C15-Imines of Natural Matrine Alkaloid as Anti-HIV-1 Agents

Background: Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) have resulted in a global health threat. Meanwhile, due to the emergence of drug-resistant HIV-1 strains, the discovery of potent compounds for antiretroviral therapy success is highly desirable.Objective: This study aimed to develop anti-HIV-1 candidates which can be effectively applied for the treatment of HIV infection.Methods: Based upon our previous results, a series of E isomers of C15-imines of matrine (3a-l) were semi-synthesized from a natural quinolizidine alkaloid matrine. Their anti-HIV-1 activities were evaluated against HIV-1IIIB replication in acutely infected C8166 cells in vitro.Results: Derivatives 3c, 3h and 3j showed good anti-HIV-1 activities with EC50 and therapeutic index (TI) values of 0.0089/0.012/0.0091 mM, and 23.71/32.49/27.43, respectively.Conclusion: The substituents and their corresponding positions on the phenyl ring of C15-imine derivatives of matrine were vital for anti-HIV-1 activities. Compounds 3c, 3h and 3j can be used as leads for further structural modification as HIV-1 inhibitors.