Search results for "Azoles"

The development of benzimidazoles as selective rho kinase inhibitors

2010

Rho Kinase (ROCK) is a serine/threonine kinase whose inhibition could prove beneficial in numerous therapeutic areas. We have developed a promising class of ATP-competitive inhibitors based upon a benzimidazole scaffold, which show excellent potency toward ROCK (IC(50)<10nM). This report details the optimization of selectivity for ROCK over other related kinases such as Protein kinase A (PKA).

Host-Nonspecific Iron Acquisition Systems and Virulence in the Zoonotic Serovar of Vibrio vulnificus

2014

ABSTRACT The zoonotic serovar of Vibrio vulnificus (known as biotype 2 serovar E) is the etiological agent of human and fish vibriosis. The aim of the present work was to discover the role of the vulnibactin- and hemin-dependent iron acquisition systems in the pathogenicity of this zoonotic serovar under the hypothesis that both are host-nonspecific virulence factors. To this end, we selected three genes for three outer membrane receptors ( vuuA , a receptor for ferric vulnibactin, and hupA and hutR , two hemin receptors), obtained single and multiple mutants as well as complemented strains, and tested them in a series of in vitro and in vivo assays, using eels and mice as animal models. Th…

Synthesis and chemical characterization of CuII, NiII and ZnII complexes of 3,5-bis(20-pyridyl)-1,2,4-oxadiazole and 3-(20-pyridyl)5-(phenyl)-1,2,4-o…

2011

The synthesis and structural characterization of NiII, CuII and ZnII complexes of two chelating 1,2, 4-oxadiazole ligands, namely 3,5-bis(20-pyridyl)-1,2,4-oxadiazole (bipyOXA) and 3-(20-pyridyl)5- (phenyl)-1,2,4-oxadiazole (pyOXA), is here reported. The formed hexacoordinated metal complexes are [M(bipyOXA)2(H2O)2](ClO4)2 and [M(pyOXA)2(ClO4)2], respectively (M = Ni, Cu, Zn). X-ray crystallography, 1H and 13C NMR spectroscopy and C, N, H elemental analysis data concord in attributing them an octahedral coordination geometry. The two coordinated pyOXA ligands assume a trans coplanar disposition, while the two bipyOXA ligands are not. The latter result is a possible consequence of the format…

Bioactive Azoles with Three Heteroatoms

2010

This issue is dedicated to scientists belonging to either or both the fields of heterocyclic and medicinal chemistry. Nowadays, pharmaceutical industries are more and more dedicating their research towards different use or applications of the same molecule rather than towards the development of new drugs. In the latter decades, in fact, the time which is necessary since a given molecule is synthesized to when it is approved as a drug has significantly increased. Therefore, the development of time-saving methodologies such as combinatorial chemistry and computationally driven drug design has attracted the interest of several organic and medicinal chemists. Many of the molecules tested in-vit…

Sintesi e valutazione biologica di 1,2,4-ossadiazoli analoghi del Linezolid

2011

Synthesis and biological evaluation of new 1,2,4-oxadiazole derivatives of Topsentin

New Frontiers in the Treatment of Homozygous Familial Hypercholesterolemia.

2021

: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder. The most common cause is a mutation in both alleles of the gene encoding for the low-density lipoprotein (LDL) receptor, although other causative mutations have been identified. Complications of atherosclerotic cardiovascular disease are common in these patients; therefore, reducing the elevated LDL-cholesterol burden is critical in their management. Conventionally, this is achieved by patients initiating lipid-lowering therapy, but this can present challenges in clinical practice. Fortunately, novel therapeutic strategies have enabled promising innovations in HoFH treatment. This review highlights recent and ongo…

High Fluorescence of Thioflavin T Confined in Mesoporous Silica Xerogels

2013

Trapping of organic molecules and dyes within nanoporous matrices is of great interest for the potential creation of new materials with tailored features and, thus, different possible applications ranging from nanomedicine to material science. The understanding of the physical basis of entrapment and the spectral properties of the guest molecules within the host matrix is an essential prerequisite for the design and control of the properties of these materials. In this work, we show that a mesoporous silica xerogel can efficiently trap the dye thioflavin T (ThT, a molecule used as a marker of amyloid fibrils and with potential drug benefits), sequestering it from an aqueous solution and pro…

Tuning size and thermal hysteresis in bistable spin crossover nanoparticles.

2010

Nanoparticles of iron(II) triazole salts have been prepared from water-organic microemulsions. The mean size of the nanoparticles can be tuned down to 6 nm in diameter, with a narrow size distribution. A sharp spin transition from the low spin (LS) to the high spin (HS) state is observed above room temperature, with a 30-40-K-wide thermal hysteresis. The same preparation can yield second generation nanoparticles containing molecular alloys by mixing triazole with triazole derivatives, or from metallic mixtures of iron(II) and zinc(II). In these nanoparticles of 10-15 nm, the spin transition "moves" towards lower temperatures, reaching a 316 K limit for the cooling down transition and mainta…

Identification and quantification of phosphatidylcholines containing very-long-chain polyunsaturated fatty acid in bovine and human retina using liqu…

2010

The retina is one of the vertebrate tissues with the highest content in polyunsaturated fatty acids (PUFA). A large proportion of retinal phospholipids, especially those found in photoreceptor membranes, are dipolyunsaturated molecular species. Among them, dipolyunsaturated phosphatidylcholine (PC) molecular species are known to contain very-long-chain polyunsaturated fatty acids (VLC-PUFA) from the n-3 and n-6 series having 24-36 carbon atoms (C24-C36) and four to six double bonds. Recent interest in the role played by VLC-PUFA arose from the findings that a protein called elongation of very-long-chain fatty acids 4 (ELOVL4) is involved in their biosynthesis and that mutations in the ELOVL…