Studies On Synthesis And Biological Activity Of Indole Derivatives

Indole alkaloids are widespread in the nature,which also account for the largest proportion of the found alkaloids.Because of the complexity and diversity architectures,indole alkaloids showed a wide range of biological activities,including anti-tumor,antibacterial,and antiviral.Specially,several indole alkaloids have been approved as the first-line drugs for the treatment of disease.With a novel indolo[3,2-a] carbazole skeleton,Cytotoxic Racemosin B was isolated from green alga in2013 for the first time.Our research focused on the study of Racemosin B,which consisted of two parts below.Firstly,compounds with indolo [3,2-a] carbazole structure represent a small part of carbazole alkaloids,synthesis study on construction of indolo [3,2-a] carbazole a skeleton is still rare.Therefore,we summarized the synthesis routes of indolo [3,2-a]carbazole.Then,we established a method for building Racemosin B.2,4-dibromobenzoic acid as starting material reacted with different anilines to obtain the intermediate compound 32,then compound 32 was converted to Racemosin B through the palladium catalyzed oxidative coupling.In order to verify the applicability of the method,we synthesized 16 different Racemosin B derivatives.Secondly,on the basis of synthesis route to indolo [3,2-a] carbazole seleton,we introduced various of pharmacophores to Racemosin B.All synthetic compounds showed varying degrees of cytotoxic activities in vitro against five human cancer cell lines(K 562,PC-3,MDA-MB-231,MCF-7,WM-9)by using MTT method.Followed by comparing the results,we made a raw discussion of the structure-activity relationship of Racemosin B derivatives.At the same time,the drug with good physical and chemical properties and metabolic stability was selected as the lead compound.This provide the material basis and scientific basis for furtherdevelopment of antitumor medicines.As results,compounds YZC-448,YZC-474,YZC-441 and YZC-467 were capable of stronger inhibitory effects than others,with IC50 ranging from 0.07 to 3.39?mol/L.