Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
CIIMAR/CIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Edifício do Terminal de Cruzeiros do Porto de Leixões, Avenida General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal.
Molecules. 2020 Mar 30;25(7):1578. doi: 10.3390/molecules25071578.
Hierridin B (), a methylated hydroquinone isolated from the marine picocyanobacterium sp. LEGE 06113, moderately inhibited the growth of colon adenocarcinoma HT-29 cells. Aiming to improve the potential antitumor activity of this natural product, the demethylated analogue, norhierridin B (), as well as its structurally-related quinone (), were synthesized and evaluated for their growth inhibitory effect on a panel of human tumor cell lines, including the triple-negative breast cancer (TNBC) cells MDA-MB-231, SKBR3, and MDA-MB-468. Norhierridin B () showed a potent growth inhibitory effect on all cancer cell lines. Moreover, the growth inhibitory effect of compound on MDA-MB-231 cells was associated with cell cycle arrest and apoptosis. Norhierridin B () interfered with several p53 transcriptional targets, increasing p21, Bax, and MDM2, while decreasing Bcl-2 protein levels, which suggested the potential activation of a p53 pathway. Altogether, these results evidenced a great improvement of the antitumor activity of hydroquinone when compared to and its structurally-related quinone (). Notably, hydroquinone displayed a prominent growth inhibitory activity against TNBC cells, which are characterized by high therapeutic resistance.
希瑞丁 B（）是从海洋蓝藻 sp.LEGE 06113 中分离得到的一种甲基化对苯二酚，对结肠腺癌 HT-29 细胞的生长有一定的抑制作用。为了提高该天然产物的潜在抗肿瘤活性，对其脱甲基类似物，即去甲希瑞丁 B（）以及其结构相关的醌（）进行了合成，并对其在一组人类肿瘤细胞系中的生长抑制作用进行了评估，包括三阴性乳腺癌（TNBC）细胞 MDA-MB-231、SKBR3 和 MDA-MB-468。去甲希瑞丁 B（）对所有癌细胞系均表现出很强的生长抑制作用。此外，化合物对 MDA-MB-231 细胞的生长抑制作用与细胞周期停滞和细胞凋亡有关。去甲希瑞丁 B（）干扰了多个 p53 转录靶标，增加了 p21、Bax 和 MDM2 的表达，同时降低了 Bcl-2 蛋白水平，这表明可能激活了 p53 通路。总之，与 及其结构相关的醌（）相比，对苯二酚的抗肿瘤活性有了显著提高。值得注意的是，对苯二酚对 TNBC 细胞具有明显的生长抑制活性，而 TNBC 细胞的治疗耐药性很高。
