Zhou Xin-Ying, Cao Jing, Han Chao-Ming, Li Shu-Wen, Zhang Chen, Du Yin-Duan, Zhou Qian-Qian, Zhang Xin-Yan, Chen Xin
Beijing Institute of Dental Research, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, PR China.
School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Jiangsu 213164, PR China.
Bioorg Chem. 2017 Apr;71:74-80. doi: 10.1016/j.bioorg.2017.01.013. Epub 2017 Jan 22.
Garcinol from the fruit rind of Garcinia indica shows anti-carcinogenic and anti-inflammatory properties, but its mechanism and key functional groups were still need to be identified. Our previous computer modeling suggested that the C8 side chain of Garcinol is so large that it may influence the bioactivity of the compound. 8-Me Garcinol, a derivative of Garcinol in which the bulky side chain at the C8 position of Garcinol is replaced with a much smaller methyl group, was synthesized through a 12-step procedure starting from 1,3-cyclohexanedione. The antitumor activity of Garcinol and 8-Me Garcinol was evaluated in vitro by MTT, cell cycle and cell apoptosis assays. The results showed that 8-Me Garcinol had weaker inhibitory activity on cells proliferation, and little effects on cell cycle and apoptosis in oral cancer cell line SCC15 cells when compared with Garcinol. All of the results indicated 8-Me Garcinol exerts weaker antitumor activity than Garcinol, and the C8 side chain might be an important active site in Garcinol. Changing the C8 side chain will affect the inhibitory effect of Garcinol.
来自印度藤黄果皮的藤黄脂素具有抗癌和抗炎特性，但其作用机制和关键官能团仍有待确定。我们之前的计算机模拟表明，藤黄脂素的C8侧链很大，可能会影响该化合物的生物活性。8-甲基藤黄脂素是藤黄脂素的一种衍生物，其中藤黄脂素C8位置上庞大的侧链被一个小得多的甲基取代，它是从1,3-环己二酮开始通过12步合成的。通过MTT、细胞周期和细胞凋亡试验在体外评估了藤黄脂素和8-甲基藤黄脂素的抗肿瘤活性。结果表明，与藤黄脂素相比，8-甲基藤黄脂素对口腔癌细胞系SCC15细胞的增殖抑制活性较弱，对细胞周期和凋亡的影响较小。所有结果表明，8-甲基藤黄脂素的抗肿瘤活性比藤黄脂素弱，C8侧链可能是藤黄脂素的一个重要活性位点。改变C8侧链会影响藤黄脂素的抑制作用。
