[Microsomal monooxygenase inhibitors as promising agents for overcoming the drug resistance of the malaria parasite].

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.

• Authors: T G Pankova, T V Chekhonadskikh, T M Igonina, O D Zakharova, R I Salganik
• Journal: Voprosy meditsinskoi khimii (Vopr Med Khim) 1985 Nov-Dec Vol. 31 Issue 6 Pg. 15-8 ISSN: 0042-8809 [Print] Russia (Federation)
• Vernacular Title: Ingibitory mikrosomal'nykh monooksigenaz kak perspektivnye sredstva preodoleniia lekarstvennoĭ ustoĭchivosti u maliariĭnogo parazita.
• PMID: 3911572 (Publication Type: English Abstract, Journal Article)

Chemical References

• Antimalarials
• Phenylhydrazines
• Piperazines
• phenylhydrazine
• substance S
• Chloramphenicol
• Aryl Hydrocarbon Hydroxylases

Topics

• Animals
• Antimalarials
• Aryl Hydrocarbon Hydroxylases (antagonists & inhibitors)
• Chloramphenicol (pharmacology)
• Drug Resistance, Microbial
• Erythrocytes (parasitology)
• In Vitro Techniques
• Liver (enzymology)
• Mice
• Phenylhydrazines (pharmacology)
• Piperazines (pharmacology)
• Plasmodium berghei (drug effects, enzymology)