Antifilarial efficacy in vitro of 2-tert-butyl-benzothiazole derivatives on adult Litomosoides carinii.
Six 2-tert-butyl-benzothiazole derivatives (2-tert-butyl-6-isothiocyanato-5-methyl-benzothiazole (CGP 21306); 3-[(2-tert-butyl-5-methyl-benzothiazole-6-yl)aminothiocar-bonyl thiol] propionic acid (CGP 21835); 2-tert-butyl-5-methyl-6-(N-methyl-piperazinyl-thiocarbonylamino)- benzothiazole(CGP 21833); 2-tert-butyl-5-methyl-6-(4-dimethylamino-piperid-1-yl-thiocarbo nylamino)- benzothiazole (CGP 26702); CGP 20376, the 5-methoxy analogue to CGP 21835 and CGP 20309, the 5-methoxy analogue to CGP 21833) were tested in vitro against adult Litomosoides carinii. When exposed to the drugs in protein-free medium RPMI 1640 drug concentrations of 1 nmol/ml caused complete immobilization of female worms within 4 h (CGP 21306, 21835, 20376) or 20 h (CGP 21833, 26702, 20309). Short term exposure for 1 h had similar effects with CGP 21306, 21835, 21833 and 20376. However, the levels of CGP 26702 and 20309 (both thiourea derivatives) had to be increased to 10 nmol/ml to obtain complete immobilization after short term exposure. Male parasites were more resistant to the drugs than females under these experimental conditions. When the medium was supplemented with 10% foetal calf serum (FCS) the efficacy of all compounds was reduced. The effect of the compounds during permanent and short term exposure on the release of microfilariae was determined over an incubation period of 7 days (medium RPMI 1640/10% FCS). In general only drug concentrations which affected markedly the motility of the worms within 2 days reduced significantly the number of microfilariae released by treated worms.(ABSTRACT TRUNCATED AT 250 WORDS)
Zahner
H
H
Institut für Parasitologie Justus-Liebig-Universität, Giessen Fed. Rep. of Germany.
Franz
M
M
Köhler
P
P
Striebel
H P
HP
D000818:Animals; D005260:Female; D005369:Filaricides / Q000138:chemical synthesis / Q000494:pharmacology*; D005370:Filarioidea / Q000187:drug effects*; D008297:Male; D008842:Microfilariae / Q000187:drug effects / Q000648:ultrastructure; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D010084:Oxidation-Reduction; D012737:Sex Factors; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology*
D005369:Filaricides; D013778:Tetrazolium Salts; D013844:Thiazoles