Quinones from Cordia species from 1972 to 2023: isolation, structural diversity and pharmacological activities.

Plants of the genus Cordia (Boraginaceae family) are widely distributed in the tropical regions of America, Africa, and Asia. They are extensively used in folk medicine due to their rich medicinal properties. This review presents a comprehensive analysis of the isolation, structure, biogenesis, and biological properties of quinones from Cordia species reported from 1972 to 2023. Meroterpenoids were identified as the major quinones in most Cordia species and are reported as a chemotaxonomic markers of the Cordia. In addition to this property, quinones are reported to display a wider and broader spectrum of activities, are efficient scaffold in biological activity, compared to other classes of compounds reported in Cordia, hence our focus on the study of quinones reported from Cordia species. About 70 types of quinones have been isolated, while others have been identified by phytochemical screening or gas chromatography. Although the biosynthesis of quinones from Cordia species is not yet fully understood, previous reports suggest that they may be derived from geranyl pyrophosphate and an aromatic precursor unit, followed by oxidative cyclization of the allylic methyl group. Studies have demonstrated that quinones from this genus exhibit antifungal, larvicidal, antileishmanial, anti-inflammatory, antibiofilm, antimycobacterial, antioxidant, antimalarial, neuroinhibitory, and hemolytic activities. In addition, they have been shown to exhibit remarkable cytotoxic effects against several cancer cell lines which is likely related to their ability to inhibit electron transport as well as oxidative phosphorylation, and generate reactive oxygen species (ROS). Their biological activities indicate potential utility in the development of new drugs, especially as active components in drug-carrier systems, against a broad spectrum of pathogens and ailments.

Heterophynone and methyl ester of Colic acid, two new compounds with antimicrobial activity from Cola heterophylla (Sterculiaceae).

The ethyl acetate fraction, the stem bark and the residual methanolic extracts from the leaves of Cola heterophylla (Sterculiaceae) led to the isolation of two new compounds: Heterophynone (1) and methyl ester of Colic acid (6), along with four known triterpenes: betulinic acid (2), oleanolic acid (3), ursolic acid (4) and chletric acid (5). Structures of compounds were established by different spectroscopic methods that included 1D and 2D NMR experiment. The antimicrobial activity of isolated compounds was evaluated against two yeasts, Candida Albicans NR 29456 and Candida Krusei 1415; and five Gram-positive bacterial, Salmonella enteric Serovar Muenchem, Salmonella enteric Serovar Thyphimurium, Staphylococcus aureus NR 46003, Staphylococcus aureus NR46374 and Pseudomonas aeruginosa HM 601). Among tested compounds, Heterophynone was found to be the most active with significant antimicrobial activity against Salmonella enteric Serovar Thyphimurium (MIC = 7.82 µg/mL and MBC = 62.5 µg/mL) and good activity against Candida Albicans NR 29456 (MIC = 62.5 µg/mL).

Two new flavones glycosides with antimicrobial activities from Clerodendrum formicarum Gürke (Lamiaceae).

Clerodendrum formicarum Gürke from the Lamiaceae family is a Cameroonian medicinal plant. The crude methanol, methanol residual and ethyl acetate extracts of leaves have been phytochemically studied using chromatography column to afford four compounds; two new flavones glycoside: clerodendronone 1a (3) and clerodendronone 1b (4) along with two known compounds: 5,7-dihydroxy-4'-methoxyflavone (1) and 5-hydroxy-7,4'-dimethoxyflavone (2). Compound structures have been elucidated on the basis of their spectroscopy data and with literature information. The anti-microbial activities of extracts and three isolated compounds were performed. The antibacterial activity was evaluated against four gram positive, five gram negative and three fungus. Clerodendronone 1b (4) showed good antibacterial activity against bacterial gram negative Shigella flexineri NR518 (MIC = 62.5 µg/ml) and moderate activity against Staphylococcus aureus NR46374 (MIC = 250 µ/ml). The ethyl acetate extract recorded good antibacterial activity against Staphylococcus aureus NR46003 (MIC = 125 µg/ml) and Staphylococcus aureus NR46374 (MIC = 125 µg/ml).

