Bioactive cholinesterase inhibitions of clerodanes from the flowers of Croton krabas and molecular docking studies.

The first investigation of the phytochemical profile of the flowers of Croton krabas led to the isolation of two new clerodane diterpenes, 6S-crotocaudin (1) and crotocaudin B (2), together with two known clerodanes, 6S-crotoeurin C (3) and isoteucvin (4). The structures and absolute configurations of isolated clerodanes were elucidated by extensive analysis of NMR spectroscopic data, mass spectrometry and ECD calculations. Compounds 1-4 demonstrated significant inhibitory activity towards acetylcholinesterase (AChE). Notably, compound 2 exhibited the strongest AChE inhibition (IC50 1.01 µM). Compounds 3 and 4 showed potent butyrylcholinesterase (BChE) inhibitory activity with IC50 values of 1.09 and 1.12 µM, respectively. The molecular docking results revealed that 2 bound to the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE, while 3 occupied in the CAS of BChE.

A new feruloylfriedelinol from the stems of Bridelia stipularis and its α-glucosidase inhibition.

Phytochemical investigation of the stems of Bridelia stipularis led to the isolation of a new triterpene, 3ß-O-trans-feruloylfriedelinol (1), together with five known compounds, friedelin (2), 3ß-friedelinol (3), lupeol (4), stigmasterol (5), and 4-(1,5-dimethyl-3-oxo-4-hexenyl)benzoic acid (6). Their structures were identified by intensive spectroscopic analysis including 1D and 2D nuclear magnetic resonance, infrared, and mass spectrometry. Compound 1 showed significant α-glucosidase inhibitory activity (IC50 = 337.49 ± 0.59 µM) close to the standard, acarbose. Furthermore, the structure activity relationship of 1 was analyzed by molecular docking studies. In addition, the molecular docking results showed that the interaction between 1 and the active site occurred through hydrophobic forces and hydrogen bonds.

Four New Anthraquinones with Histone Deacetylase Inhibitory Activity from Ventilago denticulata Roots.

Chromatographic separation of the crude extracts from the roots of Ventilago denticulata led to the isolation of four new anthraquinones, ventilanones L-O (1-4), together with eight known anthraquinones (5-12). Their structures were elucidated by spectroscopic methods (UV, IR, 1H NMR, 13C NMR, and 2D NMR) and mass spectrometry (MS), as well as comparison of their spectroscopic data with those reported in the literature. HDACs inhibitory activity evaluation resulted that compound 2 exhibited moderate antiproliferative activity against HeLa and A549 cell lines but nontoxic to normal cell. Molecular docking indicated the phenolic functionality of 2 plays crucial interactions with class II HDAC4 enzyme.

Phytochemicals from twigs of Afzelia xylocarpa and their antioxidation kinetics of oxymyoglobin.

The phytochemical investigation of crude n-hexane and ethyl acetate extracts from twigs of Afzelia xylocarpa (Kurz) led to the isolation of 14 known compounds. Their structures were elucidated by spectroscopic techniques (IR, 1H NMR, 13C NMR, and 2D NMR) as well as mass spectrometry. These structures were characterized as ß-sitosterol (1), lupeol (2), vanilic acid (3), 5,7-dihydroxychromone (4), (+)-mellein (5), isoliquiritigenin (6), 7-hydroxyemodin (7), physion (8), aromadendrin (9), naringenin (10), apigenin (11), luteolin (12), chrysoeriol (13) and kaempferol (14). Compounds 4-7 and 12-13 were isolated from the genus Afzelia for the first time. The selected compounds 5, 8, 9 and 12 exhibited potent activity for antioxidation kinetics of oxymyoglobin.

A New Apotirucallane from Walsura trichostemon Leaves and Its Antibacterial and α-Glucosidase Inhibitory Activities.

Phytochemical investigation of Walsura trichostemon leaves led to the isolation of a new apotirucallane-type triterpenoid, 11,25-dideacetyl-16-hydroxytrichostemonate (1), along with two known apotirucallane-type triterpenoids (2 and 3), two known tirucallane-type triterpenes (4 and 5), and two known steroids (6 and 7). Their structures were identified by intensive analysis of 1D and 2D nuclear magnetic resonance, infrared, and mass spectrometry data, which were compared with data reported in the literature. Compounds 2, 3, and 5 exhibited moderate antibacterial activity against Pseudomonas aeruginosa (minimum inhibitory concentration (MIC) value: 64 µg/mL), and compound 4 showed weak antibacterial activity against P. aeruginosa (MIC: 128 µg/mL). Furthermore, compound 5 displayed activity against Bacillus cereus (MIC: 64 µg/mL). In addition, compound 4 showed stronger α-glucosidase inhibitory activity than the control, acarbose. The active compound 4 was subjected to molecular docking experiments using AutoDock4 and revealed precise interactions with the active gorge of the enzyme through hydrogen bonding, supporting the in vitro results.

ent-Clerodane diterpenoids from the stems of Croton krabas.

