Design, Synthesis, and Biological Evaluation of Novel Amyl Ester Tethered Dihydroartemisinin‐Isatin Hybrids as Potent Anti‐Breast Cancer Agents. Issue 3 (6th March 2023)

• Record Type: Journal Article
• Authors: Xu, Zhi; Zhang, Xiaoyan; Liu, Jie; Zhao, Shijia; Liu, Junna; Zhou, Wei
• Is Part Of: Chemistry & biodiversity. Volume 20:Issue 3(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-03-06
• Subjects: dihydroartemisinin -- isatin -- hybrid molecules -- breast cancer -- drug resistance; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Biodiversity -- Periodicals; 572
• DOI: 10.1002/cbdv.202201257
• Languages: English
• ISSNs: 1612-1872

Abstract

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. Abstract : In this article, twelve amyl ester tethered dihydroartemisinin‐isatin hybrids were designed, synthesized, and assessed for their antiproliferative activity against ER‐positive (MCF‐7 and MCF‐7/ADR) and triple‐negative (MDA‐MB‐231 and MDA‐MB‐231/ADR) breast cancer cell lines in this article. Among them, 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, indicating their excellent selectivity and safety profiles.