Bioactive constituents from seeds of Annona Senegalensis Persoon (Annonaceae).

Column chromatography led to the isolation and full characterization of N-cerotoyltryptamine (1) previously described in a mixture of 5 compounds, asimicin (2) and ent-19-Carbomethoxykauran-17-oic acid (3) isolated from this species for first time alongside stigmasterol glycoside (4) and lacceroic acid (5). The structures of the compounds were established by extensive EIMS, HRESIMS, 1 D and 2 D NMR studies. Compound 1 and the extract AS were more potent inhibitors of ROS with IC50 values of 2.7 ± 0.1 µg/mL and 8.7 ± 10.2 µg/mL respectively than Ibuprofen (11.2 ± 1.9 µg/mL) as a standard anti-inflammatory drug. Compound 2 showed high inhibition on nitric oxide (IC50 = 3.9 ± 0.2 µg/mL), almost 6 times more active than the standard compound L-NMMA (IC50 = 24.2 ± 0.8 µg/mL) used. Compounds showed relatively low toxicity on NIH-3T3 fibroblast cells compared to standard. The results indicate that compounds 1 and 2 are potent anti-inflammatory drug candidates.

Antifungal potential of extracts, fractions and compounds from Uvaria comperei (Annonaceae) and Oxyanthus unilocularis (Rubiaceae).

Phytochemical study of Uvaria comperei afforded an alkaloid, 8,9-dimethoxy-5H-phenanthridin-6-one (1), isolated and characterised (assignment of 1H and 13C NMR) for the first time from a natural source along with two flavonoids, (2S)-5-hydroxy-7,8-dimethoxyflavanone (2) and (2S)-7-hydroxy-5-methoxy-6,8-dimethylflavone (3). Clethric acid (4), oleanoic acid (5), ß-sitosterol 3-O-ß-D-glucopyranoside (9), ß-sitosterol palmitate (6) and a mixture of stigmasterol (7) and ß-sitosterol (8) were isolated from Oxyanthus unilocularis. The structures of these compounds were elucidated using modern spectroscopic techniques including1D and 2D Nuclear Magnetic Resonance (NMR) Spectroscopy (1H, 13C, 1H-1H COSY, HSQC, HMBC) and Mass Spectrometry. Some fractions and compounds from Uvaria comperei exhibited good antifungal activity against clinical isolates and standard strains of yeast species of Candida and Cryptococcus genera while extracts from Oxyanthus unilocularis displayed weak antifungal activity. The results obtained show that Uvaria comperei could be a potential source of antifungal drugs.

Cordidepsine is A Potential New Anti-HIV Depsidone from Cordia millenii, Baker.

Chemical investigation of Cordia millenii, Baker resulted in the isolation of a new depsidone, cordidepsine (1), along with twelve known compounds including cyclooctasulfur (2), lup-20(29)-en-3-triacontanoate (3), 1-(26-hydroxyhexacosanoyl)glycerol (4), glyceryl-1-hexacosanoate (5) betulinic acid (6), lupenone (7), ß-amyrone (8), lupeol (9), ß-amyrin (10), allantoin (11), 2'-(4-hydroxyphenyl)ethylpropanoate (12) and stigmasterol glycoside (13). Hemi-synthetic reactions were carried out on two isolated compounds (5 and 6) to afford two new derivatives, that is, cordicerol A (14) and cordicerol B (15), respectively. The chemical structures of all the compounds were established based on analysis and interpretation of spectroscopic data such as electron ionization mass spectrometry (EI-MS), high resolution electrospray ionization mass spectrometry (HR-ESI-MS), fast atom bombardment mass spectrometry (FAB-MS), one dimension and two dimension nuclear magnetic resonance (1D and 2D-NMR) spectral data as well as X-ray crystallography (XRC). Lupeol ester derivatives [Lup-20(29)-en-3-triacontanoate (3)], monoglycerol derivatives [1-(26-hydroxyhexacosanoyl)glycerol (4) and glyceryl-1 hexacosanoate (5)] were isolated for the first time from Cordia genus while sulfur allotrope [cyclooctasulfur (2)] was isolated for the first time from plant origin. Biological assays cordidepsine (1) exhibited significant anti-HIV integrase activity with IC50 = 4.65 µM; EtOAc extract of stem barks, EtOAc fraction of roots and leaves were not toxic against 3T3 cells.

