Search results for "Azoles"
showing 10 items of 899 documents
Solution versus Fluorous versus Solid-Phase Synthesis of 2,5-Disubstituted 1,3-Azoles. Preliminary Antibacterial Activity Studies
2009
A small library of compounds with an oxa(thia)zole scaffold and structural diversity in both positions 2 and 5 has been synthesized. Double acylation of a protected glycine affords intermediate α-amido-β-ketoesters, which in turn can be dehydrated to afford 1,3-oxazoles or reacted with Lawesson’s reagent to furnish 1,3-thiazoles. This procedure was designed with its adaptation to fluorous techniques in mind. Thus, when a protected glycine with a fluorous tag in the ester moiety is used as a starting material, the synthesis can be easily completed without column chromatography purification of intermediate compounds with good to excellent yields, thus affording a suitable entry to the prepara…
Systematic review and mixed treatment comparison meta-analysis of randomized clinical trials of primary oral antifungal prophylaxis in allogeneic hem…
2014
Background Antifungal prophylaxis is a promising strategy for reducing invasive fungal infections (IFIs) in allogeneic hematopoietic cell transplant (alloHCT) recipients, but the optimum prophylactic agent is unknown. We used mixed treatment comparison (MTC) meta-analysis to compare clinical trials examining the use of oral antifungals for prophylaxis in alloHCT recipients, with the goal of informing medical decision-making. Methods Randomized controlled trials (RCTs) of fluconazole, itraconazole, posaconazole, and voriconazole for primary antifungal prophylaxis were identified through a systematic literature review. Outcomes of interest (incidence of IFI/invasive aspergillosis/invasive can…
Synthesis and in vitro antimicrobial activities of new (cyano-NNO-azoxy) pyrazole derivatives
2011
The antibacterial and antifungal activity of a series of products, in which the 1,5-dimethyl-4-(cyano- NNO-azoxy)pyrazol-3-yl and 1,3-dimethyl-4-(cyano-NNO-azoxy)pyrazol-5-yl moieties were linked to pyridine, pyrazole, isoxazole, thiophene and the furan ring, were examined. No molecule displayed activity against the Gram-negative bacteria tested. Conversely, some compounds displayed activity against two Staphylococcus aureus strains, including the methicillin resistant strain. All compounds displayed interesting antifungal activity, the most active compound of the series being the thiophene derivative 7a. This compound’s activity against Candida krusei and Candida glabrata (MIC = 0.25 and 0…
Translational readthrough of ciliopathy genes BBS2 and ALMS1 restores protein, ciliogenesis and function in patient fibroblasts
2021
Abstract Background Ciliary dysfunction underlies a range of genetic disorders collectively termed ciliopathies, for which there are no treatments available. Bardet-Biedl syndrome (BBS) is characterised by multisystemic involvement, including rod-cone dystrophy and renal abnormalities. Together with Alstrom syndrome (AS), they are known as the ‘obesity ciliopathies’ due to their common phenotype. Nonsense mutations are responsible for approximately 11% and 40% of BBS and AS cases, respectively. Translational readthrough inducing drugs (TRIDs) can restore full-length protein bypassing in-frame premature termination codons, and are a potential therapeutic approach for nonsense-mediated ciliop…
Non-Innocent Base Properties of 3- and 4-Pyridyl-dithia- and Diselenadiazolyl Radicals : The Effect of N-Methylation
2018
International audience; Condensation of persilylated nicotinimideamide and isonicotinimideamide with sulfur monochloride affords double salts of the 3-, 4-pyridyl-substituted 1,2,3,5-dithiadiazolylium DTDA cations of the general formula [3-, 4-pyDTDA][Cl][HCl] in which the pyridyl nitrogen serves as a noninnocent base. Reduction of these salts with triphenylantimony followed by deprotonation of the intermediate-protonated radical affords the free base radicals [3-, 4-pyDTDA], the crystal structures of which, along with those of their diselenadiazolyl analogues [3-, 4-pyDSDA], have been characterized by powder or single-crystal X-ray diffraction. The crystal structures consist of “pancake” π…
Influence of side chain characteristics on the aggregation-induced emission (AIE) properties of tetrasubstituted tetraphenylethylene (TPE)
2017
[EN] Five new tetraphenylethylene (TPE) derivatives were synthesised and their aggregation-induced emission (AIE) was evaluated in mixtures of THF/water and MeOH/water. The influence of regiochemistry and length of the chains in the substituents on emissive properties was studied.
