Design,Synthesis,Evaluation Of Anticancer Activity And SAR Studies Of Novel Indole Pyrrole Methanes

The development of SIM+is based on bisindole methane compounds,which are derived from small molecule compounds found in cruciferous vegetables.They exert the biological effects of cell cycle arrest and apoptosis,which are equivalent to or better than that of bisindolemethane compounds,and have obvious antitumor effects as well.In this paper,pyrrole-substituted monoindole asymmetric methane compound was used as the hit molecule.Based on this structure,multiple sites are substituted with different groups.First,the synthesis method of SIM compounds was optimized,and 17 were obtained.And 19 SIM+ derivatives were synthesized.These structures of the compounds were characterized by 1H-NMR,13C-NMR and HR-MS.Based on the results of apoptosis activity evaluation of cancer cells completed by biology group in Dr.Zhang’s lab,we analyzed the structure-activity relationship of SIM+derivatives and concluded:1)When the mono-substitution modification on the benzene ring is carried out by keeping the indole ring and the pyrrole ring unchanged,the activity of the Ph-4CF3 substituted molecule is better than the Ph-3-CF3 substituted;2)The introduction of an electron-donor group on the indole ring is not conducive to the maintenance of antitumor activity,the introduction of a neutral group is conducive to the maintenance of its activity,and the introduction of an electron-withdrawing group is conducive to the enhancement of its activity where there is 4-CF3 on the benzene;3)For the pyrrole ring,the introduction of substituents is not conducive to maintaining its antitumor activity,which will lead to a significant reduction in the final antitumor activity;the structure-activity relationship of some other potential drug candidates and new compound backbones are being further explored.Based on the diversity of structural modifications of SIM+derivatives and the evaluation of their apoptotic activity in triple negative breast cancer cells.A number of lead compounds with significant apoptotic activity against triple negative breast cancer were optimized.For instance,XS-704,XS-891,XS-929.Raw materials for making these compounds are not only easy to obtain,but also the synthetic route is simple.Potentially they are expected to be better lead compounds for the development of clinical treatment of triple negative breast cancer.