Hybrid molecules: growth inhibition of Leishmania donovani promastigotes by thiosemicarbazones of 3-carboxy-beta-carbolines.
The thiosemicarbazones of beta-carboline-3-carboxaldehyde (compound 2) and 3-acetyl-beta-carboline (compound 3) were found to effectively inhibit the in vitro growth of the promastigote form of Leishmania donovani, 50% inhibition being obtained at concentrations of 5.0 and 2.5 microM, respectively, while irreversible growth inhibition was achieved at 40 (compound 2) and 17.5 microM (compound 3). The thiosemicarbazone of pyridine-2-carboxyaldehyde (compound 4) was considerably less active while both methyl beta-carboline-3-carboxylate (compound 1) and the thiosemicarbazone of ethyl 5-formyl-6-azaindole-2-carboxylate (compound 5) were inactive at the highest concentrations tested. At concentrations provoking approximately 50% growth inhibition of promastigotes, compound 2 was observed to preferentially block DNA rather than RNA synthesis, but for compound 3, the reverse was true. Compound 3, the most active analogue studied, may thus act, at least partially, via a novel, though as yet unelucidated, mechanism.
Dodd
R H
RH
Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
Ouannès
C
C
Robert-Gèro
M
M
Potier
P
P
D000818:Animals; D002243:Carbolines / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000096:biosynthesis; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity
D002243:Carbolines; D013882:Thiosemicarbazones; C059954:3-acetyl-beta-carboline thiosemicarbazone; D012313:RNA; D004247:DNA