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.

New triterpenoid saponin from the stems of Albizia adianthifolia (Schumach.) W.Wight.

As part of our continuing study of apoptosis-inducing saponins from Cameroonian Albizia genus, one new triterpenoid saponin, named adianthifolioside J (1), together with the known gummiferaoside E (2), were isolated from Albizia adianthifolia stems. The structure of the new saponin (1), was established on the basis of extensive analysis of 1 D and 2 D NMR (1H-, 13C-NMR, DEPT, COSY, TOCSY, NOESY, HSQC, HSQC-TOCSY and HMBC) and HRESIMS experiments, and by chemical evidence as 3-O-[ß-D-xylopyranosyl-(1→2)-ß-D-fucopyranosyl-(1→6)-ß-D-glucopyranosyl]-21-O-{(2E,6S)-2-(hydroxymethyl)-6-methyl-6-O-{4-O-[(2E,6S)-2,6-dimethyl-6-O-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]}acacic acid-28-O-ß-D-glucopyranosyl-(1→3)-[5-O-acetyl-α-L-arabinofuranosyl-(1→4)]-α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranosyl ester (1). The pro-apoptotic activity of the new isolated saponin 1 was evaluated, using Annexin V-FITC binding assay, on the A431 human epidermoid cancer cell. The result showed that adianthifolioside J (1) displayed weak pro-apoptotic activity.

Anti-breast cancer potential of Anonidium mannii (Oliv.) Engl. & Diels barks ethanolic extract: UPLC-ESI-QTOF-MS detection of anticancer alkaloids.

ETHNOPHARMACOLOGICAL RELEVANCE: Breast cancer is a serious threat in low-income as well as developed countries. To face this, many herbal preparations are prescribed by traditional healers in Cameroon, among which is Anonidium mannii commonly called "wild soursop". AIM: This study was undertaken to assess the anti-tumor effect of A. mannii ethanolic extract on cancer cell growth and against DMBA-induced mammary tumors in rats. MATERIALS AND METHODS: The well characterized MTT bioassay was used to assess the cytotoxic potential of A. mannii ethanolic extract in liver (HepG2), prostate (DU145 & PC3) and breast (MCF-7) cancer cell lines. Considering the fact that breast cells were the most sensitive to the extract, a 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast tumor rat model was used to assess the possible anticancer effect of A. mannii extract. Indeed, rats were treated with either tamoxifen (3.3 mg/kg BW) or A. mannii extract (16.5, 50 and 150 mg/kg BW) or vehicle (2% ethanol) for 20 weeks. Tumor incidence, tumor mass and volume, oxidative stress status in tumor as well as tumor histoarchitecture were evaluated. RESULTS: A 24 h incubation of tested cells with the A. mannii extract significantly slowed cell growth in a concentration-dependent manner with an interesting effect in breast cells (IC50 ~61.5 µg/mL). As compared to the DMBA rats, those treated with A. mannii extract (50 and 150 mg/kg) showed reduced breast tumor incidence (28%), tumor burden (95.34% at 50 mg/kg and 99.14% at 150 mg/kg) and tumor volume (~92%). A. mannii extract counteracted the high proliferation of terminal mammary ducts induced by DMBA, mainly at 50 mg/kg. Furthermore, the extract decreased MDA and nitrite levels but increased SOD activity in the mammary gland. High Performance Liquid Chromatography coupled with Mass Spectrometry (HPLC-MS) analysis detected potential anticancer and antioxidant alkaloids in A. manni extract, which are close to those found in Annona muricata. CONCLUSION: These results provide evidence on the in vitro and in vivo anticancer effects of A. mannii, and therefore support its use in traditional medicine system to fight against cancer.

Chemical constituents of the leaves of Anthonotha macrophylla (Leguminosae).

The present study deals with the isolation and the characterization of the chemical constituents from the leaves of Anthonotha macrophylla (Leguminosae). Using various chromatographic techniques (TLC, CC, HPLC), the methanolic extract of the leaves of Anthonotha macrophylla yielded one new alkaloid (1) as well as six known compounds amongst which an alkane (2), isolated for the first time from a natural product, an ester of fatty acid (3), two isocoumarines (4-5), a sterol (6) and a disaccharide (7). Their structures were elucidated using spectroscopic technics including extensive 1-D and 2-D NMR, HR-SM experiments.

