Jun Wang, Yan Wang, Zhenyu Li, Peng Zhan, Rujun Bai, Christophe Pannecouque, Jan Balzarini, Erik De Clercq and Xinyong Liu Pages 738 - 746 ( 9 )
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 µM). In addition, preliminary discussion on the activity results and molecular modeling of these new analogues were presented in this manuscript.
Drug design, guanidine indole synthesis, HIV-1 Tat, HIV-1 TAR, inhibitors.
Key Laboratory of Chemical Biology (Educational Ministry of China ) and Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhuaxi Road, Jinan 250012, China.