In Vitro and In Silico Potential Inhibitory Effects of New Biflavonoids from <i>Ochna rhizomatosa</i> on HIV-1 Integrase and <i>Plasmodium falciparum</i>
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
Affiliations
Angélique Nicolas Messi
Department of Organic Chemistry, Faculty of Science, University of Yaounde I, Yaounde P.O. Box 812, Cameroon
Susan Lucia Bonnet
Department of Chemistry, University of the Free State, 205 Nelson Mandela Avenue, Bloemfontein 9301, South Africa
Brice Ayissi Owona
Department of Biochemistry, Faculty of Science, University of Yaounde I, Yaounde P.O. Box 812, Cameroon
Anke Wilhelm
Department of Chemistry, University of the Free State, 205 Nelson Mandela Avenue, Bloemfontein 9301, South Africa
Eutrophe Le Doux Kamto
Department of Organic Chemistry, Faculty of Science, University of Yaounde I, Yaounde P.O. Box 812, Cameroon
Joseph Thierry Ndongo
Department of Chemistry, Higher Teacher Training College, University of Yaounde 1, Yaounde P.O. Box 47, Cameroon
Xavier Siwe-Noundou
Department of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria 0204, South Africa
Madan Poka
Department of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria 0204, South Africa
Patrick H. Demana
Department of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria 0204, South Africa
Rui W. M. Krause
Nanomaterials and Medicinal Organic Chemistry Laboratory, Department of Chemistry, Rhodes University, Grahamstown 6140, South Africa
Joséphine Ngo Mbing
Department of Organic Chemistry, Faculty of Science, University of Yaounde I, Yaounde P.O. Box 812, Cameroon
Dieudonné Emmanuel Pegnyemb
Department of Organic Chemistry, Faculty of Science, University of Yaounde I, Yaounde P.O. Box 812, Cameroon
Christian G. Bochet
Department of Chemistry, University of Fribourg, Chemin du Musée 9, CH-1700 Fribourg, Switzerland
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.
