In vitro antifilarial evaluation of phenoxycyclohexane derivatives.
Numerous potential inhibitors of the phosphoenolpyruvate-carboxylase found in Molinema dessetae were synthesized and evaluated as inhibitors of the purified enzyme and as killers, in vitro, of M. dessetae adult females and infective larvae. Phosphoenolpyruvate analogs (or derivatives) appeared disappointing whereas phenoxycyclohexane derivatives inhibited the enzyme in a non-competitive manner and killed the parasites. The compounds P2281 and P2285, for example, had Ki values of 122 and 93 microM, respectively. In vivo tests of the most effective phenoxycyclohexanes will now be carried out to check their potential as antifilarial drugs.
Loiseau
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PM
Biologie et Contrôle des Organismes Parasites, Université de Paris-Sud, Châtenay-Malabry, France.
Depreux
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D000818:Animals; D003510:Cyclohexanes / Q000494:pharmacology*; D004153:Dipetalonema / Q000187:drug effects* / Q000201:enzymology; D005260:Female; D005368:Filariasis / Q000188:drug therapy; D005369:Filaricides / Q000494:pharmacology*; D008297:Male; D010730:Phosphoenolpyruvate Carboxylase / Q000037:antagonists & inhibitors*; D012377:Rodentia / Q000469:parasitology
D003510:Cyclohexanes; D005369:Filaricides; D010730:Phosphoenolpyruvate Carboxylase