Discovery of highly potent tubulin polymerization inhibitors: Design, synthesis, and structure-activity relationships of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidines.

By removing 5-methyl and 6-acetyl groups in our previously reported compound 3, we designed a series of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine derivatives as potential tubulin polymerization inhibitors. Among them, compound 5e displayed low nanomolar antiproliferative efficacy on HeLa cells which was 166-fold higher than the lead analogue 3. Interestingly, 5e displayed significant selectivity in inhibiting cancer cells over HEK-293 (normal human embryonic kidney cells).

Synthesis and biological evaluation of benzofuran-based 3,4,5-trimethoxybenzamide derivatives as novel tubulin polymerization inhibitors.

A new series of derivatives characterized by the presence of the 3,4,5-trimethoxylbenzamide substituted benzofurans were synthesized and evaluated for antiproliferative activity against four cancer cell lines and one normal human cell line. Among them, derivative 6g with greatest cytotoxicity significantly inhibited the growth of MDA-MB-231, HCT-116, HT-29 and HeLa cell lines with IC values of 3.01, 5.

Discovery and optimization of 3,4,5-trimethoxyphenyl substituted triazolylthioacetamides as potent tubulin polymerization inhibitors.

Based on our previous research, three series of new triazolylthioacetamides possessing 3,4,5-trimethoxyphenyl moiety were synthesized, and evaluated for antiproliferative activities and inhibition of tubulin polymerization. The most promising compounds 8b and 8j demonstrated more significant antiproliferative activities against MCF-7, HeLa, and HT-29 cell lines than our lead compound 6. Moreover, analogues 8f, 8j, and 8o manifested more potent antiproliferative activities against HeLa cell line with IC values of 0.

Protective role of 6-Hydroxy-1-H-Indazole in an MPTP-induced mouse model of Parkinson's disease.

This study aimed to explore the neuroprotective role of 6-hydroxy-1H-indazole on dopaminergic neurons in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). Forty 12-week-old C57BL/6 male mice were were randomized divided into 4 groups. Mice were treated with 2mg/kg and 4mg/kg 6-hydroxy-1H-indazole (i.

1,3,4-tri-O-galloyl-6-O-caffeoyl-β-D-glucopyranose, a new anti-proliferative ellagitannin, regulates the expression of microRNAs in HepG(2) cancer cells.

Objective: MicroRNAs (miRNAs) play important roles in cell proliferation, differentiation and apoptosis. 1, 3, 4-tri-O-galloyl-6-O-caffeoyl-β-D-glucopyranose (BJA32515) is a new natural ellagitannin compound extracted from Balanophora Japonica MAKINO. The effect of BJA32515 on the expression of miRNAs in cancer cells has not yet been explored.

Geniposide inhibits high glucose-induced cell adhesion through the NF-kappaB signaling pathway in human umbilical vein endothelial cells.

Aim: To investigate whether geniposide, an iridoid glucoside extracted from gardenia jasminoides ellis fruits, inhibits cell adhesion to human umbilical vein endothelial cells (HUVECs) induced by high glucose and its underlying mechanisms.

Methods: HUVECs were isolated from human umbilical cords and cultured. The adhesion of monocytes to HUVECs was determined using fluorescence-labeled monocytes.

[Bioequivalence evaluation of orally disintegrating tablet of pentoxyverine citrate].

Objective: To evaluate the bioequivalence of orally disintegrating tablets of pentoxyverine citrate (tested preparation) in healthy male volunteers.

Methods: A single oral dose of the tested and reference preparations at 25 mg were given to 20 healthy volunteers in a randomized two-period cross-over design. Plasma pentoxyverine citrate concentrations were determined by HPLC-MS/ESI+ method.

[Cough-relieving, analgesic and antibiotic effects of durian shell extracts: a study in mice].

Objective: To investigate the cough-relieving, analgesic and antibiotic effects of durian shell extract (DSE) in relieving cough and its analgesic and antibiotic effects.

Methods: The effect of DSE in relieving cough was assessed in mice challenged with ammonia and SO(2) to induce coughing. The analgesic and antibiotic effects of DSE in mice were evaluated by hot plate test and twisting reaction induced by acetic acid, and by minimal inhibitory concentration (MIC) and disc-agar diffusion tests, respectively.

[Naringin inhibits monocyte adhesion to high glucose-induced human umbilical vein endothelial cells].

Objective: To investigate the inhibitory effect of naringin on monocyte adhesion to high glucose-induced human umbilical vein endothelial cells (HUVECs).

Methods: Cultured HUVECs isolated from human umbilical cords were pretreated with or without naringin and induced with high glucose (33 mmol/L) for 48 h. Human monocyte THP-1 cells, after labeling with BCECF-AM, were co-cultured with the HUVECs for 30 min.

