Antifilarial and trypanocidal properties of phenothiazines and related polycyclics as new lead structures.
New phenothiazine derivatives and 4 related lead structures have been studied for their antifilarial and trypanocidal properties. Regarding phenothiazine derivatives, the nitrile group at the 3 position on the phenothiazine ring had a strong in vitro antifilarial effect against Molinema dessetae infective larvae. Among the 4 new lead structures, compound 4 or naphtho(2',3': 4,5) thiazolo(3,2-a)benzimidazole-7,12-dione was the most antifilarial, with IC50 of 8 microM at day 8. These results justify further studies in vivo. A slight effect was observed against the trypanosomes maintained in vitro since minimum inhibitory concentrations of active compounds were 50 microM after a 24-h incubation period. Nevertheless, no trypanocidal activity was observed in vivo after a 100 mg kg-1 treatment and the compound 3 or dibenzo(b,f)(1,4)thiazine-11-amine was lethal at this dose. These new lead structures have now to be optimised using pharmaco-modulations.
Loiseau
P M
PM
Biologie et Contrôle des Organismes Parasites, Université de Paris-Sud, Châtenay-Malabry, France.
Mettey
Y
Y
Vierfond
J M
JM
D000818:Animals; D005369:Filaricides / Q000737:chemistry / Q000494:pharmacology*; D005370:Filarioidea / Q000187:drug effects*; D007814:Larva / Q000187:drug effects; D010640:Phenothiazines / Q000737:chemistry / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
D005369:Filaricides; D010640:Phenothiazines; D014344:Trypanocidal Agents