Active components from cassia abbreviata prevent hiv-1 entry by distinct mechanisms of action

Yue Zheng, Xian Wen Yang, Dominique Schols, Mattia Mori, Bruno Botta, Andy Chevigné, Martin Mulinge, André Steinmetz, Jean Claude Schmit, Carole Seguin-Devaux*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Cassia abbreviataC. abbreviata is widely used in Sub-Saharan Africa for treating many diseases, including HIV-1 infection. We have recently described the chemical structures of 28 compounds isolated from an alcoholic crude extract of barks and roots ofC. abbreviata, and showed that six bioactive compounds inhibit HIV-1 infection. In the present study, we demonstrate that the six compounds block HIV-1 entry into cells: oleanolic acid, palmitic acid, taxifolin, piceatannol, guibourtinidol-(4α→8)-epiafzelechin, and a novel compound named as cassiabrevone. We report, for the first time, that guibourtinidol-(4α→8)-epiafzelechin and cassiabrevone inhibit HIV-1 entry (IC50 of 42.47 µM and 30.96 µM, respectively), as well as that piceatannol interacts with cellular membranes. Piceatannol inhibits HIV-1 infection in a dual-chamber assay mimicking the female genital tract, as well as HSV infection, emphasizing its potential as a microbicide. Structure-activity relationships (SAR) showed that pharmacophoric groups of piceatannol are strictly required to inhibit HIV-1 entry. By a ligand-based in silico study, we speculated that piceatannol and norartocarpetin may have a very similar mechanism of action and efficacy because of the highly comparable pharmacophoric and 3D space, while guibourtinidol-(4α→8)-epiafzelechin and cassiabrevone may display a different mechanism. We finally show that cassiabrevone plays a major role of the crude extract of CA by blocking the binding activity of HIV-1 gp120 and CD4.

Original languageEnglish
Article number5052
JournalInternational Journal of Molecular Sciences
Volume22
Issue number9
DOIs
Publication statusPublished - 10 May 2021

Keywords

  • Cassia abbreviata
  • HIV-1 entry
  • Natural products
  • Norartocarpetin
  • Pharmacophoric studies
  • Piceatannol
  • Structure-activity relationship

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