[Synthesis and antitumor activity of novel tetrahydro-beta-carboline derivatives as KSP inhibitors].

Inhibitors of kinesin spindle protein (KSP) are a promising class of anticancer agents that cause mitotic arrest and induce apoptosis of tumor cells. A series of novel tetrahydro-beta-carboline derivatives were synthesized as kinesin spindle protein inhibitor and evaluated as potential antitumor agents. All compounds showed promising KSP inhibitiory activity.

CPUYJ039, a newly synthesized benzimidazole-based compound, is proved to be a novel inducer of apoptosis in HCT116 cells with potent KSP inhibitory activity.

Objectives: This study investigated the antiproliferative and apoptotic activities of CPUYJ039, a newly synthesized benzimidazole-based kinesin spindle protein (KSP) inhibitor, on HCT116 cell lines.

Methods: KSP-inhibitory activity was tested using the malachite-green method. The in-vitro cell proliferation inhibitory activity of the sample was measured using WST reagent.

De novo design, synthesis and biological evaluation of 1,4-dihydroquinolin-4-ones and 1,2,3,4-tetrahydroquinazolin-4-ones as potent kinesin spindle protein (KSP) inhibitors.

Kinesin spindle protein (KSP) inhibitors are a promising class of anticancer agents that cause mitotic arrest in cells from a failure to form functional bipolar mitotic spindles. Here, we report the design, synthesis and biological evaluation of a novel series of 1,4-dihydroquinolin-4-ones and 1,2,3,4-tetrahydroquinazolin-4-ones using de novo design method. The synthesized compound was evaluated and proved to have potent inhibitory activities in the KSP ATPase.

Design, synthesis and bioevaluation of dihydropyrazolo[3,4-b]pyridine and benzo[4,5]imidazo[1,2-a]pyrimidine compounds as dual KSP and Aurora-A kinase inhibitors for anti-cancer agents.

Four series of dihydropyrazolo[3,4-b]pyridines and benzo[4,5]imidazo[1,2-a]pyrimidines were designed and synthesized as dual KSP and Aurora-A kinase inhibitors for anti-cancer agents by introducing some fragments of Aurora-A kinase inhibitors into our KSP inhibitor CPUYL064. A total of 19 target compounds were evaluated by two related enzyme inhibition assays and a cytotoxicity assay in vitro. The results showed that some target compounds could inhibit both enzymes, and several of them showed significant inhibition activity against HCT116 cell line.

Discovery of tetrahydro-beta-carbolines as inhibitors of the mitotic kinesin KSP.

Inhibitors of kinesin spindle protein (KSP) are a promising class of anticancer agents that cause mitotic arrest in cells from a failure to form functional bipolar mitotic spindles. Here, we report the synthesis and biological evaluation of a novel series of tetrahydro-beta-carboline analogs based on the structure of the known KSP inhibitor HR22C16. Preferred compounds 11b, 12a and 19b were identified as potent inhibitors in a KSP ATPase assay with good anti-proliferative activity in A549 cells.

A novel anti-platelet aggregation tripeptide from Agkistrodon acutus venom: isolation and characterization.

AAP, a tripeptide that inhibited rabbit platelet aggregation, was isolated from Agkistrodon acutus venom by ion-exchange, gel filtration and reverse-phase chromatography. Amino acid sequences which determined mainly by amino acid analyses and NMR spectroscopy indicated it was a tripeptide including pyroglutamic acid, asparagine and tryptophane residues. The ESMS experiment assigned a molecular weight of 429 Da.

Intracellular GSH and ROS levels may be related to galactose-mediated human lens epithelial cell apoptosis: role of recombinant hirudin variant III.

Oxidative processes in the lenses are the most commonly found damaging factor for the development of cataracts. Hirudin, a most potent inhibitor of thrombin as an antithrombic drug, also have potential use in cataracts. In order to investigate the mechanisms of hirudin against galactose-induced cataract at the cellular level.

[Synthesis and biological evaluation of tetrahydro-beta-carline derivatives].

Kinesin spindle protein (KSP/Eg5) is essential for the formation and maintenance of bipolar spindles during mitosis. Inhibition of this protein leads to cell cycle arrest and apoptosis without interfering other microtubule-dependent processes. Therefore, it is a potential target in cancer therapy.

