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