Search results for "Amides"
showing 10 items of 552 documents
5-Substituted-benzylsulfanyl-thiophene-2-sulfonamides with effective carbonic anhydrase inhibitory activity: Solution and crystallographic investigat…
2017
Abstract A series of 5-substituted-benzylsulfanyl-thiophene-2-sulfonamides was prepared by reacting 5-bromo-thiophene-2-sulfonamide with 5-substituted-benzyl mercaptans. The new compounds were investigated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The cytosolic human (h) isoforms hCA I was poorly inhibited by the new sulfonamides (KIs in the range of 683–4250 nM), whereas hCA II, and the transmembrane, tumor associated isoforms hCA IX and XII were effectively inhibited in the subnanomolar–nanomolar range. A high resolution X-ray crystal structure of the adduct of hCA II with one of the new sulfonamides allowed us to rationalize the excellent inhibitory activity of these heterocycli…
In silico identification and experimental validation of hits active against KPC-2 β-lactamase
2018
Bacterial resistance has become a worldwide concern, particularly after the emergence of resistant strains overproducing carbapenemases. Among these, the KPC-2 carbapenemase represents a significant clinical challenge, being characterized by a broad substrate spectrum that includes aminothiazoleoxime and cephalosporins such as cefotaxime. Moreover, strains harboring KPC-type β-lactamases are often reported as resistant to available β-lactamase inhibitors (clavulanic acid, tazobactam and sulbactam). Therefore, the identification of novel non β-lactam KPC-2 inhibitors is strongly necessary to maintain treatment options. This study explored novel, non-covalent inhibitors active against KPC-2, …
The longevity assurance homologue of yeast lag1 (Lass) gene family (Review)
2009
The Lass gene family contains a group of highly conserved genes that are found in eukaryotic species. The founding member, lag1, was discovered in a screen for yeast longevity genes. Subsequently, lag1 homologs were discovered in other organisms including six mammalian paralogs. All Lass genes encode a highly conserved Lag1 domain and many also have an additional Hox domain. Lass proteins are ceramide synthases and therefore are critical for ceramide biosynthesis. Ceramide synthase is also a critical enzyme in the sphingolipid biosynthetic pathway. As ceramide and sphingolipids are key intermediates in diverse cellular processes such as cell growth, apoptosis, and stress response and may al…
Combination of the novel farnesyltransferase inhibitor RPR130401 and the geranylgeranyltransferase-1 inhibitor GGTI-298 disrupts MAP kinase activatio…
1999
To test the Kirsten-Ras (Ki-Ras) alternative prenylation hypothesis in malignant transformation, we used a novel farnesyltransferase inhibitor competitive to farnesyl-pyrophosphate, RPR130401, and a CaaX peptidomimetic geranylgeranyltransferase-1 inhibitor GGTI-298. In Ki-Ras-overexpressing transformed adrenocortical cells, RPR130401 at 1-10 microM inhibited very efficiently the [(3)H]farnesyl but not [(3)H]geranylgeranyl transfer to Ras. However, proliferation of these cells was only slightly sensitive to RPR130401 (IC(50)=30 microM). GGTI-298 inhibited the growth of these cells with an IC(50) of 11 microM but cell lysis was observed at 15 microM. The combination of 10 microM RPR130401 and…
New biodegradable hydrogels based on a photocrosslinkable modified polyaspartamide: synthesis and characterization
1999
Abstract α,β-Poly( N -2-hydroxyethyl)- dl -aspartamide (PHEA), a synthetic water-soluble biocompatible polymer, was derivatized with glycidyl methacrylate (GMA), in order to introduce in its structure chemical residues having double bonds and ester groups. The obtained copolymer (PHG) contained 29 mol% of GMA residues. PHG aqueous solutions at various concentrations ranging from 30 to 70 mg/ml were exposed to a source of UV rays at λ 254 nm in the presence or in the absence of N , N ′-methylenebisacrylamide (BIS); the formation of compact gel phases was observed beginning from 50 mg/ml. The obtained networks were characterized by FT-IR spectrophotometry and swelling measurements which evide…
