Novel benzimidazole-triazole hybrids as apoptosis inducing agents in lung cancer: Design, synthesis, F-radiolabeling & galectin-1 inhibition studies.

In this study, we have synthesized a new series of benzimidazole-triazole hybrids as galectin-1 (gal-1) mediated apoptosis-inducing agents, and evaluated for their potential anticancer activity against a panel of human cancer cell lines viz. breast cancer (MCF-7 and MDA-MB-231) lung cancer (A-549 and NCI-H460), and human keratinocyte cancer (HaCaT), using MTT assay. The target compound 7c exhibited an excellent growth inhibition against lung cancer (A-549 and NCI-H460) cells with an IC value of 0.

Involvement of Histamine 2 Receptor in Alpha 1 Adrenoceptor Mediated Cardiac Hypertrophy and Oxidative Stress in H9c2 Cardio Myoblasts.

Despite the involvement of ɑ1adrenergic (ɑ1AR) and Histamine 2 receptors (H2R) in cardiac hypertrophy (CH), their relationship is yet to be studied. Our study investigated interrelationship between them using in vitro CH model. H9c2 cardiomyoblasts were exposed to phenylephrine (ɑ1AR agonist-50 μM) in the presence, the absence of famotidine (H2R antagonist-10 μM) and BAY 11-7082 (NF-kB inhibitor-10 μM).

Synthesis, F-radiolabeling and apoptosis inducing studies of novel 4, 7-disubstituted coumarins.

In present study, a new series of 4, 7-disubstituted coumarin derivatives (7a-y) have been synthesized as galectin-1 targeting apoptosis inducing agents and evaluated for their in vitro cytotoxic potentials against a panel of selected human cancer cell lines namely, Brest (MCF7), Ovarian (SKOV3), Prostate (PC-3 & DU145) and normal embryonic kidney (HEK293T) cells, using MTT assay. Most of the compounds exhibited potent growth inhibitory action against the treated cancer cell lines with an IC range of 10-30 µM. Compound 7q exhibited a significant growth inhibition against prostate cancer (PC-3 & DU145) cell lines with an IC value of 7.

Synthesis of 1-benzyl-1H-benzimidazoles as galectin-1 mediated anticancer agents.

In our pursuit to develop novel non-carbohydrate small molecule Galectin-1 Inhibitors, we have designed a series of 1-benzyl-1H-benzimidazole derivatives and demonstrated their anticancer activity. The compound 6g, 4-(1-benzyl-5-chloro-1H-benzo[d]imidazol-2-yl)-N-(4-hydroxyphenyl) benzamide was found to be most potent with an IC of 7.01 ± 0.

Synthesis and biological evaluation of morpholines linked coumarin-triazole hybrids as anticancer agents.

A series of novel morpholines linked coumarin-triazole hybrids (6a-6v) has been synthesized and evaluated for their anti-proliferative potential on a panel of five human cancer cell lines, namely bone (MG-63), lung (A549), breast (MDA-MB-231), colon (HCT-15) and liver (HepG2), using MTT assay. Among all, the compound 6n {7-((1-(2,4-dichlorobenzyl)-1H-1,2,3-triazol-4-yl) methoxy)-4-((2,6-dimethylmorpholino) methyl)-2H-chromen-2-one} showed significant growth inhibition against MG-63 cells with an IC value of 0.80 ± 0.

Bioenhancing effects of naringin on atorvastatin.

Naringin (CAS no: 10236-47-2) is a flavonone glycoside obtained from Citrus paradisi (grapefruit), a natural bioenhancer and reported to enhance the bioavailability of drugs by inhibiting cytochrome P450 and P-glycoprotein (P-gp). The aim of the present study was to investigate the effect of naringin on antihyperlipidemic properties of atorvastatin (AST) in tyloxapol induced hyperlipidemic rats and the effects were supported with measurement of plasma concentrations of AST by HPLC method. Animals received AST along with naringin (15 and 30 mg/kg) shown higher percent reduction in both cholesterol and triglycerides levels, when compared to animals received AST alone at dose of 25 and 50 mg/kg and it was found that the higher percent reduction in cholesterol and triglycerides was proportional to increase in plasma concentration of AST.

Human Galectin-1 and Its Inhibitors: Privileged Target for Cancer and HIV.

