Active Components from Cassia abbreviata Prevent HIV-1 Entry by Distinct Mechanisms of Action

Abstract

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 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.

Identification of Small Molecular Chaperones Binding P23H Mutant Opsin through an In Silico Structure-Based Approach

“…Different libraries of compounds were selected for virtual screening, including (1) a high diversity in-house library of around 1000 natural products, (2) the DrugBank database (around 2509 approved drugs), and (3) the commercially available MolPort database (around 8 million compounds) . Natural products are a unique and privileged source of hit/lead compounds with a wide chemical diversity as well as tools for understanding the chemical biology of protein targets. , In this context, natural products are largely used in virtual screening and drug design approaches carried out by our research group, showing remarkable pharmacological activities mostly as antiviral or anti-cancer drug candidates. − The DrugBank database was selected with the purpose of repositioning approved drugs, which is a widely used strategy that allows the therapeutic exploitation of a drug for a therapeutic indication that is different from that of its approval. − Finally, the MolPort database is a rich source of commercially available diverse structures for screening purposes. While screening libraries (1) and (2) was achieved at a relatively low computation cost, screening the MolPort database containing around 8 million compounds might require much more time and resources to be completed.…”

An insight into novel therapeutic potentials of taxifolin

“…The IC50 of taxifolin extracted from Cassia abbreviata is 49.04μM, exhibiting strong anti-HIV-1 activity ( Yang et al, 2021 ). Additionally, six substances, including taxifolin isolated from the alcohol crude extract of C. abbreviata root and bark, can block HIV-1 entry into cells ( Zheng et al, 2021 ).…”

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“…[80] Three compounds guibourtinidol-(4α→8)epiafzelechin and cassiabrevone inhibit HIV-1 entry (IC 50 of 42.47 µM and 30.96 µM, respectively), as well as that piceatannol interacts with cellular membranes. Cassiabrevone plays a major role of the crude extract of CA by blocking the binding activity of HIV-1 gp120 and CD4 [81] [Figure 1].…”