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In pursuit of an anticancer lead, a library of 1,2,3-triazole derivatives (7a-x) was prepared, characterized and screened for in vitro cytotoxicity in different cell lines. Most of the compounds proved to be cytotoxic with IC 50 values in the low micromolar range. Further studies showed that the most active compound 7c induces caspase-dependent apoptosis in Jurkat cells by activating both the intrinsic and the extrinsic apoptotic pathways and perturbs cell-cycle progression. Moreover, 7c did not show any genotoxic activity. Molecular docking simulations were performed against epidermal growth factor receptor (EGFR). Docking experiments showed that, compounds 7c, 7o and 7 v bind within active sites of epidermal growth factor receptor EGFR (Pdb ID: 6P8Q) by strong hydrogen bonds with residue MET793, Pi-Sulfur with residue MET790 and Pi-Alkyl type interactions with residues LEU788, ALA743. The SwissADME webserver investigation suggested that most of the synthesized compounds follow the rules of drug-likeness., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Eight cyclic aliphatic amines, pyrrolidine (Py), piperidine (Pp), morpholine (M), piperazine (Pz), and the N-hydroxyethyl (HE) analogues, were employed to prepare a salt with acidic diclofenac (D). These salts were examined by thermal [differential scanning calorimetry (DSC), thermogravimetric analysis, and hot-stage microscopy (HSM)] and spectroscopic [Fourier transform infrared (FTIR), Raman, (1) H NMR, and ultraviolet] analysis. The results show the thermal instability of these salts: the thermal dissociation leaves the starting acidic D, evidenced by the FTIR and Raman spectra inside the molten mass of the salts with M and HEM. The nature of the salt with Pz (1:1 or 1:2) and HEPy (anhydrous or hydrate polymorph), but not for the salt with HEPz and Py, depends on the polarity of the solvent used for the preparation of the salt. Incomplete dehydration of the hydrate Py and Pz salts progressively modifies the thermogram profiles and originates false information. Melting of the salts with Pp, M, and HEM could be demonstrated by HSM, but not with DSC. The difficulty of providing a description of these salts in a simple way originates doubts on the utility of a wide application of aliphatic amines to prepare pharmaceutical salts with D, whose solubility in water does not significantly differ from that of the common sodium D., (Copyright © 2012 Wiley Periodicals, Inc.)

The use of 2,5-dimethyl-1H-pyrrole-3,4-dicarbaldehyde (DPD) as a pre-column derivatization reagent for HPLC (high performance liquid chromatography) analysis of octopamine (oct) and tyramine (tyr) is proposed. The compound reacts under mild conditions (2 min at ambient temperature) with primary amino groups. The derivatization conditions were optimized by considering different parameters (temperature, time and reagent concentration). The synthesized oct and tyr adducts were characterized by (1)H NMR (nuclear magnetic resonance), ESI-MS (electrospray ionization mass spectrometry), IR (infrared) and UV (ultraviolet). Derivative chromatographic separations were performed on a Sinergy Hydro-RP column (150 mm × 4.6 mm i.d.) using a mobile phase consisting of methanol and triethylammonium phosphate buffer (pH 3; 10mM) at varying composition gradient elution and at a flow rate of 0.8 mL/min. Detection was set at λ=320 nm. The obtained results were compared with those achieved by a validated direct HPLC method with detection at λ=275 nm using a Sinergy Polar-RP column (250 mm × 3 mm i.d.) by isocratic elution conditions with a mobile phase consisting of methanol/acetonitrile/sodium pentanesulphonate (SPS; pH 3; 10mM), 7.5:7.5:85 (v/v/v) at a flow rate of 0.3 mL/min. Derivatization method sensitivity proved to be ten times higher than direct method. Limit of detection of oct and tyr was 0.010 and 0.008 μg/mL, respectively. The reliability of the pre-column method was satisfactory also in terms of linearity (from 0.028 to 1.255 and 0.024 to 1.244 μg/mL for oct and tyr, respectively), precision (relative standard deviation ≤2, without significant differences between intra-day and inter-day data) and recovery (from 98.9 to 101.2%). The proposed method showed to be suitable for a reliable determination of oct and tyr traces in commercially available phytoproducts using the instrumentation usually present in any analytical laboratory., (Copyright © 2011 Elsevier B.V. All rights reserved.)