In Vitro and In Silico Evaluation of Anticholinesterase and Antidiabetic Effects of Furanolabdanes and Other Constituents from Graptophyllum pictum (Linn.) Griffith.

Graptophyllum pictum is a tropical plant noticeable for its variegated leaves and exploited for various medicinal purposes. In this study, seven compounds, including three furanolabdane diterpenoids, i.e., Hypopurin E, Hypopurin A and Hypopurin B, as well as with Lupeol, ß-sitosterol 3-O-ß-d-glucopyranoside, stigmasterol 3-O-ß-d-glucopyranoside and a mixture of ß-sitosterol and stigmasterol, were isolated from G. pictum, and their structures were deduced from ESI-TOF-MS, HR-ESI-TOF-MS, 1D and 2D NMR experiments. The compounds were evaluated for their anticholinesterase activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BchE), as well as their antidiabetic potential through inhibition of α-glucosidase and α-amylase. For AChE inhibition, no sample had IC50 within tested concentrations, though the most potent was Hypopurin A, which had a percentage inhibition of 40.18 ± 0.75%, compared to 85.91 ± 0.58% for galantamine, at 100 µg/mL. BChE was more susceptible to the leaves extract (IC50 = 58.21 ± 0.65 µg/mL), stem extract (IC50 = 67.05 ± 0.82 µg/mL), Hypopurin A (IC50 = 58.00 ± 0.90 µg/mL), Hypopurin B (IC50 = 67.05 ± 0.92 µg/mL) and Hypopurin E (IC50 = 86.90 ± 0.76 µg/mL). In the antidiabetic assay, the furanolabdane diterpenoids, lupeol and the extracts had moderate to good activities. Against α-glucosidase, lupeol, Hypopurin E, Hypopurin A and Hypopurin B had appreciable activities but the leaves (IC50 = 48.90 ± 0.17 µg/mL) and stem (IC50 = 45.61 ± 0.56 µg/mL) extracts were more active than the pure compounds. In the α-amylase assay, stem extract (IC50 = 64.47 ± 0.78 µg/mL), Hypopurin A (IC50 = 60.68 ± 0.55 µg/mL) and Hypopurin B (IC50 = 69.51 ± 1.30 µg/mL) had moderate activities compared to the standard acarbose (IC50 = 32.25 ± 0.36 µg/mL). Molecular docking was performed to determine the binding modes and free binding energies of Hypopurin E, Hypopurin A and Hypopurin B in relation to the enzymes and decipher the structure-activity relationship. The results indicated that G. pictum and its compounds could, in general, be used in the development of therapies for Alzheimer's disease and diabetes.

A new isoquinoline and ceramide from the stem barks of Discoglypremna caloneura (Pax) Prain (Euphorbiaceae) with antiproteinase and cytotoxic activities.

Two new compounds, an isoquinoline (1) and caloneuramide (2), a ceramide were isolated from the stem bark of Discoglypremna caloneura together with seven known compounds namely aurantiamide acetate (3), acetylaleuritolic acid (4), 3α-hydroxylaleuritolic acid 2α-p-hydroxybenzoate (5), mixture of stigmasterol (6) and ß-sitosterol (7), mixture of 7-oxo-stigmasterol (8) and 7-oxo-ß-sitosterol (9). Their structures were determined based on data from literature and spectroscopic methods. Derivatization reactions on the isoquinoline led to two new compounds, the methylated (10) and acetylated (11) derivatives. Some compounds and extracts were evaluated for their cytotoxic and antiproteinase activity. Antiproteinase effect of compounds 1, 10 and 11 exhibited IC50 values of 10.77, 1.19 and 3.61 µg/mL respectively; significantly low compared to the standard drug, acetyl salicylic acid (IC50 = 20.28 µg/mL). Ethyl acetate and methanol extract exhibited moderate cytotoxicity activity on Chang liver cells with CC50 values of 167.90 ± 2.20 and 106.30 ± 2.03 µg/mL compared to the reference drug cucurmin (CC50 = 11.05 ± 1.04 µg/mL).

