Tailoring 3,3′‐Dihydroxyisorenieratene to Hydroxystilbene: Finding a Resveratrol Analogue with Increased Antiproliferation Activity and Cell Selectivity |
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Authors: | Yan‐Fei Kang Wen‐Jing Yan Ting‐Wen Zhou Dr. Fang Dai Dr. Xiu‐Zhuang Li Xia‐Zhen Bao Yu‐Ting Du Cui‐Hong Yuan Hai‐Bo Wang Xiao‐Rong Ren Dr. Qiang Liu Dr. Xiao‐Ling Jin Prof. Dr. Bo Zhou Prof. Dr. Jie Zhang |
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Affiliation: | 1. State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou 730000 (China), Fax: (+86)?931‐8915557;2. Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen, Fujian 361102 (China) |
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Abstract: | Four novel compounds were designed by “tailoring” 3,3′‐dihydroxyisorenieratene (a natural carotenoid) based on an isoprene unit retention truncation strategy. Among them, the smallest molecule 1 (2,3,6,2′,3′,6′‐hexamethyl‐4,4′‐dihydroxy‐trans‐stilbene) was concisely synthesized in a one‐pot Stille–Heck tandem sequence, and surfaced as a promising lead molecule in terms of its selective antiproliferative activity mediated by blocking the NCI‐H460 cell cycle in G1 phase. Additionally, theoretical calculations and cell uptake experiments indicate that the unique polymethylation pattern of compound 1 significantly induces a conformational change shift out of planarity and increases its cell uptake and metabolic stability. The observation should be helpful to rationally design resveratrol‐inspired antiproliferative agents. |
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Keywords: | antiproliferation cell cycle isoprene units methylation reactions resveratrol |
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