Faculty of Pharmaceutical Sciences, University of Campinas, 13083-859 Campinas, SP, Brazil.
Institute of Chemistry, University of Campinas, P.O.Box 6154, 13083-970 Campinas, SP, Brazil.
Molecules. 2020 Mar 27;25(7):1525. doi: 10.3390/molecules25071525.
The research of natural products has allowed for the discovery of biologically relevant compounds inspired by plant secondary metabolites, which contributes to the development of many chemotherapeutic drugs used in cancer treatment. leaves present a diverse phytochemical composition including flavonoids, phenolics, meroterpenoids, and triterpenes as the major bioactive constituents. Guajadial, a caryophyllene-based meroterpenoid, has been studied for potential anticancer effects tested in tumor cells and animal experimental models. Moreover, guajadial has been reported to have a mechanism of action similar to tamoxifen, suggesting this compound as a promisor phytoestrogen-based therapeutic agent. Herein, the anti-estrogenic action and anti-proliferative activity of guajadial is reported. The enriched guajadial fraction was obtained by sequential chromatographic techniques from the crude dichloromethane extract showing promising anti-proliferative activity in vitro with selectivity for human breast cancer cell lines MCF-7 and MCF-7 BUS (Total Growth Inhibition = 5.59 and 2.27 µg·mL, respectively). Furthermore, evaluation of anti-estrogenic activity in vivo was performed demonstrating that guajadial enriched fraction inhibited the proliferative effect of estradiol on the uterus of pre-pubescent rats. These results suggest a relationship between anti-proliferative and anti-estrogenic activity of guajadial, which possibly acts in tumor inhibition through estrogen receptors due to the compounds structural similarity to tamoxifen.
天然产物的研究使得人们能够发现受植物次生代谢产物启发的具有生物相关性的化合物，这些化合物为许多用于癌症治疗的化疗药物的发展做出了贡献。 叶具有包括类黄酮、酚类、倍半萜和三萜在内的多种植物化学组成，是主要的生物活性成分。 贝壳杉烯基倍半萜类化合物 Guajadial 已被研究用于测试其在肿瘤细胞和动物实验模型中的潜在抗癌作用。 此外，据报道 Guajadial 的作用机制类似于他莫昔芬，表明该化合物作为一种有前途的基于植物雌激素的治疗剂。 本文报道了 Guajadial 的抗雌激素作用和抗增殖活性。 通过从粗二氯甲烷提取物中进行顺序色谱技术获得了富含 Guajadial 的馏分，该馏分在体外显示出有希望的抗增殖活性，对人乳腺癌细胞系 MCF-7 和 MCF-7 BUS 具有选择性（总生长抑制率分别为 5.59 和 2.27 µg·mL）。 此外，还进行了体内抗雌激素活性评价，证明 Guajadial 富集馏分抑制了雌二醇对未成年大鼠子宫的增殖作用。 这些结果表明 Guajadial 的抗增殖和抗雌激素活性之间存在关系，由于化合物与他莫昔芬的结构相似，其可能通过雌激素受体在肿瘤抑制中发挥作用。
