Synthesis, Characterization, and Biological Evaluation of Benzimidazole Derivatives as Potential Anxiolytics

The synthesized benzimidazoles compounds were prepared from the condensation reaction between o-Phenylenediamine and various carbonyl compounds, in the presence of ammonium chloride as a catalyst. Ammonium chloride is a commercial and environmentally benign catalyst. The yield of all benzimidazole derivatives was found to be in the range of 75 – 94%. The purity of the compounds was ascertained by melting point and TLC. The synthesized compounds were characterized by using IR,1H NMR, and MASS spectral data together with elemental analysis. The synthesized benzimidazole compounds were screened for acute and chronic anti-anxiety activity in Wistar rats by using an elevated plus maze model with standard Diazepam. The synthesized compounds ZB, ZE, ZF, ZG, and ZH showed potent anti-anxiety activity when compared to the standard Diazepam. The compound ZH exhibited a higher anti-anxiety activity when compared to other prepared benzimidazoles. The results were subjected to statistical analysis by using one-way ANOVA followed by the Tukey-Kramer test, to calculate the significance

Targeting the PAI-1 Mechanism with a Small Peptide Increases the Efficacy of Alteplase in a Rabbit Model of Chronic Empyema

The incidence of empyema is increasing and associated with a mortality rate of 20% in patients older than 65 years. Since 30% of patients with advanced empyema have contraindications to surgical treatment, novel, low-dose, pharmacological treatments are needed. A Streptococcus pneumoniae-induced rabbit model of chronic empyema recapitulates the progression, loculation, fibrotic repair, and pleural thickening of human disease. Treatment with single chain (sc) urokinase (scuPA) or tissue type (sctPA) plasminogen activators in doses 1.0–4.0 mg/kg were only partially effective in this model. Docking Site Peptide (DSP; 8.0 mg/kg), which decreased the dose of sctPA for successful fibrinolytic therapy in acute empyema model did not improve efficacy in combination with 2.0 mg/kg scuPA or sctPA. However, a two-fold increase in either sctPA or DSP (4.0 and 8.0 mg/kg or 2.0 and 16.0 mg/kg sctPA and DSP, respectively) resulted in 100% effective outcome. Thus, DSP-based Plasminogen Activator Inhibitor 1-Targeted Fibrinolytic Therapy (PAI-1-TFT) of chronic infectious pleural injury in rabbits increases the efficacy of alteplase rendering ineffective doses of sctPA effective. PAI-1-TFT represents a novel, well-tolerated treatment of empyema that is amenable to clinical introduction. The chronic empyema model recapitulates increased resistance of advanced human empyema to fibrinolytic therapy, thus allowing for studies of muti-injection treatments

Curcumin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells: molecular mechanisms of apoptosis, migration and angiogenesis-7

<p><b>Copyright information:</b></p><p>Taken from "Curcumin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells: molecular mechanisms of apoptosis, migration and angiogenesis"</p><p>http://www.jmolecularsignaling.com/content/2/1/10</p><p>Journal of Molecular Signaling 2007;2():10-10.</p><p>Published online 4 Oct 2007</p><p>PMCID:PMC2082014.</p><p></p>h. Cell viability was measured at the end of 48 h by XTT assay. (B), LNCaP cells were treated with various concentrations of curcumin (0–30 μM) for 24 h, followed by treatment with TRAIL (50 nM) for another 24 h. Cell viability was measured at the end of 48 h by XTT assay. (C), PC-3 cells were seeded in soft agar and treated with curcumin (5–40 μM) in the presence or absence of TRAIL (25 nM). After three weeks, no of colonies were counted. Data represent mean ± SE. (D), LNCaP cells were seeded in soft agar and treated with curcumin (5–40 μM) in the presence or absence of TRAIL (50 nM). After three weeks, no of colonies were counted. Data represent mean ± SE. (E and F), Effects of dominant negative FADD on curcumin and/or TRAIL-induced apoptosis. PC-3 and LNCaP cells were transiently transfected with either control plasmid or plasmid expressing dominant negative FADD (DN-FADD) along with plasmid (pCMV-LacZ) encoding the β-galactosidase (β-Gal) enzyme. There was no difference in transfection efficiency among groups. Transfected cells were treated with curcumin (0, 10 or 20 μM) in the presence or absence of TRAIL (25 nM for PC-3 cells or 50 nM for LNCaP) for 48 h. Apoptosis was measured by DAPI staining. Data represent mean ± SE. * = significantly different from respective control; # and % = treatment groups were significantly different, P < 0.05

Curcumin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells: molecular mechanisms of apoptosis, migration and angiogenesis-6

<p><b>Copyright information:</b></p><p>Taken from "Curcumin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells: molecular mechanisms of apoptosis, migration and angiogenesis"</p><p>http://www.jmolecularsignaling.com/content/2/1/10</p><p>Journal of Molecular Signaling 2007;2():10-10.</p><p>Published online 4 Oct 2007</p><p>PMCID:PMC2082014.</p><p></p>unted under a microscope. Data represent mean ± SD. * = significantly different from control, P < 0.05. (B), HUVECs were seeded in 24-well plates containing matrigel. Cells were pretreated with ERK inhibitor (10 μM) for 3 h, followed by treatment with curcumin (40 μM) for 24 h. Capillary tubes were counted under a microscope. Data represent mean ± SD. * = significantly different from control, P < 0.05. (C), Picture of capillary tube formation. HUVECs were treated as described in B. Pictures of capillary tubes were taken by a microscope. (D), HUVECs were treated with various concentrations of curcumin (20, 40 and 60 μM) or DMSO (control). Migration of HUVEC cells through the membrane was determined after 24 h of incubation at 37°C using Transwell Boyden chamber. Cells that had migrated to the lower chamber were fixed with 90% ethanol, stained with hematoxylin and eosin, quantified by counting the number of cells under a microscope. Data represent mean ± SD. * = significantly different from control, P < 0.05. (E), HUVECs were pretreated with ERK inhibitor (10 μM) for 3 h, followed by treatment with curcumin (40 μM) or DMSO (control) for 24 h at 37°C. Cells migrated to the lower chamber were fixed, stained and quantified

