Design, Synthesis and Biological Evaluation of Substituted Guanidine Indole Derivatives as Potential Inhibitors of HIV-1 Tat-TAR Interaction

作者：Wang, Jun; Wang, Yan; Li, Zhenyu; Zhan, Peng; Bai, Rujun; Pannecouque, Christophe; Balzarini, Jan; De Clercq, Erik; Liu, Xinyong^*

来源：Medicinal Chemistry, 2014, 10(7): 738-746.

DOI：10.2174/1573406410666140306151815

• Drug design
• guanidine indole synthesis
• HIV-1 Tat
• HIV-1 TAR
• inhibitors

The interaction between the HIV-1 transactivator protein Tat and RNA response element (TAR) plays a critical role in HIV-1 transcription. Based on the pharmacophore model of reported inhibitors, a series of novel substituted guanidine indole derivatives was designed, synthesized and evaluated for their in vitro HIV-1 and HIV-2 inhibitory activity using the IIIB strain and ROD strain, respectively. Preliminary biological evaluation indicated that three compounds exhibited marked inhibitory activity against HIV-1 IIIB. Quite unexpectedly, compound a-7 was also endowed with the moderate anti-HIV-2 potency (EC50 = 58.14 mu M). In addition, preliminary discussion on the activity results and molecular modeling of these new analogues were presented in this manuscript.

• 出版日期2014
• 单位河北医科大学; 山东大学