29500-86-5Relevant articles and documents
Design and synthesis of marine sesterterpene analogues as novel estrogen receptor α degraders for breast cancer treatment
Gong, Shuang,Hong, Kui,Liang, Jian-Jia,Liu, Ten-Yue,Qin, Kong-Ming,Xie, Bao-Hua,Yan, Jing-Jing,Yang, Liang,Yin, Yu-Ping,Yu, Wu-Lin,Zhou, Hai-Bing
, (2022/01/08)
Targeted protein degradation using small molecules 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 biological 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, with IC50 values of 0.41 μM against MCF-7 cell lines and 9.6-fold stronger than MHO7, was the most potential molecule. A whole-genome transcriptomic analysis 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.
Temporal and Triggered Evolution of Host-Guest Characteristics in Amphiphilic Polymer Assemblies
Rangadurai, Poornima,Molla, Mijanur Rahaman,Prasad, Priyaa,Caissy, Matthew,Thayumanavan
supporting information, p. 7508 - 7511 (2016/07/06)
An amphiphilic polymer with cleavable side chain and main chain functional groups has been designed and synthesized. Specific cleavage of either of its functional groups was found to have an effect on the morphology of the assembly. Degradation of the main chain is shown to cause morphology of the supramolecular assembly to evolve with time from a micelle-like assembly to a vesicular assembly. On the other hand, stimulus-induced cleavage of the side chains causes these nanoassemblies to disassemble. These temporal (main chain) and triggered (side chain) degradation processes have implications in the design of degradable polymers as supramolecular scaffolds for biological applications.
A lewis acid-promoted pinner reaction
Pfaff, Dominik,Nemecek, Gregor,Podlech, Joachim
supporting information, p. 1572 - 1577 (2013/10/22)
Carbonitriles and alcohols react in a Lewis acid-promoted Pinner reaction to carboxylic esters. Best results are obtained with two equivalents of trimethylsilyl triflate as Lewis acid. Good yields are achieved with primary alcohols and aliphatic or benzylic carbonitriles, but the straightforward synthesis of acrylates and benzoates starting with acrylonitrile and benzonitrile, respectively, is similarly possible. Phenols are not acylated under these reaction conditions. The method has been used for the first total synthesis of the natural product monaspilosin. In the reaction of benzyl alcohols variable amounts of amides are formed in a Ritter-type side reaction.
