Tailoring 3,3'-dihydroxyisorenieratene to hydroxystilbene: finding a resveratrol analogue with increased antiproliferation activity and cell selectivity.
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.
['Kang|Yan-Fei|YF|', 'Yan|Wen-Jing|WJ|', 'Zhou|Ting-Wen|TW|', 'Dai|Fang|F|', 'Li|Xiu-Zhuang|XZ|', 'Bao|Xia-Zhen|XZ|', 'Du|Yu-Ting|YT|', 'Yuan|Cui-Hong|CH|', 'Wang|Hai-Bo|HB|', 'Ren|Xiao-Rong|XR|', 'Liu|Qiang|Q|', 'Jin|Xiao-Ling|XL|', 'Zhou|Bo|B|', 'Zhang|Jie|J|']
D000972:Antineoplastic Agents, Phytogenic D002338:Carotenoids D002453:Cell Cycle D045744:Cell Line, Tumor D049109:Cell Proliferation D055808:Drug Discovery D006801:Humans D008958:Models, Molecular D000077185:Resveratrol D013267:Stilbenes
resveratrol antiproliferation isoprene units cell cycle methylation reactions