TY - JOUR
T1 - In Vitro and In Silico Potential Inhibitory Effects of New Biflavonoids from Ochna rhizomatosa on HIV-1 Integrase and Plasmodium falciparum
AU - Messi, Angélique Nicolas
AU - Bonnet, Susan Lucia
AU - Owona, Brice Ayissi
AU - Wilhelm, Anke
AU - Kamto, Eutrophe Le Doux
AU - Ndongo, Joseph Thierry
AU - Siwe-Noundou, Xavier
AU - Poka, Madan
AU - Demana, Patrick H.
AU - Krause, Rui W.M.
AU - Ngo Mbing, Joséphine
AU - Pegnyemb, Dieudonné Emmanuel
AU - Bochet, Christian G.
N1 - Funding Information:
Part of this research was funded by the University of Fribourg in Switzerland via the postdoctoral research scholarship and also by TWAS (The World Academic of Science) with financial support (No 13-174 RG/CHE/AF/AC_G; UNESCO FR: 3240277733).
Funding Information:
The authors would like to thank the University of Fribourg in Switzerland for the postdoctoral research scholarship provided to Angelique Nicolas MESSI, the Department of Organic Chemistry of the University of the Free State, South Africa, for the fellowship and the University of Cape Town for the antimalarial assay. We are also grateful to the following organizations and institutions: TWAS (The World Academic of Science for financial support (No. 13-174 RG/CHE/AF/AC_G; UNESCO FR: 3240277733), the research group of Pegnyemb, the South African Medical Research Council (MRC) with funds from National Treasury under its Economic Competitiveness and Support package, and Sandisa Imbewu from Rhodes University for the anti-HIV activity. The authors would also like to thank Fawa Guidawa from the University of Ngaoundéré for assisting with the plant collection and identification.
Publisher Copyright:
© 2022 by the authors.
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
KW - HIV-1 replication
KW - Ochna rhizomatosa
KW - Plasmodium falciparum NF54
KW - biflavonoids
KW - molecular docking
KW - structure–activity relationships
UR - http://www.scopus.com/inward/record.url?scp=85137392675&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics14081701
DO - 10.3390/pharmaceutics14081701
M3 - Article
C2 - 36015326
AN - SCOPUS:85137392675
SN - 1999-4923
VL - 14
JO - Pharmaceutics
JF - Pharmaceutics
IS - 8
M1 - 1701
ER -