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Medicinal Chemistry
ISSN (Print): 1573-4064
ISSN (Online): 1875-6638
Epub Full Text Article
DOI: 10.2174/1573406410666140306151815      Price:  $95









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

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Author(s): Jun Wang, Yan Wang, Rujun Bai, Peng Zhan, Christophe Pannecouque, Jan Balzarini, Erik De Clercq and Xinyong Liu
Abstract:
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 were designed, synthesized and evaluated for their in vitro HIV-1 and HIV-2 activity using the IIIB strain and ROD strain, respectively. Preliminary biological evaluation indicated that three compounds exhibited marked inhibitory activity 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
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