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Inhibitory effects of 9-anilinoacridines on Plasmodium falciparum gametocytes

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Abstract:

Summary

Two gametocyte-producing isolates of Plasmodium falciparum, KT1 and KT3, were cultivated in vitro. On day 11 of cultivation, pure gametocytes containing stage II, III and IV were used to test the gametocytocidal activity of 9-anilinoacridines that had previously demonstrated their activity against the asexual stage of the parasite. After drug exposure for 48 h, gametocytes were maintained without drugs for another 2 days before thin films were prepared for parasite counting. Gametocytocidal activities of 13 analogs of 9-anilinoacridine were observed with 50% inhibitory concentrations in the range of 0.6 μmto > 100 μm. The most active compound was 1′-CH2NMe2-9-anilinoacridine. Anilinoacridine derivatives with 3,6-diamino substitution had reduced gametocytocidal activity in contrast to their enhancing effect against the asexual forms. Morphological abnormalities of gametocytes were observed following drug exposure.

Keywords: 9-anilinoacridines; Plasmodium falciparum; gametocytes

Document Type: Research Article

DOI: http://dx.doi.org/10.1046/j.1365-3156.2001.00656.x

Affiliations: 1: Department of Protozoology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand 2: Cancer Research and Developmental Biology, University of Auckland Medical School, Auckland, New Zealand 3: Cancer Research Laboratory, University of Auckland Medical School, Auckland, New Zealand 4: Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok,Thailand

Publication date: January 1, 2001

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