一系列马来酰亚胺的抗利什曼原虫和细胞毒性活性：合成、生物评价和构效关系。
Anti-Leishmanial and Cytotoxic Activities of a Series of Maleimides: Synthesis, Biological Evaluation and Structure-Activity Relationship.
机构信息
Institute of Fermentation Engineering, College of Biotechnology and Bioengineering, Zhejiang University of Technology, 18# Chaowang Road, Hangzhou 310032, China.
National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences and Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
出版信息
Molecules. 2018 Nov 5;23(11):2878. doi: 10.3390/molecules23112878.
In the present study, 45 maleimides have been synthesized and evaluated for anti-leishmanial activities against 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 (IC < 0.0128 μg/mL) and (IC < 0.0128 μg/mL), which showed extraordinary efficacy in an in vitro test and low cytotoxicities (CC > 10 μg/mL). The anti-leishmanial activities of and 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.
在本研究中，合成了 45 种马来酰亚胺，并评估了它们对 体外抗利什曼原虫活性和对 THP1 细胞的细胞毒性。所有化合物均表现出明显的抗利什曼原虫活性。在所测试的化合物中，有 10 种马来酰亚胺的抗利什曼原虫活性优于标准药物两性霉素 B，有 32 种马来酰亚胺的抗利什曼原虫活性优于标准药物喷他脒，特别是化合物 （IC < 0.0128 μg/mL）和 （IC < 0.0128 μg/mL），它们在体外试验中表现出非凡的疗效和低细胞毒性（CC > 10 μg/mL）。和 的抗利什曼原虫活性比两性霉素 B 强 10 倍。结构与活性关系（SAR）研究表明，与 3-甲基马来酰亚胺和 3,4-二氯马来酰亚胺相比，3,4-非取代马来酰亚胺显示出最强的抗利什曼原虫活性。与 3-甲基马来酰亚胺和 3,4-非取代马来酰亚胺相比，3,4-二氯马来酰亚胺的细胞毒性最小。结果表明，所报道的几种化合物是有前途的潜在抗利什曼病药物开发的先导化合物。
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