In vitro effects of 2-tert-butyl-benzothiazole derivatives on microfilariae of Litomosoides carinii, Brugia malayi and Acanthocheilonema viteae.
Six 2-tert-butyl-benzothiazole derivatives (2-tert-butyl-6-iso-thiocyanato-5-methyl-benzothiazole CGP 21306); 3-[(2-tert-butyl-5-methyl-benzothiazole-6-yl) aminothiocarbonylthiol] propionic acid (CGP 21835); 2-tert-butyl-5-methyl-6-(N-methyl-piperazinyl-thiocarbonylamino)-b enzothiazole (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) with known, high filaricidal activity in vivo were tested for in vitro efficacy against microfilariae of L. carinii (Lc), B. malayi (Bm) and A. viteae (Av) in order to study intrinsic antifilarial activities. All drugs affected the motility of the microfilariae of the three species in a species, dose and time dependent fashion. Lc was the most sensitive, Av the most resistant species. CGP 20376 and 21835 were the most effective compounds followed by CGP 21306. Complete immobilization of microfilariae was observed after 20 h in protein-free medium RPMI 1640 at drug concentrations of 0.1 to 10 nmol/ml. Effects were still marked 2 when graded on a 4 (full motility) to 0 (immobile) scale at concentrations of 0.01-0.1 nmol/ml. In the case of the thiourea derivatives CGP 21833, 26702 and 20309 concentrations had to be increased 10-100 fold to obtain similar effects. When proteins were present in the incubation medium (10% foetal calf serum, 100% normal serum) the efficacy of the compounds was reduced, i.e. drug concentrations had to be increased up to 100 fold to produce similar effects as in protein-free medium.(ABSTRACT TRUNCATED AT 250 WORDS)
Zahner
H
H
Institut für Parasitologie der Justus-Liebig-Universität Giessen, Fed. Rep. of Germany.
Johri
G N
GN
Köhler
P
P
Striebel
H P
HP
Franz
M
M
D000818:Animals; D002009:Brugia / Q000187:drug effects*; D004153:Dipetalonema / Q000187:drug effects*; D005369:Filaricides / Q000494:pharmacology*; D005370:Filarioidea / Q000187:drug effects*; D007814:Larva; D008842:Microfilariae / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009115:Muridae / Q000469:parasitology*; D013844:Thiazoles / Q000494:pharmacology*
D005369:Filaricides; D013844:Thiazoles