Sesamolinol glucoside, disaminyl ether, and other lignans from sesame seeds.

The application of a procedure based on XAD-4 adsorption resin permitted the obtainment of an enriched polyphenolic extract from Sesamum indicum seeds. Chemical analysis of the obtained extract led to the identification of 12 lignans. Among them, 2 lignans, (+)-sesamolinol-4'-O-ß-D-glucoside and disaminyl ether, are reported for the first time as natural compounds. Their structure has been determined by spectroscopic methods, mainly by the application of one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) techniques [heteronuclear multiple-quantum coherence (HMQC), heteronuclear multiple-bond correlation (HMBC), and nuclear Overhauser effect spectrometry (NOESY)] and mass spectroscopy. The isolated compounds were evaluated for their antimutagenic activity. Among the tested lignans, the most active lignan was found to be sesamolin, followed by sesamolinol and samin, against H(2)O(2). Additionally, some of the tested lignans showed desmutagenic activity against benzo[a]pyrene (BaP).

Development of an ion-pairing reversed-phase liquid chromatography method using a double detection analysis (UV and evaporative light scattering detection) to monitor the stability of Alimta(®)-pemetrexed preparations: identification and quantification of L-glutamic acid as a potential degradation product.

A new method based on high-performance liquid chromatography coupled to ultraviolet and evaporative light scattering detection (HPLC-UV-ELSD) was developed for the determination of L-glutamic acid, a potential degradation product of pemetrexed, and for the quantification of pemetrexed itself. This is an ion-pairing, reversed-phase method. The column was a Synergi MAX-RP C12 4 µm (150 mm x 4.6 mm). The mobile phase was 1 mM tridecafluoroheptanoic acid in aqueous solution and acetonitrile under gradient elution mode. L-Glutamic acid was detected by ELSD, and pemetrexed by UV at 254 nm. Good resolution was achieved between pemetrexed and L-glutamic acid. The HPLC method was validated according to SFSTP and ICH guidelines, and applied the accuracy profile procedure with a five-level validation experimental design. For pemetrexed, the decision criteria selected consisted of the acceptability limits (±3%) and the proportion of results within the calculated tolerance intervals (95%). In conclusion, the proposed analytical procedures were validated over the selected validation domains for L-glutamic acid (0.005-0.025 mg/mL) and pemetrexed (0.4-0.6 mg/mL) and shown to provide a very effective method.

Synthesis and kinase inhibitory activity of novel substituted indigoids.

The bis-indole indigoids are a promising protein kinase inhibitor scaffold to be further evaluated against the numerous human diseases that imply abnormal regulation of kinases including neurodegenerative disorders. In an effort to identify new pharmacological inhibitors of disease-relevant protein kinases with increased potency and selectivity, we designed, synthesized new 5,7-disubstituted or 6-substituted bis-indole derivatives. On the basis of our previous synthetic work, 22 selected compounds were tested on CDK1/cyclin B, CDK5/p25, DYRK1A, CK1, and GSK-3alpha/beta kinases, five kinases involved in Alzheimer's disease. Some of them were also evaluated for their cytotoxic and antiproliferative activities. 6-Nitro-3'-N-oxime-indirubin and 5-amino-3'-N-oxime-indirubin derivatives exhibited inhibitory activity in a submicromolar range against CDK1/cyclin B (0.18 and 0.1 microM, respectively), CK1 (0.6 microM and 0.13 microM) and GSK3 (0.04 microM and 0.36 microM).

One-pot synthesis of 5-phenylimino, 5-thieno or 5-oxo-1,2,3-dithiazoles and evaluation of their antimicrobial and antitumor activity.

We here report the synthesis and biological evaluation of rare 4-substituted-5-phenylimino, 5-thieno- and 5-oxo-1,2,3-dithiazoles. Dithiazoles were selectively obtained in moderate to high yields (25-73%) via a one-pot reaction from various ethanoneoximes with sulfur monochloride, pyridine in acetonitrile followed by treatment by corresponding nucleophiles (aniline, thioacetamide and formic acid). All the synthesized compounds were screened for their antibacterial (against bacteria Escherichia coli, Salmonellaenterica serovar Typhimurium, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus faecalis, Bacillus cereus and Listeria inocua), antifungal (against pathogenic strains Candida albicans, Candida glabrata, Candida tropicalis and Issatchenkia orientalis) and antitumor (on human cell lines MCF-7 and MDA-MB-231) activity. 4-(2-Pyridinyl)-5H-1,2,3-dithiazole-5-thione and 4-ethylcarboxyl-5H-1,2,3-dithiazole-5-thione (5d, 5h) that are active against Gram-positive bacteria are significantly active against fungi. 4-(2-Benzofuranyl)-5-phenylimino-5H-1,2,3-dithiazole (4e) exerts antiproliferative activity.