Acta Pharmacol Sin. 2009 Sep; 30(9): 1359-68Zhou YB, Feng X, Wang LN, Du JQ, Zhou YY, Yu HP, Zang Y, Li JY, Li JAIM: To discover novel cell division cycle 25 (CDC25) B inhibitors and elucidate the mechanisms of inhibition in cancer cells. METHODS: Cell growth inhibition was detected by MTT assay, the cell cycle was analyzed by flow cytometry, and protein expression and phosphorylation was examined by Western blot analysis. RESULTS: LGH00031 inhibited CDC25B irreversibly in vitro in a dose-dependent manner, and impaired the proliferation of tumor cell lines. In synchronized HeLa cells, LGH00031 delayed the cell cycle progression at the G(2)/M phase. LGH00031 increased cyclin-dependent kinase 1 (CDK1) tyrosine 15 phosphorylation and cyclin B1 protein level. The activity of LGH00031 against CDC25B in vitro relied on the existence of 1,4-dithiothreitol (DTT) or dihydrolipoic acid and oxygen. The oxygen free radical scavenger catalase and superoxide dismutase reduced the inactivation of CDC25 by LGH00031, confirming that reactive oxygen species (ROS) mediate the inactivation process in vitro. LGH00031 accelerated cellular ROS production in a dose-dependent manner, and N-acetyl cysteine (NAC) markedly decreased the ROS production induced by LGH00031. Correspondingly, the LGH00031-induced decrease in cell viability and cell cycle arrest, cyclin B1 protein level, and phosphorylation of CDK1 tyrosine 15 were also rescued by NAC that decreased ROS production. CONCLUSION: The activity of LGH00031 at the molecular and cellular level is mediated by ROS.

J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Aug 21; Zhan Y, Chen X, Zhao X, Zhong DLeuprolide is a synthetic nonapeptide that has two basic amino acids, arginine and histidine, in its structure. By selection of an appropriate analytical column and optimizing the mobile phase composition, an improved analytical method has been developed and validated to determine leuprolide concentrations in human serum. After methanol-induced protein precipitation of serum samples and Oasis((R)) HLB cartridge solid-phase extraction, leuprolide and an internal standard (alarelin) were analyzed on a C(18) column interfaced with a triple quadrupole tandem mass spectrometer with positive electrospray ionization. The mobile phase consisted of acetonitrile-water-propionic acid (20:80:0.05). The analyte and internal standard were both detected in the selective reaction monitoring mode. The method exhibited a linear range of 0.018-45.2ng/mL for leuprolide. The intra- and inter-assay precisions were 11.5% or less relative standard deviation (R.S.D.), and accuracy was within +/-2.8% relative error (RE). The lower limit of quantification (LLOQ) was identifiable and reproducible at 0.018ng/mL, with acceptable precision and accuracy. The validated LC-MS/MS method was tested to a clinical pharmacokinetic study of leuprolide after a single subcutaneous injection of 1mg leuprolide acetate in healthy male Chinese volunteers.

J Phys Chem A. 2009 Aug 27; Wang J, Gu J, Leszczynski JConjugated polymers (CPs) contain one pi-conjugated backbone and functional groups that could be ionized in high dielectric media. These materials combine the semiconducting and photon harvesting properties of electronically delocalized polymers with the charge-mediated behavior of polyelectrolytes. CPs can be used as highly responsive optical sensors for chemical and biological targets. The density functional theory (DFT) and the time-dependent density functional theory (TDDFT) approach were employed to simulate the absorption and emission spectra of poly[9,9'-bis(6''-N,N,N-trimethylammonium)hexyl]fluorene-co-alt-4,7-(2,1,3-benzothiadiazole) dibromide] (PFBT) in the present study. The influences on the spectra of the monomer unit F(BT)F due to stacking with the fluorene (F) and 2,1,3-benzothiadiazole (BT) units have been explored. The results suggest that stacking lowers the excitation and emission energy, facilitating detections of the polymers.

Org Lett. 2009 Aug 24; Chen HD, He XF, Ai J, Geng MY, Yue JMTrigochilides A (1) and B (2), two highly modified daphnane-type diterpenoids with 12-carbon-containing polyketide appendages at C-16 forming a macro-lactone with C-3, were isolated from the twigs and leaves of Trigonostemon chinensis. Their structures were elucidated by spectroscopic analysis. Trigochilides A (1) showed modest cytotoxicity against two tumor cell lines.