Computational Studies Of Quinolinonvl Diketo Acid Derivatives As HIV Integrase Strand Transfer Inhibitors

Acquired immunodeficiency syndrome (AIDS), a disease derived from infection with human immunodeficiency virus 1 (HIV-1), is a severe threat to human health. Human immunodeficiency virus type 1 integrase is a novel target for the treatment of acquired immune deficiency syndrome. In this work, a series of quinolinonyl diketo acid derivatives as integrase strand transfer inhibitors was investigated using computational chemistry tools,including three-dimensional quantitative structure-activity relationship, pharmacophore, and molecular docking simulations. Three alignment rules were used to develop efficient models,which showed predictive ability with statistically significant parameters (q2 > 0.5, r2 > 0.9).The optimal comparative molecular field analysis models obtained q2 = 0.817 and r2 = 0.961,and the optima) comparative molecular similarity index analysis achieved q2 = 0.742 and r2 =0.967. The contour maps aided in understanding structural features that affect inhibitory activity against integrase. In addition, pharmacophore modeling was applied to find common features of integrase strand transfer inhibitors, and the results indicated the importance of quinolinonyl diketo acid structure. Moreover, molecular docking interpreted the interactions between compounds and integrase at active sites, which made a better understanding of the substituent groups on the benzene ring. These work would give a guide for the designation of new integrase strand transfer inhibitors.