Interactive effects of resveratrol and TRAIL on caspase activation and PARP cleavage

<p><b>Copyright information:</b></p><p>Taken from "Sensitization of TRAIL-resistant LNCaP cells by resveratrol (3, 4', 5 tri-hydroxystilbene): molecular mechanisms and therapeutic potential"</p><p>http://www.jmolecularsignaling.com/content/2/1/7</p><p>Journal of Molecular Signaling 2007;2():7-7.</p><p>Published online 24 Aug 2007</p><p>PMCID:PMC2018690.</p><p></p> (A), Effects of resveratrol and/or TRAIL on caspase-3 activity in LNCaP cells. Cells were treated with resveratrol (0–30 μM) in the presence or absence of TRAIL (50 nM) for 24 h. At the end of incubation period, caspase-3 activity was measured by flurometric assay. (B), Effects of resveratrol and/or TRAIL on caspase-8 activity. LNCaP cells were treated with resveratrol (0–30 μM) in the presence or absence of TRAIL (50 nM) for 24 h. At the end of incubation period, caspase-8 activity was measured by flurometric assay. (C), Effects of resveratrol and/or TRAIL on cleavage of pro-caspase-8, pro-caspase-3, pro-caspase-9 and PARP. LNCaP cells were pretreated with resveratrol (0, 10 or 20 μM) for 24 h followed by treatment with or without TRAIL (50 nM) for 24 h. At the end of incubation period, cells were harvested, and the Western blot analysis was performed to measure the expression of pro-caspase-8, cleaved-caspase-3, cleaved-caspase-9 and PARP. β-actin was used as a loading control

Curcumin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells: molecular mechanisms of apoptosis, migration and angiogenesis-2

<p><b>Copyright information:</b></p><p>Taken from "Curcumin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells: molecular mechanisms of apoptosis, migration and angiogenesis"</p><p>http://www.jmolecularsignaling.com/content/2/1/10</p><p>Journal of Molecular Signaling 2007;2():10-10.</p><p>Published online 4 Oct 2007</p><p>PMCID:PMC2082014.</p><p></p>alysis

Effects of resveratrol on the expressions of Bcl-2 family members and IAPs

<p><b>Copyright information:</b></p><p>Taken from "Sensitization of TRAIL-resistant LNCaP cells by resveratrol (3, 4', 5 tri-hydroxystilbene): molecular mechanisms and therapeutic potential"</p><p>http://www.jmolecularsignaling.com/content/2/1/7</p><p>Journal of Molecular Signaling 2007;2():7-7.</p><p>Published online 24 Aug 2007</p><p>PMCID:PMC2018690.</p><p></p> (A and B), Effects of resveratrol on protein expression of Bcl-2 family members. Cells were treated with resveratrol (0–20 μM) for 24 or 48 h. The expressions of Noxa, Bim, Bak, Bax, Bid, PUMA, Bcl-2, and Bcl-Xwere examined by Western blot analysis. Actin antibody was used as a loading control. Bim= Bim extra large, Bim= Bim large, Bim= Bim short. (C), Effects of resveratrol on the expressions of IAPs. Cells were treated with resveratrol (0–20 μM) for 24 or 48 h. Crude proteins were subjected to SDS-PAGE and immunoblotted with antibody specific for XIAP, survivin, cIAP1 or cIAP2. β-actin antibody was used as a loading control

Interactive effects of resveratrol and TRAIL on cell viability, colony formation and apoptosis in prostate cancer cells

<p><b>Copyright information:</b></p><p>Taken from "Sensitization of TRAIL-resistant LNCaP cells by resveratrol (3, 4', 5 tri-hydroxystilbene): molecular mechanisms and therapeutic potential"</p><p>http://www.jmolecularsignaling.com/content/2/1/7</p><p>Journal of Molecular Signaling 2007;2():7-7.</p><p>Published online 24 Aug 2007</p><p>PMCID:PMC2018690.</p><p></p> (A), Effects of resveratrol and/or TRAIL on cell viability in LNCaP cells. Cells were treated with various doses of resveratrol (0–30 μM) in the presence or absence of TRAIL (50 nM) for 48 h. Cell viability was measured by XTT assay as described in materials and methods. Data represent mean ± SD. * = Significantly different from respective control, P < 0.05. (B), Effects of resveratrol and/or TRAIL on apoptosis in human normal prostate epithelial cells (PrEC). PrEC were treated with resveratrol (20 μM) in the presence or absence of TRAIL (50 nM) for 48 h, and apoptosis was measured by TUNEL assay. (C), Effects of resveratrol and/or TRAIL on colony formation by LNCaP cells. Cells were treated with various doses of resveratrol (0–30 μM) in the presence or absence of TRAIL (50 nM). After three weeks, no of colonies were stained and counted. Data represent mean ± SD. * = Significantly different from respective control, P < 0.05. (D), Effects of different treatment combinations of resveratrol and TRAIL on apoptosis. LNCaP cells were treated with resveratrol (20 μM) in the presence or absence of TRAIL (50 nM). TRAIL was added simultaneously with resveratrol (cotreatment), before or after 24 h of resveratrol treatment. Apoptosis was measured by TUNEL assay. Data represent mean ± SD. * = Significantly different from respective control, P < 0.05