Novel synthetic 2-amino-10-(3,5-dimethoxy)benzyl-9(10H)-acridinone derivatives as potent DNA-binding antiproliferative agents

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• 作者：Chunmei Gao ; Feng Liu ; Xudong Luan ; Chunyan Tan ; Hongxia Liu ; Yonghua Xie ; Yibao Jin ; Yuyang Jiang
• 关键词：Acridinone derivatives ; Antiproliferative activity ; DNA binding ; Topoisomerase 1 inhibitor
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2010
• 出版时间：1 November 2010
• 年：2010
• 卷：18
• 期：21
• 页码：7507-7514
• 全文大小：853 K

文摘

A series of novel 9(10H)-acridinone derivatives with terminal amino substituents at C2 position on the acridinone ring were synthesized and studied for their antiproliferative activity and underlying mechanisms. These compounds demonstrated promising cytotoxicity to leukemia cells CCRF-CEM, displaying IC₅₀ values in the low micromolar range. Structure–activity relationships (SAR) indicated that the compound 6d bearing a pyrrolidine substituent and 8a with a methyl ammonium side chain displayed higher cytotoxicity to CCRF-CEM cells and also solid tumor cells A549, HepG2, and MCF7. Furthermore, the compounds 6d and 8a had strong binding activity to calf thymus DNA (ct DNA), as detected by UV absorption and fluorescence quenching assays, but limited inhibitory activity to human topoisomerase 1 (topo 1). Taken together, this study discovered a series of new synthetic 9(10H)-acridinone derivatives with potent DNA binding and anticancer activity.