The Synthesis And Activity Of Diketoacid Lactones As HIV-1 Integrase Inhibitors

Human immunodeficiency virus type-1 (HIV-1) is the causative agent of acquired immunedeficiency syndrome (AIDS), which is one of the most serious health problems. HIV-1 is a retrovirus, whose life cycle depends on the fusion, transcriptase(RT), protease(PI), and integrase (IN). HIV-1 integrase catalyzes the integration of HIV-1 DNA cope into the host cell DNA. Integrate is essential for the process of virus integration, and there is no celluar homologue in human body, so HIV-1 integrase becomes an important target for AIDS therapeutics.In this paper, we synthesis the diketoacid lactones as HIV-1 integrase inhibitors. Studies involve the sketch design of the target compound based on the structure of HIV-1 integrase and the crystallatical model of 5-CITEP with HIV-1 integrase. With different acetophenones and ethyl oxalate as raw materials, a series of new compounds are synthesized by the reaction of condensation, alcoholysis and so on. The chemical structures of these compounds are confirmed by IR, MS, and ~1H-NMR spectras. Anti-HIV-1 integrase assay of the compounds is carried out by experiment in vitro. The test result suggestes that all compounds show potent HIV-1 integrase inhibitory activity .The structure-activity relationships of these compounds are developed.In conclusion, we have synthesized and tested the inhibitory activity of a new type of HIV-1 integrase inhibitors, which contains...