Design and synthesis of marine sesterterpene analogues as novel estrogen receptor α degraders for breast cancer treatment was written by Liang, Jian-Jia;Yu, Wu-Lin;Yang, Liang;Xie, Bao-Hua;Qin, Kong-Ming;Yin, Yu-Ping;Yan, Jing-Jing;Gong, Shuang;Liu, Ten-Yue;Zhou, Hai-Bing;Hong, Kui. And the article was included in European Journal of Medicinal Chemistry in 2022.Formula: C4H10O3 This article mentions the following:
Targeted protein degradation using small mols. is an intriguing strategy for drug development. The marine sesterterpene compound MHO7 had been reported to be a potential ERα degradation agent. In order to further improve its biol. activity, two series of novel MHO7 derivatives with long side chains were designed and identified as novel selective estrogen receptor down-regulators (SERDs). The growth inhibition activity of the novel SERD compounds were significantly affected by the type and length of the side chain. Most of the derivatives were significantly more potent than MHO7 against both drug-sensitive and drug-resistant breast cancer cells. Among them, compound 16a (I), with IC50 values of 0.41μM against MCF-7 cell lines and 9.6-fold stronger than MHO7, was the most potent mol. A whole-genome transcriptomic anal. of MCF-7 cells revealed that the mechanism of 16a against MCF-7 cell was similar with that of MHO7. The estrogen signaling pathway was the most affected among the disturbed genes, but the ERα degradation activity of 16a was observed higher than that of MHO7. Other effects of 16a were confirmed similar with MHO7, which means that the basic mechanisms of the derivatives are the same with the ophiobolin backbone, i.e. the degradation of ERα is mediated via proteasome-mediated process, the induction of apoptosis and the cell cycle arrest at the G1 phase. Meanwhile, a decrease of mitochondrial membrane potential and an increase of cellular ROS were also detected. Based on these results, as a novel modified ophiobolin derived compound, 16a may warrant further exploitation as a promising SERD candidate agent for the treatment of breast cancer. In the experiment, the researchers used many compounds, for example, 2,2′-Oxybis(ethan-1-ol) (cas: 111-46-6Formula: C4H10O3).
2,2′-Oxybis(ethan-1-ol) (cas: 111-46-6) belongs to alcohols. Alcohols are among the most common organic compounds. They are used as sweeteners and in making perfumes, are valuable intermediates in the synthesis of other compounds, and are among the most abundantly produced organic chemicals in industry. Converting an alcohol to an alkene requires removal of the hydroxyl group and a hydrogen atom on the neighbouring carbon atom. Dehydrations are most commonly carried out by warming the alcohol in the presence of a strong dehydrating acid, such as concentrated sulfuric acid.Formula: C4H10O3
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts