Several indolo[2,1-b]quinazoline-6,12-dione (tryptanthrin) derivatives exhibited remarkable activity at concentrations below 100 ng/mL when tested against in vitro Leishmania donovani amastigotes. The in vitro toxicity studies indicate that the compounds are fairly well tolerated in both macrophage and neuronal lines. An analysis based on qualitative and quantitative structure-activity relationship studies between in vitro antileishmanial activity and molecular electronic structure of 27 analogues of indolo[2,1-b]quinazoline-6,12-dione is presented here by using a combination of semi-empirical AM1 quantum chemical, cyclic voltammetry and a pharmacophore generation (CATALYST) methods. A modest to good correlation is observed between activity and a few calculated molecular properties such as molecular density, octanol-water partition coefficient, molecular orbital energies, and redox potentials. Electron transfer seems to be a plausible path in the mechanism of action of the compounds. A pharmacophore generated by using the 3-D QSAR of CATALYST produced a fairly accurate predictive model of antileishmanial activity of the tryptanthrins. The validity of the pharmacophore model extends to structurally different class of compounds that could open new frontiers for study. The carbonyl group of the five- and six-membered rings in the indolo[2,1-b]quinazoline-6,12-dione skeleton and the electron transfer ability to the carbonyl atom appear to be crucial for activity.

中文翻译：

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使用量子化学，循环伏安法和3-D-QSAR CATALYST方法分析合成吲哚[2,1-b]喹唑啉-6,12-二酮衍生物的立体电子性质，作用机理和药效团与抗霉菌活性的关系。

当针对体外利什曼原虫donovani amastigotes进行测试时，几种吲哚[2,1-b]喹唑啉-6,12-二酮（色胺酮）衍生物在低于100 ng / mL的浓度下表现出显着活性。体外毒性研究表明，该化合物在巨噬细胞和神经元细胞系中均具有良好的耐受性。本文通过结合定性和定量构效关系研究，对吲哚[2,1-b]喹唑啉-6,12-二酮的27种类似物的体外抗衰老活性和分子电子结构进行了分析。经验AM1量子化学，循环伏安法和药效基团生成（CATALYST）方法。在活性与一些计算出的分子特性（例如分子密度，辛醇-水分配系数，分子轨道能量和氧化还原电位。电子转移似乎是化合物作用机理的合理途径。通过使用CATALYST的3-D QSAR生成的药效基团产生了一个相当准确的色胺酮抗虫活性的预测模型。药效团模型的有效性扩展到结构上不同的化合物类别，这些化合物可能会为研究打开新的领域。吲哚并[2,1-b]喹唑啉-6,12-二酮骨架中五元环和六元环的羰基和向羰基原子的电子转移能力对于活性至关重要。通过使用CATALYST的3-D QSAR生成的药效基团产生了一个相当准确的色胺酮抗虫活性的预测模型。药效团模型的有效性扩展到结构上不同的化合物类别，这些化合物可能会为研究打开新的领域。吲哚并[2,1-b]喹唑啉-6,12-二酮骨架中五元环和六元环的羰基和向羰基原子的电子转移能力对于活性至关重要。通过使用CATALYST的3-D QSAR生成的药效基团产生了一个相当准确的色胺酮抗虫活性的预测模型。药效团模型的有效性扩展到结构上不同的化合物类别，这些化合物可能会为研究打开新的领域。吲哚并[2,1-b]喹唑啉-6,12-二酮骨架中五元环和六元环的羰基和向羰基原子的电子转移能力对于活性至关重要。