HIV-1 Integrase Inhibitors: Design Synthesis And Biological Activities

Three enzymes play the key roles in the life cycle of human immunodeficiency virus (HIV), HIV-1 integrase catalyzes the integration of DNA replication of the viral genome into the host genome and there is no known analogue in the human cells. Therefore, integrase is a potential target for the anti-HIV drug design.Integrase was selected as the studying target, employed the computer-aided drug design method to make rational design and modification. Finally, two leading compounds were consigned for synthesis.One is Nphenylsulfonyl-L-Leu- N-2-(benzo[d]thiazol) -acetamide, the other is N,N'-(1,4-piperazinediyldi-3,1-propanediyl) Bis [2-(2- thiophenyl)] -4- Quinoline carboxamide.In order to study the relationship of the structure and bioactivity, based on the structure of two leading compounds, we designed and synthesized two series derivatives of leading compounds. The formular of the compounds were illustrated as follows:â… :â…¡:All the compounds were tested by integrase enzyme linked immuno- sorbent assay (ELISA) for inhibitor screening in vitro. Four compounds showed better bioactivity. They are N-(4-methyl-phenylsulfonyl)-L-Leu-N-2-(benzo [d] thiazol)-acetamide, N-(4-methyl-phenylsulfonyl)-L-Phen-N-2-(benzo[d] thiazol)-acetamide, N,N'-(1,4-piperazinediyldi -3,1- prop anediyl) Bis[2-(2-thiophenyl)-6-methyl]-4-Quinolinecarboxamide and N,N'-(1,4-pipera zinediyl di-3,1-propanediyl) Bis (2-pheny1-6-methyl)-4-Quinoline car boxamide.