Pro-apoptotic activity of new triterpenoid saponins from the roots of Albizia adianthifolia (Schumach.) W.Wight.

As part of our study of the proapoptotic function of saponins from Cameroonian's Albizia genus, phytochemical investigation of the roots of Albizia adianthifolia led to the isolation of three new triterpenoid saponins, named adianthifoliosides GI (13). Their structures were established on the basis of extensive analysis of 1D and 2D NMR (1H-, 13C NMR, DEPT, COSY, TOCSY, NOESY, HSQC, HSQC-TOCSY and HMBC) and HRESIMS experiments, and by chemical evidence as 3-O-[ß-d-glucopyranosyl-(1 → 2)-ß-D-fucopyranosyl-(1 → 6)-ß-d-glucopyranosyl]-21-O-{(2E,6S)-2-(hydroxymethyl)-6-methyl-6-O-{4-O-[(2E,6S)-2,6-dimethyl-6-O-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]}acacic acid-28-O-ß-d-xylopyranosyl-(1 → 3)-[5-O-acetyl-α-L-arabinofuranosyl-(1 → 4)]-α-L-rhamnopyranosyl-(1 → 2)-ß-d-glucopyranosyl ester (1), 3-O-[ß-d-glucopyranosyl-(1 → 2)-ß-D-fucopyranosyl-(1 → 6)-ß-d-glucopyranosyl]-21-O-{(2E,6S)-2-(hydroxymethyl)-6-methyl-6-O-{4-O-[(2E,6S)-2,6-dimethyl-6-O-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]}acacic acid 28-O-ß-d-xylopyranosyl-(1 → 3)-[α-L-arabinofuranosyl-1 → 4)]-α-L-rhamnopyranosyl-(1 → 2)-ß-d-glucopyranosyl ester (2), and 3-O-[ß-d-glucopyranosyl-(1 → 2)-ß-D-fucopyranosyl-(1 → 6)-ß-d-glucopyranosyl]-21-O-{(2E,6S)-2-(hydroxymethyl)-6-methyl-6-O-{4-O-[(2E,6S)-2,6-dimethyl-6-O-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]-4-O-[(2E,6S)-2,6-dimethyl-6-O-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]-ß-D-quinovopyranosyl}-2,6-dimethylocta-2,7-dienoyl}acacic acid 28-O-ß-d-xylopyranosyl-(1 → 3)-[α-L-arabinofuranosyl-1 → 4)]-α-L-rhamnopyranosyl-(1 → 2)-ß-d-glucopyranosyl ester (3). The apoptotic effect of saponins 1-3 was evaluated on the A431 human epidermoid cancer cell. Flow cytometric analyses showed that saponins 1-3 induced apoptosis of human epidermoid cancer cell (A431) in a dose-dependent manner.

Alternating isocratic and step gradient elution high-speed counter-current chromatography for the isolation of minor phenolics from Ormocarpum kirkii bark.

A total of 14 compounds were isolated from the ethanol bark extract of O. kirkii S. Moore (Fabaceae) by alternating isocratic and step gradient elution high-speed counter-current chromatography (HSCCC) methods, using several solvent systems with reference to the polarity of compounds being purified. The extract was successively fractionated with generic solvent systems including n-hexane-ethanol-water (4:2:2) and ethyl acetate-water (1:1). Resulting fractions were further purified using the following preparative gradient elution consisting of ethyl acetate-n-butanol-water (X:Y:10), (X:Y=9:1 (I); 8:2 (II); 7:3 (III); 6:4 (IV); 5:5 (V); 4:6 (VI) 3:7 (VII) and n-hexane- ethyl acetate-methanol-water (1:X:1:1), X=1, 2, 2.5, 3 solvent systems. Two flavone glycosides, apigenin-6-C-ß-d-glucopyranosyl-4'-O-[ß-d-glucopyranosyl-(1→5)]-ß-d-apiofuranoside (1) and apigenin-6-C-ß-d-glucopyranosyl-4'-O-ß-d-apiofuranoside (2), and one biflavanone diglycoside 7,7″-di-O-ß-d-glucosylliquiritigeninyl-(I-3,II-3)-naringenin (4) were isolated as new compounds along with other 11 known ones. The structures of the isolated compounds were identified by HPLC-UV, ESI-MS, 1D and 2D NMR and comparison with literature data. Thus, over common traditional chromatographic methods, the present study shows that HSCCC is a useful and fast method for natural product research with no losses and lower solvent use.