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  • Title: [Microsomal monooxygenase inhibitors as promising agents for overcoming the drug resistance of the malaria parasite].
    Author: Pankova TG, Chekhonadskikh TV, Igonina TM, Zakharova OD, Salganik RI.
    Journal: Vopr Med Khim; 1985; 31(6):15-8. PubMed ID: 3911572.
    Abstract:
    A relationship was found between resistance of malarial plasmodium to chloroquine and the increased activity of microsomal monooxygenases, metabolizing drugs in the parasite. A search for effective inhibitors of the enzymatic system was initiated. For this purpose inhibitory effects of 17 alpha-hydrodeoxycorticosterone (substance S), 21-acetate-17 alpha-hydroxydeoxycorticosterone (acetate of substance S), 4-bromomethyl-2,2,5,5-tetramethyl-3-imidazoline-3-oxide-1-oxyl (RBr), Cu(lysine)2 on activity of arylhydroxycarbone hydroxylase were studied using mice liver microsomes and homogenate of mice malaria cells Plasmodium berghei. Cu(lysine)2 and phenylhydrazine were found to be the most effective inhibitors of the enzyme in samples containing mice liver microsomes or malarial parasite. The data obtained suggest that the inhibitors of microsomal monooxygenases may serve as means for a decrease in malarial parasite resistance to chloroquine.
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