Anti-Leishmanial and Cytotoxic Activities of a Series of Maleimides: Synthesis, Biological Evaluation and Structure-Activity Relationship

作者：Fan, Yongxian; Lu, Yuele; Chen, Xiaolong^*; Tekwani, Babu; Li, Xing-Cong; Shen, Yinchu

来源：Molecules, 2018, 23(11): 2878.

DOI：10.3390/molecules23112878

• anti-leishmanial activity
• Leishmania donovani
• maleimides
• cytotoxicity
• SAR

In the present study, 45 maleimides have been synthesized and evaluated for anti-leishmanial activities against L. donovani in vitro and cytotoxicity toward THP1 cells. All compounds exhibited obvious anti-leishmanial activities. Among the tested compounds, there were 10 maleimides with superior anti-leishmanial activities to standard drug amphotericin B, and 32 maleimides with superior anti-leishmanial activities to standard drug pentamidine, especially compounds 16 (IC50 < 0.0128 mu g/mL) and 42 (IC50 < 0.0128 mu g/mL), which showed extraordinary efficacy in an in vitro test and low cytotoxicities (CC50 > 10 mu g/mL). The anti-leishmanial activities of 16 and 42 were 10 times better than that of amphotericin B. The structure and activity relationship (SAR) studies revealed that 3,4-non-substituted maleimides displayed the strongest anti-leishmanial activities compared to those for 3-methyl-maleimides and 3,4-dichloro-maleimides. 3,4-dichloro-maleimides were the least cytotoxic compared to 3-methyl-maleimides and 3,4-non-substituted maleimides. The results show that several of the reported compounds are promising leads for potential anti-leishmanial drug development.

• 出版日期2018-11
• 单位浙江工业大学