Design,Synthesis, and Biological Evaluation of Novel Amyl Ester Tethered Dihydroartemisinin-Isatin Hybrids as Potent Anti-Breast Cancer Agents |
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| Authors: | Zhi Xu Xiaoyan Zhang Jie Liu Shijia Zhao Junna Liu Wei Zhou |
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| Institution: | 1. School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550025 P. R. China;2. Department of Pharmacology, School of Medical Sciences, Guizhou Medical University, Guiyang, 550025, Guizhou P. R. China;3. Department of Pharmaceutical Analysis, School of Pharmacy, Guizhou Medical University, Guiyang, 550025, Guizhou P. R. China;4. School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan, 430081 P. R. China |
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| Abstract: | A series of novel amyl ester tethered dihydroartemisinin-isatin hybrids 4a–d and 5a–h were designed, synthesized, and evaluated as anti-breast cancer agents. The synthesized hybrids were preliminarily screened against estrogen receptor-positive (MCF-7 and MCF-7/ADR) and triple-negative (MDA-MB-231 and) breast cancer cell lines. Three hybrids 4a , d and 5e not only were more potent than artemisinin and adriamycin against drug-resistant MCF-7/ADR and MDA-MB-231/ADR breast cancer cell lines, but also displayed non-cytotoxicity towards normal MCF-10 A breast cells, and the SI values were >4.15, indicating their excellent selectivity and safety profiles. Thus, hybrids 4a , d and 5e could act as potential anti-breast cancer candidates and were worthy of further preclinical evaluations. Moreover, the structure–activity relationships which may facilitate further rational design of more effective candidates were also enriched. |
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| Keywords: | dihydroartemisinin isatin hybrid molecules breast cancer drug resistance |
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