In Vitro and In Silico Potential Inhibitory Effects of New Biflavonoids from Ochna rhizomatosa on HIV-1 Integrase and Plasmodium falciparum

Abstract

The aim of this study was to identify bioactive secondary metabolites from <i>Ochna rhizomatosa</i> with potential inhibitory effects against HIV and <i>Plasmodium falciparum. A</i> phytochemical study of <i>O. rhizomatosa</i> root barks resulted in the identification of three new biflavonoids (<b>1</b>-<b>3</b>), along with four known ones (<b>4</b>-<b>7</b>). Compound <b>7</b> (Gerontoisoflavone A) was a single flavonoid present in the rootbark of the plant and was used as a reference. Compound <b>1</b> (IC₅₀ = 0.047 µM) was the only one with a noteworthy inhibitory effect against HIV-1 integrase in vitro. Chicoric acid (IC₅₀ = 0.006 µM), a pure competitive inhibitor of HIV-1 integrase, was used as control. Compound <b>2</b> exhibited the highest antiplasmodial activity (IC₅₀ = 4.60 µM) against the chloroquine-sensitive strain of <i>Plasmodium falciparum</i> NF<i>54</i>. Computational molecular docking revealed that compounds <b>1</b> and <b>2</b> had the highest binding score (-121.8 and -131.88 Kcal/mol, respectively) in comparison to chicoric acid and Dolutegravir (-116 and -100 Kcal/mol, respectively), towards integrase receptor (PDB:3LPT). As far as Plasmodium-6 cysteine s48/45 domain inhibition is concerned, compounds <b>1</b> and <b>2</b> showed the highest binding scores in comparison to chloroquine, urging the analysis of these compounds in vivo for disease treatment. These results confirm the potential inhibitory effect of compounds <b>1</b> and <b>2</b> for HIV and malaria treatment. Therefore, our future investigation to find inhibitors of these receptors in vivo could be an effective strategy for developing new drugs.