Brugia malayi and Acanthocheilonema viteae: antifilarial activity of transglutaminase inhibitors in vitro.
The possible involvement of transglutaminase-catalyzed reactions in survival of adult worms, microfilariae (mf), and infective larvae of the filarial parasite Brugia malayi was studied in vitro by using the specific pseudosubstrate monodansylcadaverine (MDC) and the active-site inhibitors cystamine or iodoacetamide. These inhibitors significantly inhibited parasite mobility in a dose-dependent manner. This inhibition was associated with irreversible biochemical lesions followed by filarial death. A structurally related, inactive analog of MDC, dimethyldansylcadaverine, did not affect the mobility or survival of the parasites. Adult worms failed to release mf when they were incubated in the presence of MDC or cystamine, and this inhibitory effect on mf release was concentration dependent. Similar embryostatic and macrofilaricidal effects of MDC were observed in Acanthocheilonema viteae adult worms. These studies suggest that transglutaminase-catalyzed reactions may play an important role in the growth, development, and survival of filarial parasites.
Rao
U R
UR
College of Public Health, University of South Florida, Tampa 33612.
Mehta
K
K
Subrahmanyam
D
D
Vickery
A C
AC
D000818:Animals; D002009:Brugia / Q000187:drug effects*; D002103:Cadaverine / Q000031:analogs & derivatives / Q000494:pharmacology; D003538:Cystamine / Q000494:pharmacology; D004153:Dipetalonema / Q000187:drug effects*; D005260:Female; D005369:Filaricides / Q000494:pharmacology*; D007460:Iodoacetamide / Q000494:pharmacology; D008297:Male; D010084:Oxidation-Reduction; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D011503:Transglutaminases / Q000037:antagonists & inhibitors*
D005369:Filaricides; D013778:Tetrazolium Salts; D013844:Thiazoles; C073673:dimethyldansylcadaverine; D011503:Transglutaminases; C022616:thiazolyl blue; C008542:monodansylcadaverine; D002103:Cadaverine; D003538:Cystamine; D007460:Iodoacetamide