Anti-Leishmanial and Cytotoxic Activities of a Series of Maleimides: Synthesis, Biological Evaluation and Structure-Activity Relationship
Yongxian Fan,
Yuele Lu,
Xiaolong Chen,
Babu Tekwani,
Xing-Cong Li,
Yinchu Shen
Affiliations
Yongxian Fan
Institute of Fermentation Engineering, College of Biotechnology and Bioengineering, Zhejiang University of Technology, 18# Chaowang Road, Hangzhou 310032, China
Yuele Lu
Institute of Fermentation Engineering, College of Biotechnology and Bioengineering, Zhejiang University of Technology, 18# Chaowang Road, Hangzhou 310032, China
Xiaolong Chen
Institute of Fermentation Engineering, College of Biotechnology and Bioengineering, Zhejiang University of Technology, 18# Chaowang Road, Hangzhou 310032, China
Babu Tekwani
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
Xing-Cong Li
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
Yinchu Shen
Institute of Fermentation Engineering, College of Biotechnology and Bioengineering, Zhejiang University of Technology, 18# Chaowang Road, Hangzhou 310032, China
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 μg/mL) and 42 (IC50 < 0.0128 μg/mL), which showed extraordinary efficacy in an in vitro test and low cytotoxicities (CC50 > 10 μg/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.
