Synthetic and naturally occurring retinoids inhibit third- to fourth-stage larval development by Onchocerca lienalis in vitro.
A series of synthetic retinoids was screened for the ability to inhibit the third-to fourth-stage larval molt by Onchocerca lienalis in vitro. Of the 14 retinoids tested, eight gave significant inhibition of the molt at a concentration of 30.6 microM or less. Probit analysis of dose-response data collected for these active compounds indicated values for ED50 in the range of 3.7-17.1 microM. In general, the most active of these N-substituted retinamides were those with small alkyl or monohydroxy alkyl substituents. The most active of these was all-trans-N-(2-hydroxyethyl)retinamide with an ED50 of 3.7 microM. Both the all-trans and 13-cis isomers of the alkyl substituted derivatives were active, the all-trans-N-hydroxyethyl derivative being approximately 5 times as active as the corresponding 13-cis isomer. The N-2,3 dihydroxypropyl derivative, two derivatives with aromatic side chains and three N-(retinoyl)amino acids were inactive by the criteria set in the initial screening. There was no strict correlation between growth regulating activity against O. lienalis and binding affinity for a retinol binding protein from Onchocerca gibsoni.
Lok
J B
JB
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia.
Morris
R A
RA
Sani
B P
BP
Shealy
Y F
YF
Donnelly
J J
JJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D008024:Ligands; D009854:Onchocerca / Q000187:drug effects* / Q000254:growth & development; D012176:Retinoids / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D012177:Retinol-Binding Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology; D014801:Vitamin A / Q000378:metabolism / Q000494:pharmacology
D008024:Ligands; D012176:Retinoids; D012177:Retinol-Binding Proteins; D014801:Vitamin A; D014212:Tretinoin