Effect of astragaloside IV on hepatic glucose-regulating enzymes in diabetic mice induced by a high-fat diet and streptozotocin.

Aim: Hepatic glycogen phosphorylase (GP) and glucose-6-phosphatase (G6Pase) are important in control of blood glucose homeostasis, and are considered to be potential targets for antidiabetic drugs. Astragaloside IV has been reported to have a hypoglycemic effect. However, the biochemical mechanisms by which astragaloside IV regulates hepatic glucose-metabolizing enzymes remain unknown.

Genipin inhibits endothelial exocytosis via nitric oxide in cultured human umbilical vein endothelial cells.

Aim: Exocytosis of endothelial Weibel-Palade bodies, which contain von Willebrand factor (VWF), P-selectin and other modulators, plays an important role in both inflammation and thrombosis. The present study investigates whether genipin, an aglycon of geniposide, inhibits endothelial exocytosis.

Methods: Human umbilical vein endothelial cells (HUVECs) were isolated from umbilical cords and cultured.

Effect of geniposide, a hypoglycemic glucoside, on hepatic regulating enzymes in diabetic mice induced by a high-fat diet and streptozotocin.

Aim: Hepatic glycogen phosphorylase (GP) and glucose-6-phosphatase (G6Pase) play an important role in the control of blood glucose homeostasis and are proposed to be potential targets for anti-diabetic drugs. Geniposide is an iridoid glucoside extracted from Gardenia jasminoides Ellis fruits and has been reported to have a hypoglycemic effect. However, little is known about the biochemical mechanisms by which geniposide regulates hepatic glucose-metabolizing enzymes.

[Isolation and characterization of the anti-HIV active component from Eucommia ulmoides].

Objective: To investigate the anti-HIV effects of Eucommia ulmoides Oliver, so as to provide experimental basis for searching a new efficacious drug for treatment of AIDS.

Methods: Using phytochemistry to isolate compounds from Eucommia ulmoides Oliver, the inhibitory activity of Samples on the HIV gp41 six-helix bundle formation was determined by a modified sandwich ELISA and PAGE.

Results: The Samples from Eucommia ulmoides Oliver had potent inhibitory activity on the HIV gp41 six-helix bundle formation.

[Hydrocamptothecin promotes the mRNA expression of Wnt signaling inhibitor DKK-1].

Objective: To investigate the effects of hydrocamptothecin on the expression of Wnt signaling pathway inhibitor DKK-1 in tumor cells.

Methods: Human HepG2, Hep3B, LoVo and U251 cells were treated with the antitumor drug Hydrocamptothecin. DKK-1 mRNA expression in the cells was detected with RT-PCR, and beta-catenin expression was measured by fluorescence-activated cell sorting (FACS).

[Inhibitory effect of polysaccharides on the six-alpha-helix bundle formation of HIV gp41 protein].

Objective: To compare the in vitro inhibitory effect of expolysaccharides from Streptomyces, polysaccharides of Ganoderma lucidum and rice bran on six-alpha-helix bundle formation of HIV gp41 protein.

Methods: The amount of six-alpha-helix bundle formed in the presence of N36 and C34 was tested by ELISA in response to treatments with different doses of polysaccharides.

Results: Expolysaccharides from Streptomyces potentially inhibited six-alpha-helix bundle formation with the effective concentration (IC(50)) of 145.

[Anti-oncogene p53-induced expression of secreted frizzled-related protein, a Wnt signaling inhibitor].

Objective: To investigate the effects of anti-oncogene p53 on the expression of secreted frizzled-related protein (sFRP), a Wnt pathway inhibitor.

Methods: Human hepatocarcinoma Hep3B cells were transfected with a replication-defective adenovirus encoding p53 (Adp53), and Adp53 transgene expression was measured by fluorescence-activated cell sorting (FACS) and sFRP mRNA expression detected by reverse transcriptional (RT)-PCR.

Results: sFRP mRNA expression in Hep3B cells was potentiated 20 h after the transfection with Adp53, reaching the peak level at 32 h.

Effect of E1B mutant adenovirus on p53-deficient leukemic cells.

OBJECTIVE: To study the effect of E1B mutant adenovirus (dl1520) on 3 p53-deficient leukemic cell lines K562, Jurkat and HL-60. METHODS: The replication efficiency of dl1520 in the 3 leukemic cell lines was assessed by plaque assay, and the number of cells killed by the adenovirus determined by using trypan-blue in a course of 10 d following the infection. RESULTS: The replication efficiency of dl1520 in the 3 leukemic cell lines was significantly lower than that in the positive control, and no significant cytocidal effect against the 3 cell lines was observed.