The first phytochemical investigation from the stems of Croton krabas resulted in the isolation of three new ent-clerodane diterpenoids, crotonkrabases A-C (1-3), along with two known compounds, 12-oxohardwickiic acid (4) and crotonpyrone B (5). Their structures were elucidated using extensive spectroscopic methods. The structure of 3 was unambiguously proven by X-ray crystallography. Furthermore, the absolute configurations of compounds 1-3 were identified by NOESY and the comparison of their experimental ECD spectra with those of calculated ECD spectra reported in the literature. Compounds 1, 2, and 5 showed antibacterial activities against two Gram-positive bacteria (Bacillus cereus and Bacillus subtilis); whereas compound 4 exhibited weak antibacterial against B. cereus. In addition, compound 4 showed potent α-glucosidase inhibitory activity, which was lower than the reference standard acarbose.

Terpenoids from the root bark of Pterolobium macropterum.

Five new compounds, including pteroloterins A-C (1, 3, and 4), 1ß-acetoxytaepeenin C (2), and 8aα-hydroxycadinenal (5), and 11 known compounds were isolated from the root bark of Pterolobium macropterum. All compounds were evaluated for cytotoxicity against the cholangiocarcinoma cell lines. Compound 9 showed weak cytotoxicity against the KKU-M139 cell line with an IC50 value of 23.24 ± 0.18 µM and showed no activity against normal cells.

Cytotoxic aporphine alkaloids from leaves and twigs of Pseuduvaria trimera (Craib).

From ethyl acetate-methanol extracts of leaves and twigs of Pseuduvaria trimera a new aporphine alkaloid; 8-hydroxy-1,4,5-trimethoxy-7-oxoaporphine or 8-hydroxyartabonatine C (1) was isolated, together with the known 1,2,3-trimethoxy-4,5-dioxo-6a,7-dehydroaporphine (ouregidione, 2). Their structures were elucidated by a combination of spectral methods; mainly 2D NMR; IR and MS. Compounds 1 and 2 exhibited cytotoxic activity with IC50 values of 26.36±5.18 µM and 12.88±2.49 µM, respectively, for human hepatocellular carcinoma HepG2 cells, and 64.75±4.45 and 67.06±3.5 µM, respectively, for human breast cancer MDA-MB231 cells. Both compounds displayed anti-cancer activity but less than that of doxorubicin; a conventional chemotherapeutic drug, the IC50 levels of which were 2.21±1.72 and 1.83±0.09 µM for HepG2 and MDA-MB231 cells, respectively.

Cyclin-dependent kinases 5 template: useful for virtual screening.

The present study reports the development of a template for the active binding site of Cdk5 for structure-based drug design. The developed template of Cdk5 was validated by redocking with ligands I (PBD code 1UNG), II (PBD code 1UNL) and III (PBD code 1UNH). The results demonstrate a good match of the docked and the crystallographic binding orientations with RMSD less than 2.0Å. The validation results show that the constructed Cdk5 template is a good model system for predicting ligand binding orientations and binding affinities. Furthermore, the developed template was applied to predict binding mode and binding affinity of thirty-six known Cdk5 inhibitors. The results showed that the binding energy of almost Cdk5 inhibitors related to their biological evaluation.

Cytotoxicity against cholangiocarcinoma cell lines of zerumbone derivatives.

Cholangiocarcinoma (CCA) is an aggressive malignancy with a very high morbidity and mortality for which an effective treatment is lacking. In this study, seventeen zerumbone derivatives were synthesized and evaluated for in vitro cytotoxicity against cholangiocarcinoma cell lines. 5 showed the most potent antiproliferative activity against KKU-100 cell line with an IC(50) value of 16.44 microM. To investigate the potential molecular target of the most active compound, the docking was performed using different enzymes and receptor proteins including CDK-2, CDK-5, EGFR, and GSK-3. The docking results revealed that 5 exhibited better binding interaction to EGFR than CDK-2, CDK-5 and GSK-3. All results indicate that 5 should be a promising candidate for treatment of cancer.

Structural modification of 5,7-dimethoxyflavone from Kaempferia parviflora and biological activities.

5,7-Dimethoxyflavone, a major compound from Kaempferia parviflora, was used as a starting material for structural modification. Seven flavonoid derivatives have been synthesized from this flavone. Two new oxime derivatives 4 and 6 exhibited cytotoxicity against HepG2 cell line with IC50 values of 36.38 and 25.34 microg/mL, respectively, and against T47D cell line with IC50 values of 41.66 and 22.94 microg/mL, respectively. Compound 7 showed cytotoxicity against HepG2 and T47D cell lines with IC50 values of 21.36 and 25.00 microg/mL, respectively. Compounds 6 and 7 showed cytotoxicity nearly equal to the tamoxifen standard. In addition, oxime 6 exhibited antifungal activity against Candida albicans with an IC50 value of 48.98 microg/mL.

Bioactive constituents from the stems of Dalbergia parviflora.

From the stems of Dalbergia parviflora, three known flavonoids, six known isoflavonoids, a new isoflavone, dalparvone (2) and a new cinnamyl derivative, dalparvinene (6) were isolated and characterized. Isoflavan 3 exhibited strong cytotoxicity against KB and NCI-H187 cell lines with IC(50) values of 0.53 and 2.04 microg/ml, respectively. Compound 6 demonstrated strong cytotoxicity against NCI-H187 with an IC(50) value of 1.46 microg/ml. Compounds 4 and 6 possessed moderate cytotoxicity against KB cells with IC(50) values of 6.78 and 9.89 microg/ml, respectively. In addition, 2 exhibited moderate antiplasmodial activity with an IC(50) value of 8.19 microg/ml.