Galectin 1(Gal-1), a β-galactoside binding mammalian lectin of 14KDa, is implicated in many signalling pathways, immune responses associated with cancer progression and immune disorders. Inhibition of human Gal-1 has been regarded as one of the potential therapeutic approaches for the treatment of cancer, as it plays a major role in tumour development and metastasis by modulating various biological functions viz. apoptosis, angiogenesis, migration, cell immune escape.

Formulation and Evaluation of Sintered Floating Tablets of Cefpodoxime Proxetil.

Objectives: To develop sintered floating tablets of CP using locust bean gum as a release-controlling material. CP is an orally- administered, extended-spectrum, semi-synthetic antibiotic of the cephalosporin class.

Materials And Methods: CP has a short elimination half-life, possesses high solubility, chemical, enzymatic stability and absorption profiles in acidic pH, which makes it a suitable candidate for formulation in a gastro-retentive dose form for improved bioavailability.

An efficient and facile green synthesis of bisindole methanes as potential Mtb FtsZ inhibitors.

The rising multidrug-resistant Mycobacterium tuberculosis (Mtb) strain made current anti-TB drug therapy ineffective and became a major health concern globally; hence it is crucial to develop new molecules against vital targets with a novel mechanism. Mtb Filamenting temperature sensitive protein Z (FtsZ), a tubulin homolog plays a major role in bacterial cell division, in the presence of GTP recruiting essential proteins for cell division and considered to be a potential target for drug discovery. Most of MtbFtsZ inhibitors known are of antibiotics from natural resources and suffer from cellular uptake, specificity.

Design, synthesis, in silico and antiproliferative evaluation of novel pyrazole derivatives as VEGFR-2 inhibitors.

As the blockade of the VEGFR-2 signaling pathway is a viable approach in cancer therapy, the present study focuses on a series of pyrazole based VEGFR-2 inhibitors that were designed on the basis of the hybridization approach, supported by docking and in silico computational studies. The designed compounds were synthesized through facile synthetic methods and the structures were confirmed by H NMR, C NMR, MS and elemental analysis. The compounds were screened for in vitro antiproliferative activity against the HT-29 (human colon cancer) and MCF-7 (human breast cancer) cell lines by MTT assay.

Design, synthesis, in silico toxicity prediction, molecular docking, and evaluation of novel pyrazole derivatives as potential antiproliferative agents.

A new series of pyrazole derivatives were designed by docking into vascular endothelial growth factor receptor-2 (VEGFR-2) kinase active site. The designed compounds were synthesized and evaluated for in vitro antiproliferative activity against HT-29 colon and PC-3 prostate cancer cell lines, and angioinhibitory activity in chorioallantoic membrane (CAM) model. Based on the obtained antiproliferative activity results of in vitro and CAM assay, compounds 4b, 4c, 4f, 5b, 5c and 5f were selected, and tested for anticancer activity using in vivo ehrlich ascites carcinoma (EAC) bearing mice.

Evaluation of glucose utilization capacity of bioactivity-guided fractions of Linn and (L.) Poit in isolated rat hemidiaphragm.

Introduction: Diabetes mellitus (DM) is a chronic disease characterized by high blood glucose levels due to absolute or relative circulating insulin levels. Plants represent a major potential source of drugs for treating diabetes. The study of plants having antidiabetic activity may give a new approach in the treatment of DM.

Ameliorating effect of piperine on behavioral abnormalities and oxidative markers in sodium valproate induced autism in BALB/C mice.

Post natal exposure to VPA (valproic acid) in mice induces behavioral deficits, abnormal sensitivity to sensory stimuli and self-injurious behavior, observed in autism. Piperine has been reported to have protective effect on brain. The present study aimed at evaluating effect of piperine on VPA induced neurobehavioral and biochemical alterations in BALB/c mice.

Evaluation of antinociceptive effects of Tragia plukenetii: A possible mechanism.

Tragia plukenetii R.Smith. (Euphorbiaceae) is an erect, prostate herb with sparsely hispid stinging hairs.

Statistically optimised ethosomes for transdermal delivery of tolterodine tartrate.

The aim of the current investigation is to optimize ethosomes statistically for enhancing transdermal potential of Tolterodine Tartrate (TT). Ethosomes bearing TT were prepared by cold method and characterized for various parameters like vesicle size, vesicle shape, surface morphology and % drug entrapment. Microscopic examinations suggest ethosomes as spherical unilamellar vesicles with a smooth surface.

