Isomeric exocyclic and endocyclic dienolates: behavior towards electrophiles

Isomeric exocyclic and endocyclic dienolates 5 and 6 were generated and while 6 reacted with electrophiles exclusively at the α -position the regiospecificity of 5 was found to be dependent on the type of electrophile employed.     

Acridone Derivatives from Atalantia monophyla Inhibited Cancer Cell Proliferation through ERK Pathway

The present study aimed to investigate the effect of acridone alkaloids on cancer cell lines and elucidate the underlying molecular mechanisms. The ten acridone alkaloids from Atalantia monophyla were screened for cytotoxicity against LNCaP cell lines by a WST-8 assay. Then, the most potential acridone, buxifoliadine E, was evaluated on four types of cancer cells, namely prostate cancer (LNCaP), neuroblastoma (SH SY5Y), hepatoblastoma (HepG2), and colorectal cancer (HT29). The results showed that buxifoliadine E was able to significantly inhibit the proliferation of all four types of cancer cells, having the most potent cytotoxicity against the HepG2 cell line. Western blotting analysis was performed to assess the expression of signaling proteins in the cancer cells. In HepG2 cells, buxifoliadine E induced changes in the levels of Bid as well as cleaved caspase-3 and Bax through MAPKs, including Erk and p38. Moreover, the binding interaction between buxifoliadine E and Erk was investigated by using the Autodock 4.2.6 and Discovery Studio programs. The result showed that buxifoliadine E bound at the ATP-binding site, located at the interface between the N- and C-terminal lobes of Erk2. The results of this study indicate that buxifoliadine E suppressed cancer cell proliferation by inhibiting the Erk pathway.     

Synthesis of bioreductive esters from fungal compounds

Four new bioreductive esters (7-10) have been synthesized. Their structures composed of trimethyl lock containing quinone propionic acid with an ester linkage to the fungal cytotoxic compounds; preussomerin G (1), preussomerin I (2), phaseolinone (3) and phomenone (4). The synthesized esters are aimed to act via reductive activation specifically at the cancer cells, resulting from hypoxia and overexpression of reductases. Hence, the toxicity will be lessened during distribution across the normal cells. The anticancer activity was determined in cancer cell lines with reported reductase i.e., BC-1 cells and NCI-H187 as well as in non-reductase containing cancer cells; KB cells. When considering each cell lines, result showed that structure modification giving to 7-10 led to less cytotoxicity than their parent compounds (1-4). Both 7 and 8 were strongly cytotoxic (IC50 < or = 5 microg/ml) to NCI-H187, whereas 9 and 10 were moderately cytotoxic (IC50 = 6-10 microg/ml) to BC-1 cells. Additional study of stability of represented phenolic ester (8) and an alcoholic ester (9) were performed. Result illustrated that both 8 and 9 were stable in the presence of esterase. Therefore, the cytotoxicity of the synthesized compounds (8-10) might be due to partial bioreductive activation in the cancer cells.     

Histone Deacetylase Inhibitory Activity and Antiproliferative Potential of New [6]-Shogaol Derivatives

Twenty newly synthesized derivatives of [6]-shogaol (4) were tested for inhibitory activity against histone deacetylases. All derivatives showed moderate to good histone deacetylase inhibition at 100 µM with a slightly lower potency than the lead compound. Most potent inhibitors among the derivatives were the pyrazole products, 5j and 5k, and the Michael adduct with pyridine 4c and benzothiazole 4d, with IC₅₀ values of 51, 65, 61 and 60 µM, respectively. They were further evaluated for isoform selectivity via a molecular docking study. Compound 4d showed the best selectivity towards HDAC3, whereas compound 5k showed the best selectivity towards HDAC2. The potential derivatives were tested on five cancer cell lines, including human cervical cancer (HeLa), human colon cancer (HCT116), human breast adenocarcinoma cancer (MCF-7), and cholangiocarcinoma (KKU100 and KKU-M213B) cells with MTT-based assay. The most active histone deacetylase inhibitor 5j exhibited the best antiproliferative activity against HeLa, HCT116, and MCF-7, with IC₅₀ values of 8.09, 9.65 and 11.57 µM, respectively, and a selective binding to HDAC1 based on molecular docking experiments. The results suggest that these compounds can be putative candidates for the development of anticancer drugs via inhibiting HDACs.     

Simultaneous identification and quantitation of 11 flavonoid constituents in Kaempferia parviflora by gas chromatography

Kaempferia parviflora (Krachaidum; KD) is a Thai herb, the rhizomes of which have been used in folk medicine and ritual ceremonies. The increasing use of KD has led to concerns regarding the variation of quality, potency and efficacy of KD products. A gas chromatographic method was developed and validated using 11 flavonoids that had been fully characterized as reference. Limits of detection ranged from a low of 0.1 ppm to a high of 1.0 ppm. The limits of quantitation were a low of 0.5 ppm (5-hydroxy-3,7-dimethoxyflavone) to a high of 3.0 ppm (5,7,4'-trimethoxyflavone and 5,7,3',4'-tetramethoxyflavone). Precision of intra- and inter-day analyses gave a RSD range of 3.02-8.25 and 2.84-12.37, respectively. The diversity of flavonoid content and their distribution profiles in KD samples from 12 different origins was investigated using the validated method. Total flavonoid content in these samples ranged from 23.86 to 60.98 mg/g. Two of the compounds, 5,7-dimethoxyflavone and 5,7,4'-trimethoxyflavone, emerged as major constituents. Samples contained as much as 21.68 and 9.88 mg/g, respectively. Two distinct patterns of the distribution of the flavonoids, as characterized by the ratio of these two compounds in the KD rhizome samples, were observed. This method is expected to be useful in the quantitative and qualitative analyses of the flavonoid content of KD samples and as a quality control assessment of KD raw materials and products.     

Different C-glycosidation products of glucal with alkynyl or propargyl silanes under acidic conditions

Propargylic and acetylenic silyl groups on propyne control the C-glycosidation products depending on the trimethylsilyl and triisopropylsilyl groups used. Some mechanistic discussions are included. [reaction: see text]