[Primary structure determination of hirudin and reteplase fusion protein by LC/ESI-MS/MS spectrometry].

The aim is to determine the primary structure of a new hirudin and reteplase fusion protein (HV12p-rPA) by LC-ESI-MS/MS spectrometry. The molecular weight of the hirudin and reteplase fusion protein (HV12p-rPA) was measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The HV12p-rPA was digested with trypsin and chymotrypsin separately and the peptides in the digest mixtures were identified by LC-ESI-MS/MS.

Cloning, enzyme characterization of recombinant human Eg5 and the development of a new inhibitor.

The microtubule-dependent motor protein Eg5 is essential for the development and function of the mitotic spindle. Now it has become an anti-mitotic drug target in high throughput screening for anticancer dugs in vitro. Here is a protocol for cloning, expression and purification of a human Eg5 that codes for motor and linker domain in Escherichia coli BL21 (DE3) cells.

Enhanced anti-tumor effects achieved in a murine tumor model using combination therapy of recombinant human manganese superoxide dismutase and adriamycin.

Manganese superoxide dismutase (MnSOD) is the only primary antioxidant enzyme in mitochondria that scavenges superoxide radicals. Overexpressing MnSOD in cancer cells by cDNA transfection suppresses tumor formation and reverses malignant growth. In this study, we examined the effect of recombinant human manganese superoxide dismutase (rhMnSOD) alone and in combination with adriamycin (ADR) against solid tumors of sarcoma 180 in Institute of Cancer Research (ICR) mice.

Potential use of hirudin in diabetic cataract: a study of galactose mediated human lens epithelial cells injury.

Osmotic stress, together with weakened antioxidant defense mechanisms, is attributed to the changes observed in human diabetic cataract. The use of hirudin, an antithrombic agent, in the pathogenesis of human cataracts has not been studied so far. Since the epithelium is the metabolic unit of the lens, the effect of recombinant hirudin variant III (rHV3) on galactose-induced morphological changes and antioxidant status of human lens epithelial line SRA01/04 in culture was evaluated in this study.

[Application of HPLC-ESI-ITMS in the quality control of carboxyterminal sequence confirmation for insulin and insulin chain B].

Application of HPLC-ESI-ITMS in the quality control of carboxyterminal sequence confirmation for insulin and insulin chain B was studied. The solution of intact insulin or insulin chain B was added to the solution of carboxypeptidase P (CPP) and carboxypeptidase Y (CPY). Fractions of appropriate volume were removed at some appointed time points, acidified with the same amount of 1% formic acid to stop the digestion, and then briefly vortexed for HPLC-ESI-ITMS analysis.

Study on hepatoprotective effect of peptide S-8300 from shark liver.

Aim: To explore the effects of peptide S-8300 from shark liver (S-8300) on liver function as well as in regulating immune functions in experimental injury models.

Methods: Mice were administered with different doses of S-8300 for four consecutive days, followed by mice injected with tetrachloromethane (CCl(4)) on d 3. The activity of ALT, AST, LDH, SOD and contents of MDA and GSH in the mice liver were tested.

[Preliminary studies on in vitro and in vivo thrombolytic activities of thrombolytic enzyme from an induced Bacillus subtilis strain].

Objective: To separate and purify a novel thrombolytic enzyme (FSC2-13) from culture media of an induced Bacillus subtilis strain and to study its in vitro and in vivo thrombolytic activities.

Methods: Employed fibrin plate method, pyrogenation (heating up) fibrin plate method and SDS-PAGE were used respectively to study FSC2-13 hydrolyzing fibrin and fibrinogen in vitro. Investigations were made on its in vivo pharmacodynamics using rat thrombogenesis inhibition model after it was administrated by intestinal route.

[Protective effects of shark hepatic stimulator substance against acute hepatic injury induced by acetaminophen in mice].

Aim: To investigate the protective effects of shark hepatic stimulator substance (sHSS) against acute hepatic injury induced by acetaminophen (AAP) in mice.

Methods: Acute hepatic injury model of Balb/c mice was induced by a single intraperitoneal injection of AAP (200 mg.kg-1, i.