Medicinal Chemistry

Honorary Life Fellow
Kings College
University of Cambridge


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

Author(s): Jun Wang, Yan Wang, Zhenyu Li, Peng Zhan, Rujun Bai, Christophe Pannecouque, Jan Balzarini, Erik De Clercq and Xinyong Liu

Affiliation: 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.


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.

Keywords: Drug design, guanidine indole synthesis, HIV-1 Tat, HIV-1 TAR, inhibitors.

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Article Details

Page: [738 - 746]
Pages: 9
DOI: 10.2174/1573406410666140306151815