Comparative evaluation of single and bilayered lamotrigine floating tablets.

Aim: The purpose of this study was to prepare lamotrigine (LM) bilayered and single layered floating tablets and to compare their release profiles.

Materials And Methods: LM floating tablets were prepared by direct compression method. Drug, hydroxy propyl methyl cellulose K4M, lactose monohydrate and polyvinylpyrrolidone K30 constitute controlled release layer components and floating layer components includes polymers and sodium bicarbonate.

Design of a novel bilayered gastric mucoadhesive system for localized and unidirectional release of lamotrigine.

Lamotrigine is a BCS class II drug with pH dependent solubility. The bilayered gastric mucoadhesive tablets of lamotrigine were designed such that the drug and controlled release polymers were incorporated in the upper layer and the lower layer had the mucoadhesive polymers. The major ingredients selected for the upper layer were the drug and control release polymer (either HPMC K15M or polyox) while the lower MA layer predominantly comprised of Carbopol 974P.

Protective effect of lawsone on L-Arginine induced acute pancreatitis in rats.

The efficacy of lawsone against L-arginine induced acute pancreatitis was determined at 24 h by determination of serum levels of amylase, lipase and proinflammatory cytokines [tumor necrosis factor (TNF)-alpha, C-reactive proteins and interleukin (IL)], pancreatic myeloperoxidase (MPO) activity, lipid peroxidation (thiobarbituric acid reactive substances (TBARS)], nitrate/nitrite levels, and the wet weight/body weight ratio. Lawsone and methylprednisolone treatments significantly attenuated the L-arginine- induced increases in pancreatic wet weight/body weight ratio, and decreased the serum levels of amylase and lipase, and TNF-alpha and IL-6 and significantly lowered pancreatic levels of MPO, TBARS, and nitrate/nitrite. The histoimmunological findings further proved the amelioration of pancreatic injury by lawsone and further proved anti-inflammatory and antioxidant agent property of lawsone.

Scientific evidence for traditional claim of anti-obesity activity of Tecomella undulata bark.

Ethnopharmacological Relevance: The bark of Tecomella undulata is traditionally claimed in the treatment of various disease ailments including obesity and cancer. Till now there are no studies about anti-obesity activity of Tecomella undulata bark.

Aim Of The Study: The present study was aimed to establish a scientific evidence for anti-obesity efficiency of ethyl acetate extract of Tecomella undulata bark (EATUB).

Synergistic effect of iontophoresis and chemical enhancers on transdermal permeation of tolterodine tartrate for the treatment of overactive bladder.

Purpose: The objective of the study was to evaluate the synergistic transdermal permeation effect of chemical enhancers and iontophoresis technique on tolterodine tartrate (TT) transdermal gel and to evaluate its pharmacokinetic properties.

Materials And Methods: Taguchi robust design was used for optimization of formulations. Skin permeation rates were evaluated using the Keshary-chein type diffusion cells in order to optimize the gel formulation.

Formulation and optimization of fenofibrate lipospheres using Taguchi's experimental design.

Fenofibrate lipospheres were prepared by the melt dispersion technique. Critical parameters influencing particle size and entrapment efficiency were optimized by applying the L9 Taguchi experimental design. Entrapment efficiency of up to 87 % was obtained for the optimized formulation on increasing olive oil up to 30 % in the lipid carrier.

Terpenes: Effect of lipophilicity in enhancing transdermal delivery of alfuzosin hydrochloride.

Transdermal drug delivery has attracted much attention as an alternative to intravenous and oral methods of delivery. But the main barrier is stratum corneum. Terpenes classes of chemical enhancers are used in transdermal formulations for facilitating penetration of drugs.

Effect of chemical enhancers in transdermal permeation of alfuzosin hydrochloride.

The objective of the present study is to explore the efficient chemical penetration enhancer among the various enhancers available in overcoming the stratum corneum barrier in transdermal delivery of Alfuzosin hydrochloride (AH). The different enhancers were incorporated in 2% Carbopol gel which was selected as a control and evaluated by in vitro diffusion studies through dialysis membrane and permeation through the rat abdominal skin using Keshary-Chien diffusion cells. All the enhancers increased the release rate through the dialysis membrane when compared with control except oleic acid which decreased the release rate but showed maximum solubility of the drug.