Antileishmanial activity of polycyclic derivatives.
33 polycyclic derivatives have been studied and tested on Leishmania donovani and L. major promastigotes. Their antileishmanial activity was assessed in vitro and an assay of their cytotoxicity was realized on human myelomonocytic cell line. The reference molecules used in the assays were amphotericin B and pentamidine. Among the compounds tested, 29 possess an antileishmanial activity; 25 of those were more active against L. donovani than amphotericin B, and nine were as effective as amphotericin B against L. major. Many synthesized derivatives were more active against L. donovani than against L. major. The cytotoxicity studies have shown that among the thirty-three derivatives tested, 12 molecules have an IC50 towards THP-1 cells about equal than that reference drugs, the 21 other derivatives are much less toxic. A 3D QSAR study was undertaken and has permitted to predict activity against L. donovani and L. major and to highlight critical area to optimize activity against the two species.
Sarciron
M E
ME
Department of Parasitology and Medical Mycology, EA3741, Claude Bernard University, Lyon, France. sarciron@univ-lyon1.fr
Terreux
R
R
Prieto
Y
Y
Cortes
M
M
Cuellar
M A
MA
Tapia
R A
RA
Domard
M
M
Walchshofer
N
N
Pétavy
A F
AF
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007891:Leishmania / Q000187:drug effects*; D010419:Pentamidine / Q000494:pharmacology*; D011083:Polycyclic Compounds / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
D000981:Antiprotozoal Agents; D011083:Polycyclic Compounds; D010419:Pentamidine; D000666:Amphotericin B