Johnson Foyere Ayafor

Vernoguinosterol and vernoguinoside, trypanocidal stigmastane derivatives from Vernonia guineensis (Asteraceae).

Two bitter stigmastane derivatives, vernoguinosterol (1) and vernoguinoside (2), have been isolated from the stem bark of Vernonia guineensis and their structures eludicated using spectroscopic methods. The new compounds exhibit trypanocidal activity.

SCREENING OF SOME AFRICAN MEDICINAL PLANTS FOR ANTIULCEROGENIC ACTIVITY: PART 1

Aqueous extracts of six plant species used in Cameroonian ethnomedicine for the relief of stomach complaints were tested for antiulcer activity. An HCl/EtOH solution was used to induce gastric lesions in male Wistar rats (140–190 g). The extracts of Voacanga africana, Eremomastax speciosa, Emilia praetermissa, Spilanthes filicaulis and Centella asiatica produced complete mucosal cytoprotection at a dose of 1000, 190, 500, 2000 and 500 mg/kg respectively. The extract of Clerodendrum splendens (500, 750, 1000 mg/kg) showed significant (p <0.01) dose‐dependent cytoprotection (50%–75%) compared with the controls. A combination of C. asiastica and S. filicaulis (1:1) (250–500 mg/kg) did not reveal the therapeutic advantage of combining both plant extracts in the clinical management of stomach ulcers.

A novel natural product compound enhances cAMP-regulated chloride conductance of cells expressing CFTRΔf508

BackgroundCystic fibrosis (CF) results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a chloride channel localized at the plasma membrane of diverse epithelia. The most common mutation leading to CF, ΔF508, occurs in the first nucleotide-binding domain (NBD1) of CFTR. The ΔF508 mutation disrupts protein processing, leading to a decreased level of mutant channels at the plasma membrane and reduced transepithelial chloride permeability. Partial correction of the ΔF508 molecular defect in vitro is achieved by incubation of cells with several classes of chemical chaperones, indicating that further investigation of novel small molecules is warranted as a means for producing new therapies for CF.Materials and MethodsThe yeast two-hybrid assay was used to study the effect of CF-causing mutations on the ability of NBD1 to self-associate and form dimers. A yeast strain demonstrating defective growth as a result of impaired NBD1 dimerization due to ΔF508 was used as a drug discovery bioassay for the identification of plant natural product compounds restoring mutant NBD1 interaction. Active compounds were purified and the chemical structures determined. The purified compounds were tested in epithelial cells expressing CFTRΔF508 and the resulting effect on transepithelial chloride permeability was assessed using short-circuit chloride current measurements.ResultsWild-type NBD1 of CFTR forms homodimers in a yeast two-hybrid assay. CF-causing mutations within NBD1 that result in defective processing of CFTR (ΔF508, ΔI507, and S549R) disrupted NBD1 interaction in yeast. In contrast, a CF-causing mutation that does not impair CFTR processing (G551D) had no effect on NBD1 dimerization. Using the yeast-based assay, we identified a novel limonoid compound (TS3) that corrected the ΔF508 NBD1 dimerization defect in yeast and also increased the chloride permeability of Fisher Rat Thyroid (FRT) cells stably expressing CFTRΔF508.ConclusionThe establishment of a phenotype for the ΔF508 mutation in the yeast two-hybrid system yielded a simple assay for the identification of small molecules that interact with the mutant NBD1 and restore dimerization. The natural product compound identified using the system (TS3) was found to increase chloride conductance in epithelial cells to an extent comparable to genistein, a known CFTR activator. The yeast system will thus be useful for further identification of compounds with potential for CF drug therapy.

Diarylheptanoids from Myrica arborea

Investigations of the stem and root bark of Myrica arborea (Myricaceae) have yielded two novel diarylheptanoids, myricarborin and 11-O-beta-D-xylopyranosylmyricanol along with the known myricanol and 5-O-beta-D-glucopyranosylmyricanol. The structures of the novel compounds were determined by spectroscopic methods.

Geranylated flavonoids from Dorstenia poinsettifolia

Abstract Two new geranylated flavonoids, poinsettifolins A and B, were isolated from the extracts of the herb Dorstenia poinsettifolia , and the structures were determined with NMR spectroscopy and mass spectrometry. In addition, the flavone 5,7,4-trihydroxy-8-prenylflavone (licoflavone C), the chalcones 4,2′,4′-trihydroxy-3′-prenylchalcone (isobavachalcone) and isobavachromene, the triterpene butyrospermol, and the carotenoid lutein were isolated.

Geranyl coumarins from Clausena anisata

Abstract Two new geranyl coumarins have been isolated from the leaves of Clausena anisata and identified as anisocoumarins I and J on the basis of spectral data and chemical correlation. The isolation of 21 coumarins from the leaves, stem-bark and roots of this plant and their biogenesis is also discussed.

Hoslundin, hoslundal, and hoslunddiol: three new flavonoids from the twigs of Hoslundia opposita (Lamiaceae)

Abstract Three new flavonoids (hoslundin 1 , hoslundal 4 , and hoslunddiol 6 ) have been isolated from the twigs of Hoslundia opposita . The structure of hoslundin has been determined mainly by the use of 2D n.m.r. long-range δ C /δ H correlation in conjunction with the ID proton-coupled 13 C n.m.r. spectrum, while the structures of the rest were established using 1 H and 13 C n.m.r. spectroscopy. The manner in which 2D n.m.r. long-range δ C /δ H H correlation experiments are used for determining bond connectivity during the process of structural elucidation is discussed.

Pachypophyllin and pachypostaudins A and B: three Bisnorlignans from Pachypodanthium staudtii

Abstract Three new bisnor lignans, pachypophyllin, pachypostaudin-A and pachypostaudin-B have been isolated from the bark of Pachypodanthium staudtii and their structures have been determined by 1 H and 13 CNMR spectroscopy and chemical correlations. 2,4,5-Trimethoxystyrene, probably a precursor of the bisnor lignans, was also isolated from the extracts. Furthermore, the potent antiviral flavonol, pachypodol, was obtained in significant amount.

Diterpenoids from Neoboutonia glabrescens (Euphorbiaceae).

Glabrescin, a daphnane diterpenoid, neoboutonin, a degraded diterpenoid with a novel skeleton, and neoglabrescins A and B, two rhamnofolane derivatives, have been isolated from the stem bark of Neoboutonia glabrescens Prain (Euphorbiaceae), together with the known tigliane derivative, baliospermin, and the known daphnane, montanin. Other constituents include squalene, 3-acetylaleuritolic acid, oleanolic acid and sitosterol, and the phenolic compounds 9-methoxy-1,7-dimethylphenanthrene and 2,3,8-tri-O-methylellagic acid. The structures were assigned on the basis of spectral studies and comparison with published literature data. The structures of neoglabrescins A and B were derived for their acetylated derivatives and, in the case of neoglabrescin A, confirmed by X-ray crystallographic analysis.

Cyclodione, an unsymmetrical dimeric diterpene from Cylicodiscus gabunensis

Abstract The structure of cyclodione ( 4 ) isolated from the stem bark of the tree Cylicodiscus gabunensis has been determined by spectroscopic methods. Cyclodione ( 4 ) is a nonacyclic dimeric cassane-type diterpenoid.