, DNA minor groove
In vitro susceptibility of Trichomonas
vaginalis to AT-specific minor groove binding drugs
2 School of Biological Sciences,
The University of Auckland, Auckland
3 Auckland Cancer Society Research Centre, Faculty
of Medical and Health Sciences, The University of Auckland, Auckland,
New Zealand
4 Department of Biochemistry, Faculty
of Science, Mahidol University, Bangkok, Thailand
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