Publication: Interactions between antiplasmodial 3,6-diamino-1′-dimethyl-9- anilinoacridine and hematin and concanamycin A
Issued Date
2007-11-01
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ISSN
01251562
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2-s2.0-37849020756
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Mahidol University
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SCOPUS
Bibliographic Citation
Southeast Asian Journal of Tropical Medicine and Public Health. Vol.38, No.6 (2007), 979-982
Suggested Citation
Saranya Auparakkitanon, Kritchai Poonchareon, Kittipat Sopitthummakhun, Prapon Wilairat Interactions between antiplasmodial 3,6-diamino-1′-dimethyl-9- anilinoacridine and hematin and concanamycin A. Southeast Asian Journal of Tropical Medicine and Public Health. Vol.38, No.6 (2007), 979-982. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/24691
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Title
Interactions between antiplasmodial 3,6-diamino-1′-dimethyl-9- anilinoacridine and hematin and concanamycin A
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Abstract
Antiplasmodial 9-anilinoacridine derivatives exert their effects either by inhibiting DNA topoisomerase (topo) II or by interfering with heme crystallization within the parasite acidic food vacuole. Previous studies have shown that analogs of 9-anilinoacridine containing 3,6-diamino substitutions (in the acridine ring) inhibit Plasmodium falciparum DNA topo II in situ, whereas those with a 3,6-diCl substitution act by inhibiting beta-hematin formation, a property also seen with 3,6-diamino-1′-dimethyl-9-anilinoacridine (DDAA). To understand this seemingly anomalous property of DDAA, studies of its interaction with hematin and localization within the parasite food vacuole were undertaken. A weak interaction with hematin was demonstrated spectroscopically. Antagonism of DDAA inhibition of Plasmodium falciparum growth in culture by concanamycin A, a macrolide antibiotic inhibitor of vacuolar H +-ATPase derived from Streptomyces sp, was equivocal.