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

Angélique Nicolas Messi*, Susan Lucia Bonnet, Brice Ayissi Owona, Anke Wilhelm, Eutrophe Le Doux Kamto, Joseph Thierry Ndongo, Xavier Siwe-Noundou, Madan Poka, Patrick H. Demana, Rui W.M. Krause, Joséphine Ngo Mbing, Dieudonné Emmanuel Pegnyemb, Christian G. Bochet

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 (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 2 exhibited the highest antiplasmodial activity (IC50 = 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.

Original languageEnglish
Article number1701
JournalPharmaceutics
Volume14
Issue number8
DOIs
Publication statusPublished - Aug 2022
Externally publishedYes

Keywords

  • biflavonoids
  • HIV-1 replication
  • molecular docking
  • Ochna rhizomatosa
  • Plasmodium falciparum NF54
  • structure–activity relationships

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