Antifilarial activities of benzazole derivatives. 2. Microfilaricidal effects against Litomosoides carinii, Acanthocheilonema. vitae, Brugia malayi and B. pahangi in Mastomys natalensis.
The spectrum of antimicrofilarial activities of eighteen 2-tertbutylbenzazole derivatives was evaluated comparatively in Mastomys natalensis infected with Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi or B. pahangi. The minimal effective dose (DEM) against microfilariae (greater than 95% reduction of microfilariae counts in the peripheral blood) was determined on day 3 (DEM-3), on day 7, 14, 21, 28 and 42 (DEM-7, DEM-14, DEM-21, DEM-28 and DEM-42) after the first treatment. All compounds were effective against the microfilariae of all 4 species. The benzoxazole derivatives were invariably less potent than the corresponding benzothiazole analogues. Upon repeated oral treatment (once daily [o.d.] for five days) the DEM-7 of the benzoxazoles varied depending on the species and on the chemical structure between 25 mg/kg o.d. x 5 and greater than 100mg/kg o.d. x 5 days. Within the benzothiazole series the DEM-7 varied between 6.25 mg/kg o.d. x 5 and 100 mg/kg x 5. In all but 5 of the 40 parasite-compound combinations of the benzothiazoles the 5-methoxy-derivates were more effective than the 5-methyl analogues. Similar differences were found with the eight benz-oxazoles tested. The lowest DEM-7 was observed with compound CGP 20308 which is 2-tert-butyl-5-methoxy-6-isothio-cyanatobenzothiazole and with compound CGP 20376 which is 3-(2-tert-butyl-5-methoxy-benzothiazol-6-yl] amino-thiocabo-nylthio) propionic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
Zahner
H
H
Institute for Parasitology, Justus Liebig University Giessen, FRG.
Striebel
H P
HP
Schütze
H R
HR
Sänger
I
I
Müller
H A
HA
Schultheiss
K
K
D000284:Administration, Oral; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D001583:Benzoxazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002009:Brugia / Q000187:drug effects; D004153:Dipetalonema / Q000187:drug effects; D004154:Dipetalonema Infections / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004605:Elephantiasis, Filarial / Q000188:drug therapy*; D005368:Filariasis / Q000188:drug therapy*; D005369:Filaricides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005370:Filarioidea / Q000187:drug effects; D007279:Injections, Subcutaneous; D008842:Microfilariae / Q000187:drug effects; D009115:Muridae
D000871:Anthelmintics; D001583:Benzoxazoles; D005369:Filaricides