Design, synthesis of new β-carboline derivatives and their selective anti-HIV-2 activity

Bioorg Med Chem Lett. 2015 Mar 15;25(6):1232-5. doi: 10.1016/j.bmcl.2015.01.058. Epub 2015 Jan 30.

Abstract

In the present study, a new series of β-carboline derivatives were synthesized and evaluated for inhibition activity against both HIV-1 and HIV-2 strains. Among these reported analogues, surprisingly (1-phenyl-9H-pyrido[3,4-b]indol-3-yl)(4-p-tolylpiperazin-1-yl)methanone (7b), (4-(2-methoxyphenyl)piperazin-1-yl)(1-phenyl-9H-pyrido[3,4-b]indol-3-yl)methanone (7f), (4-(4-fluorophenyl)piperazin-1-yl)(1-phenyl-9H-pyrido[3,4-b]indol-3-yl)methanone (7k), (4-(2-fluorophenyl)piperazin-1-yl)(1-phenyl-9H-pyrido[3,4-b]indol-3-yl)methanone (7l) displayed selective inhibition of HIV-2 strain with EC50 values of 3.3, 3.2, 2.6 and 5.4μM, respectively, which are comparable with nucleoside reverse transcriptase inhibitors lamivudine and dideoxyinosine. As these analogues have not shown in vitro HIV-2 reverse transcriptase inhibition, it could be excluded as potential target for their specific anti-HIV-2 activity.

Keywords: HIV-1; HIV-2; Reverse transcriptase; β-Carboline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbolines / chemical synthesis
  • Carbolines / chemistry*
  • Carbolines / pharmacology
  • Drug Design*
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects
  • HIV-2 / drug effects
  • HIV-2 / enzymology
  • Humans
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • (4-(4-fluorophenyl)piperazin-1-yl)(1-phenyl-9H-pyrido(3,4-b)indol-3-yl)methanone
  • Carbolines
  • Piperazines
  • Reverse Transcriptase Inhibitors
  • reverse transcriptase, Human immunodeficiency virus 2
  • HIV Reverse Transcriptase