Triazolopyridinyl-acrylonitrile derivatives as antimicrotubule agents: Synthesis, in vitro and in silico characterization of antiproliferative activity, inhibition of tubulin polymerization and binding thermodynamics.

In this paper we report the synthesis, in vitro anticancer activity, and the experimental/computational characterization of mechanism of action of a new series of E isomers of triazolo[4,5-b/c]pyridin-acrylonitrile derivatives (6c-g, 7d-e, 8d-e, 9c-f, 10d-e, 11d-e). All new compounds are endowed with moderate to interesting antiproliferative activity against 9 different cancer cell lines derived from solid and hematological human tumors. Fluorescence-based assays prove that these molecules interfere with tubulin polymerization.

Identification and quantitation of 4-bromo-2,5-dimethoxyamphetamine in seized blotters.

Blotters are usually impregnated with hallucinogens such as lysergic acid diethylamide (LSD); only rarely other psychoactive substances are detected. In this work we identified 4-bromo-2,5-dimethoxyamphetamine (DOB) and 2,5-dimethoxyamphetamine (DMA) in illicit blotters seized in Italy. This report describes a rapid method for the simultaneous identification and quantitation of DOB and its precursor (DMA) by liquid chromatography tandem mass spectrometry (LC-MS-MS), using 2,3-dimethoxyphenethylamine-d3 as internal standard.

Enantiomeric separation of 13 new amphetamine-like designer drugs by capillary electrophoresis, using modified-B-cyclodextrins.

An easy-to-prepare chiral CE method for the enantiomeric separation of 13 new amphetamine-like designer drugs, using CDs as chiral selectors, was developed. Sulfated-β-CD was found to be the best chiral selector among the three used (sulfated-β-CD, caroboxymethyl-β-CD, dimethyl-β-CD). The separation of the analytes was achieved in a fused-silica gel capillary at 20 °C using an applied voltage of +25 kV.

Determination of four thiophenethylamine designer drugs (2C-T-4, 2C-T-8, 2C-T-13, 2C-T-17) in human urine by capillary electrophoresis/mass spectrometry.

An analytical procedure for the simultaneous determination in human urine of four thiophenethylamine designer drugs (2C-T series) is reported. The quantitative analysis was performed by capillary electrophoresis with mass spectrometric detection (CE/MS), using 2,5-dimethoxy-4-methylthiophenethylamine-D(4) (2C-T-D(4)) as internal standard. In order to minimize interferences with matrix components and to preconcentrate target analytes, solid-phase extraction (SPE) was introduced in the method as a clean-up step.

Multi-residue analysis of eight thioamphetamine designer drugs in human urine by liquid chromatography/tandem mass spectrometry.

An analytical procedure for the simultaneous determination in human urine of several thioamphetamine designer drugs (2C-T and ALEPH series) is reported. The quantitative analysis was performed by liquid chromatography/tandem mass spectrometry and has been fully validated. The mass spectrometer was operated in positive-ion, selected reaction monitoring (SRM) mode.

LC-MS analysis of trimethoxyamphetamine designer drugs (TMA series) from urine samples.

A sensitive liquid chromatography-mass spectrometric (LC-MS) method for quantification of an active psychedelic hallucinogenic drugs (trimethoxyamphetamines) in human urine after solid-phase extraction (SPE) with C(18) cartridge was developed and validated. Chromatographic separation was achieved on reversed-phase Phenomenex 3.0 microm Polar Plus column (150 mm x 2.

Simultaneous determination of new thioamphetamine designer drugs in plasma by capillary electrophoresis coupled with mass spectrometry.

A simple method for the simultaneous identification and quantification of four 2,5-methylenedioxy derivatives of 4-thioamphetamine (ALEPH series) in plasma samples was developed. The method consists of solid-phase extraction (SPE) using a Bond Elut C(18) cartridge and capillary electrophoresis coupled with electrospray ionisation mass spectrometry (CE/ESI-MS). The SPE method used required only simple steps and provided a clean extract from which identification of each drug was feasible, even at low concentrations.

Chromophore-modified bis-benzo[g]indole carboxamides: synthesis and antiproliferative activity of bis-benzo[g]indazole-3-carboxamides and related dimers.

Tricyclic pyrazole dimers that comprise two kinds of CONH-(CH(2))(n)-N(CH(3))-(CH(2))(n)-NHCO bridges to which are linked potential DNA-intercalating groups such as 1H-benzo[g]indazole, 2H-benzo[g]indazole and 1,4-dihydroindeno[1,2-c]pyrazole were designed, synthesized and some of them evaluated in vitro by NCI (Bethesda, USA) against nine types of cancer cells. Compounds 2a, 2f-i and 2o-r demonstrated significant antiproliferative activity, all with GI(50) values in the low micromolar range. Preliminary analysis of the structure-activity relationship for dimers 2 indicated that: (i) in the ground terms (2a and 2k) antitumor activities were strongly related to the type of chromophore, (ii) in contrast, either 1H-benzo[g]indazole- or 1,4-dihydroindeno[1,2-c]pyrazole-dimers when bore a N(1)-aryl group (2g, 2h, 2i, 2o, 2p, 2q and 2r) generally showed a good level of antitumor potency and (iii) for the most representative compounds (pairs of compounds: 2g,2h; 2o,2p and 2q,2r) the length of the bridges did not significantly contribute to the variations in cytotoxicity.

Synthesis and D(2)-like binding affinity of new derivatives of N-(1-ethyl-2-pyrrolidinylmethyl)-4,5-dihydro-1H-benzo[g]indole-3-carboxamide and related 4H-[1]benzothiopyrano[4,3-b]pyrrole and 5,6-dihydro-4H-benzo[6,7]cyclohepta[b]pyrrole-3-carboxamide analogues.

Various new derivatives and structural analogues of N-(1-ethyl-2-pyrrolidinylmethyl)-4,5-dihydro-1H-benzo[g]indole-3-carboxamide (2a), a representative term of a series of 2-aminomethylpyrrolidinyl derived 4,5-dihydrobenzo[g]indolcarboxamides with good D(2)-like affinity, were synthesized and evaluated for their ability to bind to dopamine D(2)-like receptors in vitro. The structural contribution to D(2)-like receptor binding of the 4,5-dihydrobenzo[g]indole portion of the molecule was examined. From these studies, compound 2k, 2-chloro-N-(1-ethyl-2-pyrrolidinylmethyl)-5,6-dihydro-4H-benzo[6,7]cyclohepta[b]pyrrole-3-carboxamide, was found to possess a potent affinity for D(2)-like receptors.