Abstract

A series of coumarin-based trisubstituted methanes (TRSMs) having uracil scaffold was synthesised employing a green, chromatography-free, and a highly efficient sonochemical multicomponent reaction of diverse aldehydes with 1,3-dimethyl-6-aminouracil and 4-hydroxy-coumarin in the presence of a catalytic amount of DABCO at room temperature and tested their anthelmintic efficacy against helminth parasites, Raillietina echinobothrida and Syphacia obvelata. Some of the TRSMs with substituents in the para position of the phenyl ring showed excellent anthelmintic activity in comparison to the commonly used drugs such as albendazole and praziquantel. The docking study revealed the binding interaction of all the optimized compounds with several amino acid residues in the active site of β-tubulin. The compounds showing good docking score with β-tubulin showed comparable anthelmintic activity experimentally as well.

Graphic Abstract

A series of coumarin based trisubstituted methanes (TRSMs) were synthesized and they showed excellent anthelmintic properties in comparison to conventional benzimidazoles.

中文翻译：

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香豆素基三取代甲烷作为强驱虫药：合成，分子对接和体外功效

摘要

合成了一系列具有尿嘧啶支架的基于香豆素的三取代甲烷（TRSM），该方法采用了绿色，无色谱且各种醛与1,3-二甲基-6-氨基尿嘧啶和4-羟基香豆素的高效声化学多组分反应。在室温下有催化量的DABCO存在下，并测试了它们对蠕虫寄生虫，棘轮Rail棘突线虫和Syphacia obvelata的驱虫功效。与苯丙唑和吡喹酮等常用药物相比，某些在苯环对位带有取代基的TRSM表现出优异的驱虫活性。对接研究表明，所有优化的化合物都与在活性位点上的几个氨基酸残基发生结合相互作用。β-微管蛋白。表现出与β-微管蛋白良好对接分数的化合物在实验上也显示出相当的驱虫活性。

图形摘要

合成了一系列基于香豆素的三取代甲烷（TRSM），与传统的苯并咪唑相比，它们显示出优异的驱虫性能。