Synthesis and characterisation of N-glycosyl amines from the reaction between 4,6-O-benzylidene-D-glucopyranose and substituted aromatic amines and a…
2001
Twelve N-glycosyl amines were synthesised using 4,6-O–benzylidene-D-glucopyranose and different substituted aromatic amines, including some diamines that resulted in bis-glycosyl amines. Another set of six N–glycosyl amines was synthesised using different hexoses and pentoses and 2–(o–aminophenyl)benzimidazole. All compounds were isolated as solid products and purified, their elemental compositions were established, and these were characterised by NMR (1H and 13C), UV–Vis, and FTIR spectroscopy, by FAB mass spectrometry (molecular-ion peaks gave molecular weights), and by their optical rotations. While the protected saccharide, 4,6-O-benzylidene-D-glucopyranose, exists as a mixture of β and…
Discovery of benzimidazole-based Leishmania mexicana cysteine protease CPB2.8ΔCTE inhibitors as potential therapeutics for leishmaniasis
2018
Abstract: Chemotherapy is currently the only effective approach to treat all forms of leishmaniasis. However, its effectiveness is severely limited due to high toxicity, long treatment length, drug resistance, or inadequate mode of administration. As a consequence, there is a need to identify new molecular scaffolds and targets as potential therapeutics for the treatment of this disease. We report a small series of 1,2‐substituted‐1H‐benzo[d]imidazole derivatives (9ad) showing affinity in the submicromolar range (Ki = 0.150.69 μM) toward Leishmania mexicanaCPB2.8ΔCTE, one of the more promising targets for antileishmanial drug design. The compounds confirmed activity in vitro against intrace…
Synthesis and Biological Properties of Benzothiazole, Benzoxazole, and Chromen-4-one Analogues of the Potent Antitumor Agent 2-(3,4-Dimethoxyphenyl)-…
2008
New fluorinated 2-aryl-benzothiazoles, -benzoxazoles, and -chromen-4-ones have been synthesized and their activity against MCF-7 and MDA 468 breast cancer cell lines compared with the potent antitumor benzothiazole 5. Analogues such as 9a, b and 12a, d yielded submicromolar GI50 values in both cell lines; however, none of the new compounds approached 5 in terms of antitumor potency. For 5, binding to the aryl hydrocarbon receptor appeared to be necessary but not sufficient for growth inhibition.
GSK-3? Can Regulate the Sensitivity of MIA-PaCa-2 Pancreatic and MCF-7 Breast Cancer Cells to Chemotherapeutic Drugs, Targeted Therapeutics and Nutra…
2021
Glycogen synthase kinase-3 (GSK-3) is a regulator of signaling pathways. KRas is frequently mutated in pancreatic cancers. The growth of certain pancreatic cancers is KRas-dependent and can be suppressed by GSK-3 inhibitors, documenting a link between KRas and GSK-3. To further elucidate the roles of GSK-3β in drug-resistance, we transfected KRas-dependent MIA-PaCa-2 pancreatic cells with wild-type (WT) and kinase-dead (KD) forms of GSK-3β. Transfection of MIA-PaCa-2 cells with WT-GSK-3β increased their resistance to various chemotherapeutic drugs and certain small molecule inhibitors. Transfection of cells with KD-GSK-3β often increased therapeutic sensitivity. An exception was observed wi…