Active components from Cassia abbreviata prevent HIV-1 entry by distinct mechanisms of action.

  • HIV Clinical and Translational Research
  • Immuno-Pharmacology and Interactomics
May 10, 2021 By:
  • Zheng Y
  • Yang XW
  • Schols D
  • Mori M
  • Botta B
  • Chevigne A
  • Mulinge M
  • Steinmetz A
  • Schmit JC
  • Seguin-Devaux C.

Cassia 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 of C. 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-(4alpha-->8)-epiafzelechin, and a novel compound named as cassiabrevone. We report, for the first time, that guibourtinidol-(4alpha-->8)-epiafzelechin and cassiabrevone inhibit HIV-1 entry (IC50 of 42.47 microM and 30.96 microM, 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-(4alpha-->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.

2021 May. Int J Mol Sci.22(9):5052.
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