Search results for "indoles"
showing 10 items of 251 documents
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…
3-(6-Phenylimidazo [2,1-
2019
A new series of imidazo[2,1-b][1,3,4]thiadiazole derivatives was efficiently synthesized and screened for their in vitro antiproliferative activity on a panel of pancreatic ductal adenocarcinoma (PDAC) cells, including SUIT-2, Capan-1 and Panc-1. Compounds 9c and 9l, showed relevant in vitro antiproliferative activity on all three pre-clinical models with half maximal inhibitory concentration (IC50) ranging from 5.11 to 10.8 µM, while the compounds 9e and 9n were active in at least one cell line. In addition, compound 9c significantly inhibited the migration rate of SUIT-2 and Capan-1 cells in the scratch wound-healing assay. In conclusion, our results will support further studies to increa…
Asymmetric Organocatalytic Wittig [2,3]-Rearrangement of Oxindoles
2016
A highly enantioselective organocatalytic [2,3]-rearrangement of oxindole derivatives is presented. The reaction was catalyzed by squaramide, and this provides access to 3-hydroxy 3-substituted oxindoles in high enantiomeric purities.
Exploiting the Chiral Ligands of Bis(imidazolinyl)- and Bis(oxazolinyl)thiophenes : Synthesis and Application in Cu-Catalyzed Friedel–Crafts Asymmetr…
2021
Five new C2-symmetric chiral ligands of 2,5-bis(imidazolinyl)thiophene (L1–L3) and 2,5-bis(oxazolinyl)thiophene (L4 and L5) were synthesized from thiophene-2,5-dicarboxylic acid (1) with enantiopure amino alcohols (4a–c) in excellent optical purity and chemical yield. The utility of these new chiral ligands for Friedel–Crafts asymmetric alkylation was explored. Subsequently, the optimized tridentate ligand L5 and Cu(OTf)2 catalyst (15 mol%) in toluene for 48 h promoted Friedel–Crafts asymmetric alkylation in moderate to good yields (up to 76%) and with good enantioselectivity (up to 81% ee). The bis(oxazolinyl)thiophene ligands were more potent than bis(imidazolinyl)thiophene analogues for …
Palladium-catalyzed heteroaryl thioethers synthesis overcoming palladium dithiolate resting states inertness: Practical road to sulfones and NH-sulfo…
2018
International audience; We provide efficient synthetic access to heteroaryl sulfones in two-steps using a simple palladium-1,1'-bis [(diphenyl)phosphanyl]ferrocene catalyst to form in high yields variously functionalized heteroaromatic thioethers. Pyridinyl-containing substrates can be subsequently selectively oxidized into sulfones and NH-sulfoximines by using very mild oxidation conditions with a high functional group tolerance. In the palladium catalyzed C-S coupling of heteroaromatic thiols, reactivity limitation is attached with electron-deficient thiols. We show that this limitation can be resolved by the successful use of 2-bromoheteroarenes in the C-S coupling. We established herein…
Micellar liquid chromatographic separation of amino acids using pre- and post-column o -phthalaldehyde/ N -acetylcysteine derivatization
2000
Abstract The isocratic analysis of primary proteic amino acids using a C18 column, micellar mobile phases of sodium dodecyl sulphate (SDS) and 1-propanol at varying pH, and pre- and post-column formation of the o-phthalaldehyde (OPA)/N-acetyl- l -cysteine (NAC) isoindoles, is examined. An interpretive optimization strategy was applied to find the best separation conditions. For this purpose, empirical polynomial models were used to describe the elution behavior of the isoindoles and free amino acids, using as separation factors the concentrations of surfactant and modifier (two-factor problem), or these two factors and the pH of the mobile phase (three-factor problem). The separation of the…
Analysis of amino acids using serially coupled columns.
2017
Single conventional columns in reversed-phase LC are insufficient for analysing the isoindoles of primary amino acids, due to their limited functionality. An interesting possibility for increasing the separation power is the combination of several columns of different nature, where the length is modified by coupling small segments. This approach may require a considerable investment to have multiple lengths for each stationary phase. However, the combination of only two columns of fixed length can be enough to resolve satisfactorily relatively complex mixtures, provided that an optimised gradient program is applied. In this work, a mixture of 19 primary amino acid isoindoles found in protei…
Determination of the protein and free amino acid content in a sample using o-phthalaldehyde and N-acetyl-L-cysteine
1990
A spectrophotometric method is proposed for determining the protein content in a sample after total acid hydrolysis. In the procedure, free amino acids are caused to react with o-phthalaldehyde and N-acetyl-L-cysteine at pH 9.5, using isoleucine as the reference compound. Correction factors are used to take into account the differences between the molar absorptivities of the amino acid isoindoles and the recoveries of the amino acids after the hydrolysis treatment. The limit of detection was in the range 40-50 micrograms of protein, and the recoveries were usually 101 +/- 3% with a coefficient of variation lower than 4%. The free amino acid content in a partially hydrolysed protein was also…
Spectrophotometric determination of cystine by formation of an o-phthalaldehyde/N-acetyl-l-cysteine derivative
1989
Abstract Cystine reacts with o -phthalaldehyde (OPA) in the absence and presence of a thiol compound to yield different compounds. The use of N -acetyl- l -cysteine as thiol leads to the formation of two derivatives, likely simple and double isoindoles, where the disulfide bond remains unbroken. In contrast, mercaptoethanol gives rise to the reduction of the amino acid to form a cysteine derivative. Obtaining cystine isoindoles makes it possible to spectrophotometrically determine the amino acid after Chromatographic separation and is further evidence of the large stabilization effect produced by N -acetyl- l -cysteine in the formation of OPA-thiol derivatives.
Nucleophilic substitutions in the isoindole series as a valuable tool to synthesize derivatives with antitumor activity
2011
Abstract A novel synthetic approach to the synthesis of 3-substituted isoindoles through nucleophilic substitution of 3-halo derivatives by charged carbon, and neutral nitrogen, oxygen, and sulfur nucleophiles, assisted by a 1-acyl group, is reported. Aryl-thio-isoindoles, obtained through a direct nucleophilic substitution with sulfur nucleophiles, showed cytotoxic activity, with GI50 values from micromolar to sub-micromolar concentrations, against the total number of cell lines investigated.