Department of Chemical Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, Via Santa Sofia 97, 95123 Catania, Italy.
Molecules. 2020 Feb 7;25(3):733. doi: 10.3390/molecules25030733.
Honokiol (2) is a natural bisphenol neolignan showing a variety of biological properties, including antitumor activity. Some studies pointed out 2 as a potential anticancer agent in view of its antiproliferative and pro-apoptotic activity towards tumor cells. As a further contribution to these studies, we report here the synthesis of a small library of bisphenol neolignans inspired by honokiol and the evaluation of their antiproliferative activity. The natural lead was hence subjected to simple chemical modifications to obtain the derivatives 3-9; further neolignans (12a-c, 13a-c, 14a-c, and 15a) were synthesized employing the Suzuki-Miyaura reaction, thus obtaining bisphenols with a substitution pattern different from honokiol. These compounds and the natural lead were subjected to antiproliferative assay towards HCT-116, HT-29, and PC3 tumor cell lines. Six of the neolignans show GI values lower than those of 2 towards all cell lines. Compounds 14a, 14c, and 15a are the most effective antiproliferative agents, with GI in the range of 3.6-19.1 µM, in some cases it is lower than those of the anticancer drug 5-fluorouracil. Flow cytometry experiments performed on these neolignans showed that the inhibition of proliferation is mainly due to an apoptotic process. These results indicate that the structural modification of honokiol may open the way to obtaining antitumor neolignans more potent than the natural lead.
和厚朴酚（2）是一种天然的双酚新木脂素，具有多种生物学特性，包括抗肿瘤活性。一些研究指出，2 因其对肿瘤细胞的增殖抑制和促凋亡活性，可作为一种潜在的抗癌药物。作为对这些研究的进一步贡献，我们在此报告了受和厚朴酚启发合成的一系列双酚新木脂素文库，并评估了它们的抗肿瘤活性。因此，对天然先导化合物进行了简单的化学修饰，得到了衍生物 3-9；进一步采用 Suzuki-Miyaura 反应合成了新木脂素（12a-c、13a-c、14a-c 和 15a），从而得到了与和厚朴酚取代模式不同的双酚。将这些化合物和天然先导化合物进行了 HCT-116、HT-29 和 PC3 肿瘤细胞系的增殖抑制测定。其中 6 种新木脂素对所有细胞系的 GI 值均低于 2。化合物 14a、14c 和 15a 是最有效的抗肿瘤剂，GI 值在 3.6-19.1 μM 范围内，在某些情况下低于抗癌药物 5-氟尿嘧啶。对这些新木脂素进行的流式细胞术实验表明，增殖抑制主要是由于凋亡过程。这些结果表明，和厚朴酚的结构修饰可能为获得比天然先导化合物更有效的抗肿瘤新木脂素开辟了道路。
