Search results for "Azoles"

Synthesis and antiproliferative activity of the ring system [1,2]oxazolo[4,5-g]indole.

2012

Brand new ring: A series of 27 derivatives of the new ring system [1,2]oxazolo[4,5-g]indole were conveniently prepared and tested at the NCI for antiproliferative studies. Several of them showed good inhibitory activity toward all tested cell lines, reaching GI50 values generally at the micromolar and sub-micromolar levels and in some cases at nanomolar concentrations. The mean GI50 values, calculated on the full panel, were in the range 0.25-7.08 μM.

1-methil-3H-pyrazolo[1-2-a]benzo[1-2-3-4]tetrazin-3-ones, design synthesis and biological activity of new antitumoral agents

2005

1-Methylpyrazolo[1,2-a]benzo[1,2,3,4]tetrazin-3-ones 4, synthesized in good to excellent yields, were designed as novel alkylating agents because of their peculiar chemical behavior. All derivatives showed antiproliferative activity against more than 50 types of tumor cell lines with GI50 reaching sub-micromolar values. SAR studies revealed that the presence of a chlorine atom is well-tolerated in both positions 8 and 9, whereas in the case of the methyl group, switching from the 8 to the 9 position gives rise to the most active compound of the series, 4g, either for the number of cell lines inhibited and for selectivity against leukaemia and renal cancer subpanels. COMPARE and 3D-MIND comp…

Synthesis and Antitumor Activity of New Thiazole Nortopsentin Analogs

2016

New thiazole nortopsentin analogs in which one of the two indole units was replaced by a naphthyl and/or 7-azaindolyl portion, were conveniently synthesized. Among these, three derivatives showed good antiproliferative activity, in particular against MCF7 cell line, with GI50 values in the micromolar range. Their cytotoxic effect on MCF7 cells was further investigated in order to elucidate their mode of action. Results showed that the three compounds act as pro-apoptotic agents inducing a clear shift of viable cells towards early apoptosis, while not exerting necrotic effects. They also caused cell cycle perturbation with significant decrease in the percentage of cells in the G0/G1 and S ph…

Synthesis of tetrasubstituted-4,4'-biimidazoles with perspective heavy-metal sensing ability

2012

A frozen analogue approach to aminopyridinylimidazoles leading to novel and promising p38 MAP kinase inhibitors.

2012

In this study we report the design, synthesis, and biological evaluation of constrained aminopyridinylimidazoles as p38α MAP kinase inhibitors. The frozen analogue approach focused on the pyridinyl unit, using purine bioisosteres as constrained structure analogues. The identification of the most potent bioisostere was followed by a further derivatization to address hydrophobic region II. In combination with C-2 modifications of the imidazole core, we were able to design highly active inhibitors on the p38α MAP kinase. The inhibitor design presented herein represents a promising and highly efficient advancement of recent stages of development in this class of p38 MAP kinase inhibitors. In co…

Effect of buffer nature and concentration on the chromatographic performance of basic compounds in the absence and presence of 1-hexyl-3-methylimidaz…

2019

Abstract In reversed-phase liquid chromatography, the performance for basic compounds is affected by the interaction of the protonated (cationic) species with the anionic free silanols on the alkyl-bonded stationary phases. Using aqueous-organic mobile phases in the absence of additives, the retention may be too high, and the peaks be broad and asymmetric. The performance is improved by addition to the mobile phase of ionic liquids, from which 1-hexyl-3-methylimidazolium chloride ([C6MIm][Cl]) has especially good characteristics. A recent report has also revealed that the use of the phosphate system as buffer, at varying concentration and pH, may have a significant role in the chromatograph…

Design, Synthesis and Biological Evaluation of Novel Pyrazolo[1,2,4]triazolopyrimidine Derivatives as Potential Anticancer Agents

2021

Three novel pyrazolo-[4,3-e][1,2,4]triazolopyrimidine derivatives (1, 2, and 3) were designed, synthesized, and evaluated for their in vitro biological activity. All three compounds exhibited different levels of cytotoxicity against cervical and breast cancer cell lines. However, compound 1 showed the best antiproliferative activity against all tested tumor cell lines, including HCC1937 and HeLa cells, which express high levels of wild-type epidermal growth factor receptor (EGFR). Western blot analyses demonstrated that compound 1 inhibited the activation of EGFR, protein kinase B (Akt), and extracellular signal-regulated kinase (Erk)1/2 in breast and cervical cancer cells at concentrations…

Silanol suppressing potency of alkyl-imidazolium ionic liquids on C18 stationary phases

2011

Residual silanols on C18 columns yield undesirable slow-kinetics ion-exchange interactions with positively charged basic compounds that result in asymmetrical peaks, low efficiencies and long retention times. The purity of the silica employed as supporting material, and the technique used to form the bonded phase, which varies with the brand and manufacturer, give rise to different amounts of residual silanols in the packings, and consequently, different chromatographic performance. One of the most efficient and widespread strategies to reduce or even eliminate the different performance among columns is the addition of a reagent to the mobile phase to block the silanol sites. However, the i…

Base-catalyzed isomerization of 2-isoxazolines enables a two-step enantioselective synthesis of β-hydroxynitriles from enals.

2010

The asymmetric synthesis of β-hydroxynitriles remains a challenge in organic synthesis. Herein we report a convenient synthesis of β-hydroxynitriles from enantiomerically enriched 3-unsubstituted 2-isoxazolines via a base-catalyzed ring-opening reaction that takes place without loss of enantiopurity. In combination with organocatalytic enantioselective synthesis of 3-unsubstituted 2-isoxazolines, the ring-opening enables a short 2-step synthesis of β-hydroxynitriles from α,β-unsaturated aldehydes in high enantiomeric purity.

Supramolecular assemblies of phenyl-pyridyl-triazolopyridine and β-cyclodextrin as sensor of divalent cations in aqueous solution

2014

The chemosensor 3-phenyl-7-(pyrid-2-yl)-[1,2,3]triazolo[1,5-a]pyridine (PhPTP) used in combination with two different cyclodextrins, enable its solubilization and stabilization in aqueous solution. The behavior of the inclusion complex, and its binding ability in both cyclodextrins were investigated by means of absorption and fluorescence spectroscopy. The best results were obtained for PhPTP-DMβCD assembly, and its orientation in the DMβCD nano cavity was obtained by 2D-NMR. This inclusion geometry was confirmed by docking studies. The binary complex was proved as chemosensor upon the presence of different divalent cations in aqueous solutions. The PhPTP-DMβCD system, displays a high sensi…