Synthesis and Biological Activities of 2-Amino-1-arylidenamino Imidazoles as Orally Active Anticancer Agents

作者：Wen-Tai Li, Der-Ren Hwang, Jen-Shin Song, Ching-Ping Chen, Ching-Ping Chen, Jiunn‐Jye Chuu, Chih-Bo Hu, Heng‐Liang Lin, Chiung-Yi Huang, Chen‐Lung Huang, Huan-Yi Tseng, Chu-Chung Lin, Tung-Wei Chen, Chi-Hung Lin, Hsin-Sheng Wang, Chien-Chang Shen, Chung-Ming Chang, Yu-Sheng Chao, Chiung-Tong Chen, Chiung-Tong Chen · 发表于：Journal of Medicinal Chemistry · 年份：2010 · DOI：10.1021/jm901501s · 被引用次数：44 · 研究领域：Click Chemistry and Applications、Synthesis and biological activity、Synthesis and Characterization of Heterocyclic Compounds

2-Amino-1-arylidenaminoimidazoles, a novel class of orally (po) active microtubule-destabilizing anticancer agents, were synthesized. The compounds were designed from a hit compound identified in a drug discovery platform by using cancer cell-based high throughput screening assay. Selective synthesized compounds exerted cell cytotoxicity against human cancer cells. The underlying mechanisms for the anticancer activity were demonstrated as interacting with the tubulins and inhibiting microtubule assembly, leading to proliferation inhibition and apoptosis induction in the human tumor cells. Furthermore, two compounds showed in vivo anticancer activities in both po and intravenously (iv) administered routes and prolonged the life spans of murine leukemic P388 cells-inoculated mice. These new po active antimitotic anticancer agents are to be further examined in preclinical studies and developed for clinical uses.