Novel Microtubule-Targeting 7-Deazahypoxanthines Derived from Marine Alkaloid Rigidins with Potent in Vitro and in Vivo Anticancer Activities

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• 作者：Derek C. Medellin ; Qiong Zhou ; Robert Scott ; R. Matthew Hill ; Sarah K. Frail ; Ramesh Dasari ; Steven J. Ontiveros ; Stephen C. Pelly ; Willem A. L. van Otterlo ; Tania Betancourt ; Charles B. Shuster ; Ernest Hamel ; Ruoli Bai ; Daniel V. LaBarbera ; Snezna Rogelj ; Liliya V. Frolova ; Alexander Kornienko
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：January 14, 2016
• 年：2016
• 卷：59
• 期：1
• 页码：480-485
• 全文大小：407K
• ISSN：1520-4804

文摘

Docking studies of tubulin-targeting C2-substituted 7-deazahypoxanthine analogues of marine alkaloid rigidins led to the design and synthesis of compounds containing linear C2-substituents. The C2-alkynyl analogue was found to have double- to single-digit nanomolar antiproliferative IC₅₀ values and showed statistically significant tumor size reduction in a colon cancer mouse model at nontoxic concentrations. These results provide impetus and further guidance for the development of these rigidin analogues as anticancer agents.