Development of Cyclic N,O-Aminal-Embedded Bis-tetrahydroisoquinoline Analogues as Potential DNA Alkylation Agents
Min Wang1, Tianyang Wang1, Xuemei Qin1,2
1State Key Laboratory of Coordination Chemistry and Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, 163 Xianlin Avenue, Nanjing, Jiangsu 210023, China.
Abstract:
This work described a novel "functional hybrid" design for bis-tetrahydroisoquinoline (bis-THIQ) analogues as potential DNA alkylation agents by replacing the labile C21-carbinolamine on the bis-THIQ skeleton of ET-743 with a chemically stable cyclic N,O-aminal functionality. In vitro anti-proliferation evaluation has proven that it is a successful approach to deliver new bis-THIQ analogues with common cytotoxicities, among which several exhibited sub-micromolar-range IC50 against the proliferation of human cancer cell lines A549, HepG2, and MDA-MB-231, respectively.
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