Potential anti-echinococcal activity of alkylaminoethers.
Trans 2-phenoxy cyclohexanol ethers (IA, IIA, IIIA, IVA, VA, and VIA), the cyclohexanol analog (IB) and one coumarinic compound (IC) were obtained and their activity against Echinococcus multilocularis metacestodes was studied and compared with that of trifluoperazine (TFP). All of these compounds are analogous to IA and belong to three classes. Class A comprises trans 2-phenoxycyclohexanol aminoethers whose alkylaminoether group varies; compound VIA bears one more methylene in its aminoether group than does compound IA. Class B consists of one compound exhibiting no phenoxy function. Class C comprises one coumarinic analog. In vitro assays were performed using metacestodes whose protoscoleces were attached to the germinal layer in open and in closed vesicles. Compounds IA and IIA exhibited the highest activity, but it was lower than that displayed by TFP under the same conditions. Compound IA was tested in an in vivo assay in jirds (50 mg/kg/daily beginning at 80 days p.i.); it produced results that were analogous to those obtained using TFP without inducing the neuroleptic effect associated with the latter. After 40-90 days' treatment, the percentage of diminution in the entire parasitic mass in the jirds that survived minimal treatment (71%) was about 41% as compared with that in untreated jirds. Histologic examination of the parasites in treated jirds revealed numerous dead protoscoleces and some parasitic dedifferentiated cells. This parasitic response may indicate that in alveolar echinococcosis, these drugs exhibit only a parasitostatic effect.
Duriez
T
T
Laboratory of Parasitology, Faculté de Pharmacie, Lille, France.
Depreux
P
P
Thuillier
P
P
Afchain
D
D
Marcincal
A
A
Deblock
S
S
D000588:Amines / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000923:Anticestodal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004443:Echinococcosis / Q000188:drug therapy*; D004446:Echinococcus / Q000187:drug effects*; D004987:Ethers / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005849:Gerbillinae; D008297:Male; D014268:Trifluoperazine / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use
D000588:Amines; D000923:Anticestodal Agents; D004987:Ethers; D014268:Trifluoperazine