Synthesis and Evaluation of 3-(1,3-dioxoisoindolin-2-yl)-N-substituted Phenyl Benzamide Analogues as HIV Integrase Strand Transfer Inhibitors

摘要

Background: A series of novel 3-(1,3-dioxoisoindolin-2-yl)-N-substituted phenyl benzamidederivatives was synthesized and tested in vitro against human immunodeficiency virustype-1 Integrase (HIV-1 IN).Methods: Out of the 18 analogues, six (compounds 16c, 16h, 16i, 16m, 16n and 16r) showed significantinhibition of strand transfer by HIV-1 integrase. For these six compounds. IC50 was below5.0 μM. In silico docking studies revealed that the presence of 2-phenyl isoindoline-1,3-dione motifwas essential as it was found to interact with active site magnesium.Results: To further confirm the results, cell-based HIV-1 and HIV-2 inhibitory assay was carried out.Conclusion: These compounds possess structural features not seen in previously reported HIV-1integrase inhibitors and thus can help further optimization of anti-HIV-1 integrase activity.