In Vitro and In Silico Potential Inhibitory Effects of New Biflavonoids from IOchna rhizomatosa/I on HIV-1 Integrase and IPlasmodium falciparum/I

• Published in: Pharmaceutics Vol. 14; no. 8
• Main Authors: Messi, Angélique Nicolas, Bonnet, Susan Lucia, Owona, Brice Ayissi, Wilhelm, Anke, Kamto, Eutrophe Le Doux, Ndongo, Joseph Thierry, Siwe-Noundou, Xavier, Poka, Madan, Demana, Patrick H, Krause, Rui W. M, Ngo Mbing, Joséphine, Pegnyemb, Dieudonné Emmanuel, Bochet, Christian G
• Format: Journal Article
• Language: English
• Published: MDPI AG 01.08.2022
• Subjects: Anti-infective agents; Bioflavonoids; Chemical properties; Dicotyledons; Drug therapy; Flavones; Flavonoids; Health aspects; HIV infection; Malaria; Pharmaceutical research; Plant metabolites; Cameroon
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics14081701

The aim of this study was to identify bioactive secondary metabolites from Ochna rhizomatosa with potential inhibitory effects against HIV and Plasmodium falciparum. A phytochemical study of O. rhizomatosa root barks resulted in the identification of three new biflavonoids (1–3), along with four known ones (4–7). Compound 7 (Gerontoisoflavone A) was a single flavonoid present in the rootbark of the plant and was used as a reference. Compound 1 (IC[sub.50] = 0.047 µM) was the only one with a noteworthy inhibitory effect against HIV-1 integrase in vitro. Chicoric acid (IC[sub.50] = 0.006 µM), a pure competitive inhibitor of HIV-1 integrase, was used as control. Compound 2 exhibited the highest antiplasmodial activity (IC[sub.50] = 4.60 µM) against the chloroquine-sensitive strain of Plasmodium falciparum NF54. Computational molecular docking revealed that compounds 1 and 2 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 1 and 2 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 1 and 2 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.