Glycosides of polygalacic acid from the stem barks of Piper guineense Schum and Thonn.

In a continuation of our study on constituents of P. guineense now focusing on the search for saponins, phytochemical investigation of the n-BuOH fraction of P. guineense stem bark led to the isolation of three previously undescribed triterpenoid saponins, named guineenosides A─C (1─3). 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-{α-l-rhamnopyranosyl-(1 â†’ 3)-ß-d-xylopyranosyl-(1 â†’ 2)-α-l-arabinopyranosyl-(1 â†’ 4)-α-l-rhamnopyranosyl-(1 â†’ 3)-[α-l-arabinofuranosyl-(1 â†’ 4)]-α-l-rhamnopyranosyl-(1 â†’ 3)-ß-d-fucopyranosyl} polygalacic acid 28-O-α-l-rhamnopyranosyl-(1 â†’ 4)-α-l-rhamnopyranosyl-(1 â†’ 3)-ß-d-xylopyranosyl ester (1), 3-O-{α-l-rhamnopyranosyl-(1 â†’ 3)-ß-d-xylopyranosyl-(1 â†’ 2)-α-l-arabinopyranosyl-(1 â†’ 4)-α-l-rhamnopyranosyl-(1 â†’ 3)-[α-l-arabinofuranosyl-(1 â†’ 4)]-α-l-rhamnopyranosyl-(1 â†’ 3)-ß-d-fucopyranosyl} polygalacic acid 28-O-ß-d-glucopyranosyl-(1 â†’ 3)-α-l-rhamnopyranosyl-(1 â†’ 4)-α-l-rhamnopyranosyl-(1 â†’ 3)-ß-d-xylopyranosyl ester (2), and 3-O-{α-l-rhamnopyranosyl-(1 â†’ 2)-ß-d-xylopyranosyl-(1 â†’ 3)-ß-d-fucopyranosyl} polygalacic acid 28-O-[α-l-rhamnopyranosyl-(1 â†’ 4)-α-l-rhamnopyranosyl-(1 â†’ 3)-ß-d-xylopyranosyl ester (3). This is the first report of triterpenoid saponins from P. guineense.

Nitrile glucosides and serotobenine from Campylospermum glaucum and Ouratea turnarea.

Two nitrile glucosides (1S,3S,4S,5R)-4-benzoyloxy-2-cyanomethylene-3,5-dihydroxycyclohexyl-1-O-beta-glucopyranoside (campyloside A) and (1S,3S,4S,5R)-5-benzoyloxy-2-cyanomethylene-3-hydroxy-4-(2-pyrrolcarboxyloxy)cyclohexyl-1-O-beta-glucopyranoside (campyloside B) were isolated from the stem roots of Campylospermum glaucum, whereas serotobenine was isolated from Ouratea turnarea. The structure elucidations were based on spectroscopic evidence. The biological assays of compounds and crude extract of plant species showed good antimicrobial activity of crude extracts against Gram-positive cocci.

Antimicrobial biflavonoids from the aerial parts of Ouratea sulcata.

Investigation of the aerial parts of Ouratea sulcata led to the isolation of a biflavonoid named sulcatone A, together with the known compounds, 3-hydroxy-2,3-dihydroapigenyl-[I-4',O,II-3']-dihydrokaempferol, amentoflavone, lophirone A, agathisflavone, stigmasterol and stigmasteryl-3-O-beta-D-glucopyranoside. The structure of the compound was assigned as apigenyl-[I-4',O,II-3']-dihydrokaempferol, by means of spectroscopic analysis. Sulcatone A and 3-hydroxy-2,3-dihydroapigenyl-[I-4',O,II-3']-dihydrokaempferol exhibited significant in vitro antimicrobial activities against a range of microorganisms.