Highly sensitive monoclonal antibody-based immunoassays for the analysis of fluopyram in food samples
2019
Monoclonal antibody-based techniques have become a useful analytical technology in the agro-food sector. Nowadays, residues of the recently registered fungicide fluopyram are increasingly being found in quality control programs. In the present study, novel chemical derivatives of this pesticide were prepared and specific and high-affinity monoclonal antibodies to fluopyram were raised for the first time. Moreover, immunoassays to fluopyram were developed in two alternative enzyme-linked immunosorbent assay formats, using homologous and heterologous assay conjugates, with limits of detection below 0.05 µg L−1. The optimized immunoassays were applied to the analysis of fluopyram in fortified …
Microtubule distribution in gravitropic protonemata of the mossCeratodon
1990
Tip cells of dark-grown protonemata of the moss Ceratodon purpureus are negatively gravitropic (grow upward). They possess a unique longitudinal zonation: (1) a tip group of amylochloroplasts in the apical dome, (2) a plastid-free zone, (3) a zone of significant plastid sedimentation, and (4) a zone of mostly non-sedimenting plastids. Immunofluorescence of vertical cells showed microtubules distributed throughout the cytoplasm in a mostly axial orientation extending through all zones. Optical sectioning revealed a close spatial association between microtubules and plastids. A majority (two thirds) of protonemata gravistimulated for > 20 min had a higher density of microtubules near the lowe…
H89 enhances the sensitivity of cancer cells to glyceryl trinitrate through a purinergic receptor-dependent pathway
2014
// Marion Cortier 1, 2, 3 , Rahamata Boina-Ali 1, 2, 3 , Cindy Racoeur 1, 2, 3 , Catherine Paul 1, 2, 3 , Eric Solary 2, 4, 5 , Jean-Francois Jeannin 1, 2, 3 , Ali Bettaieb 1, 2, 3 1 EPHE, Tumor Immunology and Immunotherapy Laboratory, Dijon, F-21000, France 2 Inserm U866, Dijon, F-21000, France 3 EA7269, University of Burgundy, Dijon, F-21000, France 4 Inserm UMR1009, Gustave Roussy Institute, Villejuif F-94805, France 5 University Paris-Sud, Faculty of Medicine, Le Kremlin-Bicetre, F-94800, France Correspondence to: Ali Bettaieb, e-mail: ali.bettaieb@u-bourgogne.fr Keywords: H89, GTN, cancer, purinergic receptors, cGMP Received: October 08, 2014 Accepted: January 09, 2015 Publis…
Fluorine Scan of Inhibitors of the Cysteine Protease Human Cathepsin L: Dipolar and Quadrupolar Effects in the π-Stacking of Fluorinated Phenyl Rings…
2016
The π-stacking of fluorinated benzene rings on protein backbone amide groups was investigated, using a dual approach comprising enzyme-ligand binding studies complemented by high-level quantum chemical calculations. In the experimental study, the phenyl substituent of triazine nitrile inhibitors of human cathepsin L (hCatL), which stacks onto the peptide amide bond Gly67-Gly68 at the entrance of the S3 pocket, was systematically fluorinated, and differences in inhibitory potency were measured in a fluorimetric assay. Binding affinity is influenced by lipophilicity (clog P), the dipole and quadrupole moments of the fluorinated rings, but also by additional interactions of the introduced fluo…
In vitro mammalian metabolism of the mitosis inhibitor zoxamide and the relationship to its in vitro toxicity.
2009
The in vitro mammalian metabolism of the fungicide zoxamide is related to its in vitro mammalian toxicity. After incubation of zoxamide with rat liver microsomes leading to practically 100% metabolism (mostly hydroxylated zoxamide), the cytotoxicity (methyl thiazole tetrazolium (MTT) test) and the mitosis-inhibiting potential (shown by cell count and by cell cycle analysis) for V79 were not distinguishable from those of zoxamide, demonstrating that the hydroxylation of zoxamide did not change the cytotoxicity or mitosis-inhibiting potential as determined by these assays. After incubation of zoxamide with rat liver S9 predominantly leading to conjugation with glutathione, and after incubatio…