Kang Yan-Fei, Yan Wen-Jing, Zhou Ting-Wen, Dai Fang, Li Xiu-Zhuang, Bao Xia-Zhen, Du Yu-Ting, Yuan Cui-Hong, Wang Hai-Bo, Ren Xiao-Rong, Liu Qiang, Jin Xiao-Ling, Zhou Bo, Zhang Jie
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou 730000 (China), Fax: (+86) 931-8915557.
Chemistry. 2014 Jul 14;20(29):8904-8. doi: 10.1002/chem.201403024. Epub 2014 Jun 12.
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.
基于异戊二烯单元保留截断策略，通过“剪裁”3,3'-二羟基异菌绿素（一种天然类胡萝卜素）设计了四种新型化合物。其中，最小的分子1（2,3,6,2',3',6'-六甲基-4,4'-二羟基反式芪）通过一锅法的施蒂勒-赫克串联反应简洁地合成出来，并且就其通过阻断NCI-H460细胞周期的G1期介导的选择性抗增殖活性而言，它成为了一个有前景的先导分子。此外，理论计算和细胞摄取实验表明，化合物1独特的多甲基化模式显著诱导了构象变化，使其平面度发生偏移，并增加了其细胞摄取和代谢稳定性。该观察结果应有助于合理设计受白藜芦醇启发的抗增殖剂。
