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

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• 作者：Wen-Tai Li ; Der-Ren Hwang ; Jen-Shin Song ; Ching-Ping Chen ; Jiunn-Jye Chuu ; Chih-Bo Hu ; Heng-Liang Lin ; Chen-Lung Huang ; Chiung-Yi Huang ; Huan-Yi Tseng ; Chu-Chung Lin ; Tung-Wei Chen ; Chi-Hung Lin ; Hsin
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：March 25, 2010
• 年：2010
• 卷：53
• 期：6
• 页码：2409-2417
• 全文大小：1006K
• 年卷期：v.53,no.6(March 25, 2010)
• ISSN：1520-4804

文摘

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.