Lycium schweinfurthii: new secondary metabolites and their cytotoxic activities.

Two new compounds, 11S-methoxy-11,12-dihydro phytuberin (2) and 9S-methoxy-benzocyclononan-7-one (6), together with twenty-six known ones were isolated from Lycium schweinfurthii (Solanaceae). Their planar structure was established by extensive spectroscopic analyses. The absolute configuration of compound 6 was determined by time dependent density functional theory calculations (TDDFT). The cytotoxic potential of the isolates was assessed in cultured skin cancer (G-361) and colon cancer (HCT-116 and CaCo-2) cell lines. Certain flavonoids showed the highest cytotoxic activity, with IC50 values ranging from 7.1 to 63.3 µM; meanwhile 5-flurouracil showed IC50 values ranging from 62.4 to >100 µM. All compounds showed minimal toxicity towards normal cells from skin (NHDF-4) and colon (CCD-841), indicating their potential selectivity and safety as cytotoxic candidates.

Rho-kinase inhibitors from adlay seeds.

Rho-kinase enzymes are one of the most important targets recently identified in our bodies. Several lines of evidence indicate that these enzymes are involved in many diseases and cellular disorders. ROCK inhibitors may have clinical applications for cancer, hypertension, glaucoma, etc. Our study aims to identify the possible involvement of Rho-kinase inhibition to the multiple biological activities of adlay seeds and provide a rationale for their folkloric medicines. Hence, we evaluated Rho-kinase I and II inhibitory activity of the ethanol extract and 28 compounds derived from the seeds. A molecular docking assay was designed to estimate the binding affinity of the tested compounds with the target enzymes. The results of our study suggest a possible involvement of Rho-kinase inhibition to the multiple biological activities of the seeds. Furthermore, the results obtained with the tested compounds revealed some interesting skeletons as a scaffold for design and development of natural Rho-kinase inhibitors.

Melanogenesis inhibitors from Coix lacryma-jobi seeds in B16-F10 melanoma cells.

An adenine derivative, 9-ß-D-glucopyranosyl adenine, reported for the first time from a natural source, in addition to nine known compounds were isolated from the seeds of Coix lacryma-jobi. Their structures were elucidated based on extensive spectroscopic and chemical studies. The isolated compounds and the ethanol extract have been assayed for melanin inhibition using B16-F10 melanoma cell line. The results of our study suggested the potential use of Coix lacryma-jobi seeds as a skin whitening agent and reveal the seeds to be a rich source of important phytochemicals with melanogenesis inhibitory activity. Among the isolated compounds, coixol (2) and 2-O-ß-glucopyranosyl-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (8) exhibited potent melanogenesis inhibitory activity with no obvious melanocytotoxicity. The rest of the compounds showed weak to moderate activity.

Partial contribution of Rho-kinase inhibition to the bioactivity of Ganoderma lingzhi and its isolated compounds: insights on discovery of natural Rho-kinase inhibitors.

Recent studies identified Rho-kinase enzymes (ROCK-I and ROCK-II) as important targets that are involved in a variety of diseases. Synthetic Rho-kinase inhibitors have emerged as potential therapeutic agents to treat disorders such as hypertension, stroke, cancer, diabetes, glaucoma, etc. Our study is the first to screen the total ethanol extract of the medicinal mushroom Ganoderma lingzhi with thirty-five compounds for Rho-kinase inhibitory activity. Moreover, a molecular binding experiment was designed to investigate the binding affinity of the compounds at the active sites of Rho-kinase enzymes. The structure-activity relationship analysis was investigated. Our results suggest that the traditional uses of G. lingzhi might be in part due to the ROCK-I and ROCK-II inhibitory potential of this mushroom. Structure-activity relationship studies revealed some interesting features of the lanostane triterpenes that potentiate their Rho-kinase inhibition. These findings would be helpful for further studies on the design of Rho-kinase inhibitors from natural sources and open the door for contributions from other researchers for optimizing the development of natural Rho-kinase inhibitors.

Lucidumol C, a new cytotoxic lanostanoid triterpene from Ganoderma lingzhi against human cancer cells.

A new oxygenated lanostane-type triterpene, named lucidumol C, together with six known compounds, was isolated from the chloroform extract of the fruiting bodies of Ganoderma lingzhi. Structures were established based on extensive spectroscopic and chemical studies. Potential cytotoxic activities of the isolated compounds were evaluated against human colorectal carcinoma (HCT-116, Caco-2), human liver carcinoma (HepG2), and human cervical carcinoma (HeLa) cell lines using WST-1 reagent. Selectivity was evaluated using normal human fibroblast cells (TIG-1 and HF19). Among the compounds, lucidumol C showed potent selective cytotoxicity against HCT-116 cells with an IC50 value of 7.86 ± 4.56 µM and selectivity index (SI) >10 with remarkable cytotoxic activities against Caco-2, HepG2 and HeLa cell lines.

New erythroxane-type diterpenoids from Fagonia boveana (Hadidi) Hadidi & Graf.

The aerial parts of Fagonia boveana afforded two new erythroxane-type diterpenes, 3beta,15,16-trihydroxy-erythrox-4(18)-ene (2) and 15,16-dihydroxy-cis-ent-erythrox-3-ene (fagonene) (3) together with two known ones; 16-O-acetylfagonone (1) and 7beta-hydroxy fagonene (8). Also a new guaiane sesquiterpene alcohol, 6,10-epoxy-4alpha-hydroxy guaiane type sesquiterpene (4) has been isolated. In addition three 8-methoxy flavonols, 8-methoxy-quercetin-3,7,3'-trimethyl ether (ternatin) (5), gossypetin, 3,8,3',4' tetramethyl ether (6) and herbacetin-3,8-dimethyl ether (7) were also isolated. The structures of the isolated compounds have been determined on the basis of spectroscopic evidences as well as physical and chemical correlation with known compounds. On performing different assays for biological activities, 6 displayed significant cytotoxic activity against KA3IT and NIH3T3 cell lines, 8 was the most active antiviral against Herpes simplex type 1 while 7 was the most active cancer-preventive agent using protein-tyrosine kinase inhibitory method.

Cytotoxic hydroazulene diterpenes from the brown alga Dictyota dichotoma.

Two new hydroazulenoid (prenyl guaiane) diterpenes, dictyone acetate (2) and 3,4-epoxy 13-hydroxy pachydictyol A (4) were isolated from the petroleum ether fraction of the alcoholic extract of the brown alga, Dictyota dichotoma (Hudson) Lamouroux, which was collected from the Red Sea coasts at Hurgada, Egypt, together with three known ones, pachydictyol A (1), dictyone (3) and 11-hydroxypachydictyol A (dictyol E) (5). In addition, the steroidal compound, stigmasta-5,(E)-24(28)-dien-3-beta-ol (fucosterol) (6) was also isolated. The structures of the isolated compounds have been determined on the basis of spectroscopic evidences as well as physical and chemical correlation with known compounds. Compounds 1, 2, 3 and 5 showed moderate cytotoxic activity.