HYBRID MOLECULES - GROWTH-INHIBITION OF LEISHMANIA-DONOVANI PROMASTIGOTES BY THIOSEMICARBAZONES OF 3-CARBOXY-BETA-CARBOLINES
HYBRID MOLECULES - GROWTH-INHIBITION OF LEISHMANIA-DONOVANI PROMASTIGOTES BY THIOSEMICARBAZONES OF 3-CARBOXY-BETA-CARBOLINES
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DOI：
10.1021/jm00126a021
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发表时间：
1989-06-01
影响因子：
7.3
通讯作者：
POTIER, P
中科院分区：
文献类型：
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作者：
DODD, RH;OUANNES, C;POTIER, P
化合物2和化合物3的缩氨基硫脲对杜氏利什曼原虫前鞭毛体的体外生长有明显的抑制作用，当浓度分别为5.0和2.5µm时，抑制率为50%，而化合物2和17.5µm时则为不可逆抑制。吡啶-2-甲醛缩氨基硫脲(化合物4)的活性较低，而β-甲酸甲酯-3-甲酸甲酯(化合物1)和5-甲酰基-6-氮杂环己烷-2-羧酸乙酯(化合物5)的缩氨基硫脲(化合物5)在测试的最高浓度下都没有活性。在引起前鞭毛体生长抑制约50%的浓度下，观察到化合物2优先阻止DNA而不是RNA合成，但对于化合物3，情况正好相反。化合物3是被研究的最活跃的类似物，因此可能至少部分地通过一种新的机制发挥作用，尽管目前尚不清楚。
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 .mu.M, respectively, while irreversible growth inhibition was achieved at 40 (compound 2) and 17.5 .mu.M (compound 3). The thiosemicarbazone of pyridine-2-carboxaldehyde (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 partly, via a novel, though as yet unelucidated, mechanism.