Regulation of CD1, Ki-67, PCNA mRNA expression, and Akt activation in estrogen-responsive human breast adenocarcinoma cell line, MCF-7 cells, by griffonianone C, an isoflavone derived from Millettia griffoniana.

CONTEXT: Millettia griffoniana Baill. (Fabaceae), which contains isoflavonoids like griffonianone C (Griff C), is commonly used in the folk medicine in Cameroon to treat various ailments. Possible health benefits of Griff C which include alleviation of menopausal symptoms, limitation of bone resorption, and lowering of the risks of cancer and cardiovascular diseases attracted our interest. OBJECTIVE: The effects of Griff C on the regulation of the expression of proliferation markers such as proliferating cell nuclear antigen (PCNA), cyclin D1 (CD1) and Ki-67 are investigated here. Its role in apoptosis or cell survival, through the phosphatidylinositol 3 kinase-Akt (PI3K-Akt) signaling pathway is further studied. MATERIALS AND METHODS: Semiquantitative real-time PCR was performed to analyze the effects of Griff C on gene expression in MCF-7 cells. Western blot analysis was used to assess the role of Griff C on the expression of phosphorylated Akt in MCF-7 cells. RESULTS: Griff C induced a 4.84-fold increase in the expression of Ki-67 mRNA at the concentration of 10(-8) M and a 3.90-fold increase of CD1 mRNA at 10(-7) M. Griff C slightly increased the phosphorylation of Akt at its serine 473 residue. Akt phosphorylation was inhibited by the PI3K inhibitor, LY294002, but not by the specific estrogen receptor antagonist, fulvestrant. DISCUSSION AND CONCLUSION: These findings suggest that Griff C can modulate proliferation of MCF-7 cells. Our results also suggest that Griff C can affect the PI3K-related signaling pathway. Thus, Griff C may exert part of its low proliferative and antiapoptotic effects by a nongenomic mode of action.

Modulation of some estrogen-responsive genes in the vena cava of ovariectomised Wistar rats by griffonianone C, an isoflavone derived from Millettia griffoniana Baill. (Fabaceae).

In the present study, we investigated whether griffonianone C (Griff C), extracted from root bark of Millettia griffoniana, changes the expression of several estrogen-responsive genes in the vena cava of ovariectomised rats. For this purpose, we subcutaneously administered Griff C (2, 10, or 20mg/kg/d BW), 17ß-estradiol (E2: 10µg/kg/d BW) as positive control, and a vehicle control respectively for three days. Relative expression levels of estrogen receptor α (ERα), progesterone receptor (PR), cyclooxygenase2 (Cox-2), vascular endothelial growth factor (VEGF), VEGF-receptor 2, angiotensin converting enzyme (ACE), endothelial NO synthase (eNOS), proliferating cell nuclear antigen (PCNA) and Ki67 mRNA extracted from the vena cava of these rats were quantified by real-time PCR. Results showed that Griff C up-regulated the expression of PR, ACE, ERα, VEGF, VEGFR2 and Ki67. However, the results of Cox-2, PCNA, and eNOS expression did not reach significance in the E2 and Griff C treated samples. These results show that griffonianone C regulated a few of the analysed genes in a similar fashion than estradiol; however, others showed a different pattern. This suggests that some of the biological effects attributed to M. griffoniana are mediated via ER pathway others may be mediated via other pathways.