Search results for "imidazoles"
showing 10 items of 272 documents
Surface-Enhanced Raman Study of the Interactions between Tripodal Cationic Polyamines and Polynucleotides
2011
Raman and surface-enhanced Raman spectra of new DNA/RNA-binding compounds consisting of three imidazole (Im) and three pyridine (Py) rings connected by tripodal polyaminomethylene linkages were obtained by the near-infrared excitation at 1064 nm. Study of interactions of Im and Py polyamines with single-stranded RNA polynucleotides (poly A, poly G, poly C, poly U), double-stranded DNA polynucleotides (poly dAdT-poly dAdT, poly dGdC-poly dGdC) and calf thymus DNA (ct-DNA) by surface-enhanced Raman spectroscopy (SERS) reveals unambiguous enhancement of the Raman scattering from the small molecules as well as appearance of new bands in spectra associated mainly with nucleobases. The SERS exper…
Clostridium difficile toxin A induces expression of the stress-induced early gene product RhoB.
2004
Clostridium difficile toxin A monoglucosylates the Rho family GTPases Rho, Rac, and Cdc42. Glucosylation leads to the functional inactivation of Rho GTPases and causes disruption of the actin cytoskeleton. A cDNA microarray revealed the immediate early gene rhoB as the gene that was predominantly up-regulated in colonic CaCo-2 cells after treatment with toxin A. This toxin A effect was also detectable in epithelial cells such as HT29 and Madin-Darby canine kidney cells, as well as NIH 3T3 fibroblasts. The expression of RhoB was time-dependent and correlated with the morphological changes of cells. The up-regulation of RhoB was approximately 15-fold and was based on the de novo synthesis of …
Ambulatory Blood Pressure Values in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET)
2012
In the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial, telmisartan (T; 80 mg daily) and ramipril (R; 10 mg daily) caused similar clinic blood pressure (BP) reductions, with a similar incidence of cardiovascular and renal events. The R+T combination lowered clinic BP somewhat more with no further cardiovascular or renal protection. The aim of this substudy was to see whether these clinic BP changes reflected the changes of 24-hour BP, a BP with a better prognostic value. In 422 patients in whom 24-hour BP monitoring was performed either before or after 6 to 24 months of treatment, demographic and clinical characteristics were similar in the 3 treated groups.…
Prognostic value of blood pressure in patients with high vascular risk in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpo…
2009
Hypertension guidelines advise aggressive blood pressure (BP) lowering in patients with diabetes or high cardiovascular risk, but supporting evidence is limited. We analysed the impact of BP on cardiovascular events in well treated high-risk patients enrolled in a large clinical trial (Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial).Twenty-five thousand five hundred and eighty-eight patients with atherosclerotic disease or diabetes with organ damage, tolerant to angiotensin-converting enzyme inhibitors, were randomized to ramipril, telmisartan or both. We related the primary composite outcome and its components to: baseline SBP; SBP changes from baseline to…
Lack of antiandrogenic effects of topical bifonazole on sebaceous glands and hairs in the hamster flank organ.
1993
The activity of topically applied bifonazole was evaluated in vivo in the three androgen-dependent structures of the hamster flank organ, i.e. the pigmented spot, sebaceous glands and hairs. Topical bifonazole in our experience did not demonstrate any morphological effect on sebaceous gland and hair even when applied in the dosage of 3 mg/cm<sup>2</sup>/day. On the basis of our morphometric results we can conclude that topically applied bifonazole does not interfere with cutaneous androgen metabolic transformations in the pilosebaceous unit of the flank organ.
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).
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…
Synthesis and Characterization of New Bivalent Agents as Melatonin- and Histamine H3-Ligands
2014
Melatonin is an endogenous molecule involved in many pathophysiological processes. In addition to the control of circadian rhythms, its antioxidant and neuroprotective properties have been widely described. Thus far, different bivalent compounds composed by a melatonin molecule linked to another neuroprotective agent were synthesized and tested for their ability to block neurodegenerative processes in vitro and in vivo. To identify a novel class of potential neuroprotective compounds, we prepared a series of bivalent ligands, in which a prototypic melatonergic ligand is connected to an imidazole-based H3 receptor antagonist through a flexible linker. Four imidazolyl-alkyloxy-anilinoethylami…
Hypoxia-Selective Dissociation Mechanism of a Nitroimidazole Nucleoside in a DNA Environment
2019
Photodynamic therapy is a promising approach to treat a variety of superficial tumors and other diseases. One of its major limitations arises from its dependence on molecular oxygen, which decreases the efficiency of the therapy in hypoxia conditions commonly developed by solid tumors. The present contribution reveals the molecular mechanism of a modified thymine bearing a nitroimidazole substituent, a photosensitizer able to produce highly harmful interstrand cross-links in the DNA double strand after irradiation selectively in absence of oxygen. The mechanism is resolved at a fully atomistic and electronic level relying on quantum mechanics (CASPT2, coupled-cluster, DFT, and TD-DFT method…
Geminal Imidazolium Salts: A new Class of Gelators
2012
The gelling behavior of some geminal diimidazolium salts was investigated in solvents differing in polarity and hydrogen bond donor ability. The used salts, namely the 3,3'-di-n-decyl-1,1'(1,4-phenylenedimethylene)diimidazolium dibromide [p-Xyl-(decim)(2)][Br](2) (1), the 3,3'-di-n-dodecyl-1,1'(1,4-phenylenedimethylene)diimidazolium dibromide [p-Xyl-(dodecim)(2)][Br](2) (2), and the 3,3'-di-n-dodecyl-1,1'(1,4-phenylenedimethylene)diimidazolium ditetrafluoroborate [p-Xyl-(dodecim)(2)][BF(4)](2) (3), differ in the alkyl chain length and in the anion properties, such as size, shape, and coordination ability. In all cases in which gelation process was observed, the obtained gels were characteri…