Synthesis and antileishmanial activity of 6-mono-substituted and 3,6-di-substituted acridines obtained by acylation of proflavine.
Two new series of diaminoacridinic derivatives obtained from proflavine and N-(6-amino-3-acridinyl)acetamide were synthesised and assessed for their cytotoxic and antileishmanial activities. Two compounds, N-[6-(acetylamino)-3-acridinyl]acetamide and N-[6-(benzoylamino)-3-acridinyl]benzamide demonstrated highly specific antileishmanial properties against the intracellular amastigote form of the parasite. Structure-activity relationships established that the antiproliferative activity against human cells was greatly enhanced by the presence of a benzoylamino group in 6-mono-substituted acridines, while the presence of two acetylamino or benzoylamino groups in 3,6-di-substituted acridines strongly increased the specificity of the molecules for Leishmania parasite, suggesting that symmetric conformations could preferentially interfere with Leishmania metabolism.
Di Giorgio
Carole
C
Laboratoire de Parasitologie, Hygiene et Zoologie, Faculté de Pharmacie, 27 Bd. Jean Moulin, 13385 Marseille Cedex 05, France. Carole.Digiorgio@Pharmacie.univ-mrs.fr
Shimi
Kamal
K
Boyer
Gérard
G
Delmas
Florence
F
Galy
Jean-Pierre
JP
D000166:Acridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D000215:Acylation; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D018314:Leishmania infantum / Q000187:drug effects*; D015394:Molecular Structure; D011370:Proflavine / Q000737:chemistry*
D000166:Acridines; D000981:Antiprotozoal Agents; D011370:Proflavine