文章基本信息

标题：Antimalarial Quinones for Prophylaxis Based on a Rationale of Inhibition of Electron Transfer in Plasmodium
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作者：Yieh-Ping Wan ; Thomas H. Porter ; Karl Folkers 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1974
卷号：71
期号：3
页码：952-956
DOI：10.1073/pnas.71.3.952
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Knowledge of the biochemistry of Plasmodium is emerging as a new field. Previous studies showed that the parasite apparently requires electron transfer for energy, and techniques to study such energy mechanisms are available. The discovery of the existence of coenzyme Q8 in Plasmodium implies an indispensable functionality for this redox entity in the electron transfer of the parasite, as coenzyme Qn similarily functions in other forms of life. Effective antimalarial activity in prophylaxis has been demonstrated in sporozoite-induced infections by Plasmodium gallinaceum in chicks by several representatives of 7-alkylmercapto-6-hydroxy-5,8-quinolinequinones. The absence of toxicity in this assay even at greatly elevated dosage underscores the achievement of selectivity and safety to the host for the potential utilization of antimetabolites of coenzyme Qn as medicinals. Seven new 7-alkylmercapto-6-hydroxy-5,8-quinoline-quinones were synthesized. The structural variations of the 7-alkylmercapto group in relationship to the antimalarial activities reveal substantial differences in biological activities, which can reflect molecular specificities of enzyme sites and which are not evident from the deceptively minor structural differences in the alkylmercapto groups. These analogs of coenzyme Q8 having effective antimalarial activity are known to inhibit mammalian coenzyme Qn enzymes, and could be useful in elucidation of the basic electron transfer mechanisms of Plasmodium.
关键词：coenzyme Q ; malaria ; antimetabolites ; therapy ; bioenergetics