Design, Synthesis And Anti-HIV Activity Of Carbazole Compounds

Acquired immunodeficiency syndrome is a global epidemic disease caused by HIV infection.Since the identification of HIV virus,approximately 40 million people have died of AIDS,however,there is no cure for AIDS yet.Thus,the research focusing on the discovery of novel anti-HIV compounds is still very attractive and challenging.Carbazole alkaloids are important nitrogen-containing aromatic heterocyclic compounds possessing many biological activities,which are of great significance for drug development,some alkaloids or analogues bearing carbazole scaffold exhibited effective anti-HIV activity in the test.Considering the urgent need for new drugs and the few reports on anti-HIV activity of carbazole derivatives,a series of carbazole and biscarbazole compounds have been designed and synthesized on the basis of previous research for a profound study of their anti-HIV activity.The main work of this paper includes the following four parts:1.The advances in anti-HIV activities of carbazole derivatives and compounds bearing carbazole skeleton was introduced in detail.The occurrence,synthesis and bioactivity of biscarbazole alkalodis were summarized.2.Several substituent groups such as methyl,methoxy,nitro and hydroxyl were picked to modify the carbazole skeleton.Fifty-three monomer carbazole derivatives were synthesized using diphenylamine derivatives as intermediates,and the effects of cyano,nitro and trifluoromethyl groups on the regioselectivity of carbazole derivatives was also investigated during the process of synthesis.It was found that cyano and nitro groups,electron withdrawing substituents with conjugate structure,could induce the generation of C4-substituted carbazole compounds.This method could provide a helpful and concise synthetic route for the synthesis of C4-substituted carbazole derivatives.3.The synthesis of dimeric carbazole compounds was studied.Three inorganic oxidants(FeCl3,Ag2O,MnO2)and two free radical initiators(BPO,TBHP)have been used in the dimerization of carbazole compounds.The results showed that different carbazole compounds were difficult to generate dimer with one single oxidant,and only the suitable active oxidant can catalyze the dimerization of carbazole derivatives.Nine biscarbazoles were prepared by the oxidative coupling reaction of the free radicals mentioned above.4.The anti-HIV activity of forty carbazole derivatives was evaluated in MT-4 cells by MTT assay using AZT as the reference substance.The results showed that seven unilateral dimethoxy substituted carbazole compounds,such as C-31,C-35,C-36,C-37,C-38,C-41 and C-43,exhibited anti-HIV activity,the EC50 values of them range from 3.7± 1.9μg/mL to 6.2±2.1μg/mL,and the SI values of them were no less than 5 except C-37(CC50/EC50≥5).The other compounds are still under activity test.