Wang, Qinghui; Arnst, Kinsie E.; Wang, Yuxi; Kumar, Gyanendra; Ma, Dejian; White, Stephen W.; Miller, Duane D.; Li, Weimin; Li, Wei published the artcile< Structure-Guided Design, Synthesis, and Biological Evaluation of (2-(1H-Indol-3-yl)-1H-imidazol-4-yl)(3,4,5-trimethoxyphenyl) Methanone (ABI-231) Analogues Targeting the Colchicine Binding Site in Tubulin>, Application of C10H9NO, the main research area is ABI 231 analog design synthesis anticancer.
ABI-231 is a potent, orally bioavailable tubulin inhibitor that interacts with the colchicine binding site and is currently undergoing clin. trials for prostate cancer. Guided by the crystal structure of ABI-231 in complex with tubulin, we performed structure-activity relationship studies around the 3-indole moiety that led to the discovery of several potent ABI-231 analogs, most notably 10ab (I) and 10bb. The crystal structures of 10ab and 10bb in complex with tubulin confirmed their improved mol. interactions to the colchicine site. In vitro, biol. studies showed that new ABI-231 analogs disrupt tubulin polymerization, promote microtubule fragmentation, and inhibit cancer cell migration. In vivo, analog 10bb not only significantly inhibits primary tumor growth and decreases tumor metastasis in melanoma xenograft models but also shows a significant ability to overcome paclitaxel resistance in a taxane-resistant PC-3/TxR model. In addition, pharmacol. screening suggested that 10bb has a low risk of potential off-target function.
Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 4771-48-6 belongs to class indole-building-block, and the molecular formula is C10H9NO, Application of C10H9NO.
Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles