Synthesis and HIV-1 Integrase Inhibition of Novel Bis or Tetra-Coumarin Analogues

• Published in: Chemical & Pharmaceutical Bulletin Vol. 55; no. 12; pp. 1740 - 1743
• Main Authors: Chih-Chia CHIANGa, Jean-Francois MOUSCADETb, Hou-Jen TSAIa, Chi-Tsan LIUc, Ling-Yih HSU, d
• Format: Journal Article
• Language: Japanese
• Published: Pharmaceutical Society of Japan 2007
• ISSN: 0009-2363

Present studies were undertaken on the preparation of synthetic analogues of bis or tetra-coumarins and their activity against HIV-1 integrase (HIV-1 IN). Among these coumarin analogues, compounds 14, 16 and 18 were found to be potent molecules against HIV-1 IN at IC50 values of 0.96, 0.58, and 0.49μM, respectively. The results provided a tool for guiding the further design of more potent antiviral agents and for predicting the affinity of related compounds. Acquired immuno-deficiency syndrome (AIDS) is a major pandemic caused by human immuno-deficiency virus (HIV) and considerable efforts are being completed for years to build up drugs against the outrageous disease. The HIV genome encodes for the protease, reverse transcriptase and integrase enzymes. Combination antiviral therapy with protease and reverse transcriptase inhibitors has established the potential therapeutic usefulness of antiviral therapy for treatment for AIDS.1) However, the capability of HIV to rapidly develop drug resistance, together with toxicity problems, requires the expansion of additional classes of antiviral drugs.