Antifilarial activities of benzazole derivatives. 1. Macrofilaricidal effects against Litomosoides carinii, Dipetalonema viteae, Brugia malayi, and B. pahangi in Mastomys natalensis.

Eighteen 2-tert-butyl-benzazole derivatives were evaluated comparatively as macrofilaricidal agents against L. carinii (L.c.), D. viteae (D.v.), B. malayi (B.m.) and B. pahangi (B.p.). Upon repeated treatment (once daily) for five consecutive days the eight benzoxazole derivatives were invariably less potent than the corresponding benzothiazole derivatives. The minimal curative dose (DCM) of the benzoxazoles varied depending on the species and on the chemical structure between 25 and 100 mg/kg p.o. once daily for five days. In the benzothiazole series the lowest DCMs were observed with compound CGP 20376 which is the 5-methoxy-6-dithiocarbamic-S-(2-carboxy-ethyl)ester derivative. This compound eliminated all macrofilariae of L.c., B.m. and Bp. at 6.25 mg/kg p.o. once a day for five days, whereas 12.5 mg/kg x 5 days were needed against D.v. For all other benzothiazole derivatives the DCMs varied between 6.25 mg/kg p.o. x 5 to 100 mg/kg x 5. Six of the most potent benzothiazoles were tested by single oral treatment. In general doses had to be increased 2-4 times to reach minimum curative effects. CGP 20376 was fully effective against B.m. and B.p. at 12.5 mg/kg p.o., against L.c. at 25 mg/kg p.o. and against D.v. at 50 mg/kg p.o.. This compound has been selected from this series of novel benzazoles as a first candidate for trials against human bancroftian filariasis.