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

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.

Indoline alkaloids from Tabernaemontana contorta with cancer chemopreventive activity.

Two bisindoline alkaloids, contortarine A, 16-epi-pleiomutinine and a reaction product of pleiomutinine, namely N4-chloromethyl-pleiomutinine, were isolated from the roots of Tabernaemontana contorta Stapf. together with five known compounds: pleiomutinine, 1-carbomethoxy-ß-carboline, strictosidine lactam, pleiocarpamine, and pleiocarpine. The structures and relative configuration of these alkaloids were determined by extensive 1D and 2D NMR, and MS measurements. The absolute configuration of these compounds was determined by comparison of experimental and calculated ECD spectra. Among the isolated compounds, contortarine A, 1-carbomethoxy-ß-carboline and strictosidine lactam presented cancer chemopreventive properties through either quinone reductase (QR) induction with CD values of 16.0 ± 2.5, 30.2 ± 6.1 and 23.1 ± 4.6 µM, respectively, while pleiomutinine and 16-epi-pleiomutinine displayed the inhibition of TNF-α induced NF-κB activity with IC50 at 11.7 ± 2.6 and 3.4 ± 1.1 µM, respectively.

New flavonoids C-glycosides from Rhabdophyllum arnoldianum.

Two new flavone glycosides, 3″-O-acetyl-7-O-methylvitexin (1) and 6″-α-rhamnopyranosyl-7-O-methylvitexin (2), along with nine known compounds (3-11) were isolated from the leaves of Rhabdophyllum arnoldianum (Ochnaceae). The structures of the new compounds were established by detailed spectroscopic studies and mass spectrometry, while known compounds were characterised by direct comparison of their reported NMR data with those found in the literature. All these compounds were the first reported from Rhabdophyllum genus. The biological assays on crude extracts and compounds of this plant demonstrated that the crude extracts possess significant antimicrobial activity against Gram-positive bacteria.

Phenolic dimers and an indole alkaloid from Campylospermum flavum (Ochnaceae).

From the leaves and stem bark of Campylospermum flavum (Ochnaceae), three compounds, namely 4‴-O-methylagathisflavone, flavumchalcone, and flavumindole have been isolated together with 10 known compounds, including three flavonoids, two biflavonoids, two alkaloids, two nitrile glucosides, and glucopyranosyl-ß-sistosterol. The structures of these compounds and their relative configurations were established by 1D and 2D NMR experiments. The methanolic crude extracts of leaves and stem bark of C. flavum and compounds displayed a significant cytotoxicity towards Artemia salina larvae.