Wang, Lei; Fang, Kun; Cheng, Junfei; Li, Yu; Huang, Yahui; Chen, Shuqiang; Dong, Guoqiang; Wu, Shanchao; Sheng, Chunquan published the artcile< Scaffold Hopping of Natural Product Evodiamine: Discovery of a Novel Antitumor Scaffold with Excellent Potency against Colon Cancer>, Application In Synthesis of 399-76-8, the main research area is colon cancer antitumor agents SAR topoisomerase tubulin scaffold apoptosis.
Inspired by the natural product evodiamine, a novel antitumor indolopyrazinoquinazolinone scaffold was designed by scaffold hopping. Structure-activity relationship studies led to the discovery of compound 15j, which shows low nanomolar inhibitory activity against the HCT116 cell line. Further antitumor mechanism studies indicated that compound 15j acted by the dual inhibition of topoisomerase 1 and tubulin and induced apoptosis with G2 cell-cycle arrest. The quaternary ammonium salt of compound 15j (compound 15js) exhibited excellent in vivo antitumor activity (TGI = 66.6%) in the HCT116 xenograft model with low toxicity. Indolopyrazinoquinazolinone derivatives represent promising multitargeting antitumor leads for the development of novel antitumor agents.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 399-76-8 belongs to class indole-building-block, and the molecular formula is C9H6FNO2, Application In Synthesis of 399-76-8.
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