1,2,3-Triazolo[4,5-b]aminoquinolines: Design, synthesis, structure, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, and molecular docking of novel modified tacrines.

An efficient [4 + 2] cyclization protocol to synthesize a series of twelve examples of 1,2,3-triazolo[4,5-b]aminoquinolines (5) as novel structurally modified tacrines was obtained by reacting readily accessible precursors (i.e., 3-alky(aryl)-5-amino-1,2,3-triazole-4-carbonitriles (3)) and selected cycloalkanones (4) of five-, six-, and seven-membered rings. We evaluated the AChE and BChE inhibitory activity of the novel modified tacrines 5, and the compound derivatives from cyclohexanone (4b) showed the best AChE and BChE inhibitory activities. Specifically, 1,2,3-triazolo[4,5-b]aminoquinolines 5bb obtained from 3-methyl-carbonitrile (3b) showed the highest AChE (IC50 = 12.01 µM), while 5ib from 3-sulfonamido-carbonitrile (3i) was the most significant inhibitor for BChE (IC50 = 1.78 µM). In general, the inhibitory potency of compound 5 was weaker than the pure tacrine reference, and our findings may help to design and develop novel anticholinesterase drugs based on modified tacrines.

Hybridized 4-Trifluoromethyl-(1,2,3-triazol-1-yl)quinoline System: Synthesis, Photophysics, Selective DNA/HSA Bio-interactions and Molecular Docking.

The synthesis, structural analysis, and evaluation of the photophysical properties of twelve novel 2-aryl(heteroaryl)-6-(4-alkyl(aryl)-1H-1,2,3-triazol-1-yl)-4-(trifluoromethyl)quinolines (6-8), where aryl(heteroaryl)=Ph, 4-Me-C6 H4 , 4-F-C6 H4 and 2- furyl; 4-alkyl(aryl)=-CH2 OH, -(CH2 )5 CH3 and Ph, are reported. Hybrid scaffolds 6-8 were synthesized at 77-95 % yields by regioselective copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction of unpublished 6-azido-4-(trifluoromethyl)quinolines (2) with selected terminal alkynes (3-5). Azido intermediates 2 were obtained from the reaction of 6-amino-4-(trifluoromethyl)quinolines (1) and sodium azide at good yields (78-87 %). Compounds 6-8 were structurally fully characterized by 1 H-, 13 C- and 19 F- and 1 H-13 C 2D-NMR (HSQC, HMBC) spectroscopy, X-ray diffraction (SC-XRD) and HRMS analysis. Moreover, the photophysical properties, DNA- and HSA-binding experiments (bio-interactions), and molecular docking studies for compounds 6-8 were performed. These are discussed and compared with similar compounds from recent research.

Bromo-Substituted Diazenyl-pyrazolo[1,5-a]pyrimidin-2-amines: Sonogashira Cross-Coupling Reaction, Photophysical Properties, Bio-interaction and HSA Light-Up Sensor.

A convenient synthesis of a broad series of thirteen examples of alkyne-spacer derivatives 2 from the well-known Sonogashira cross-coupling reaction on diazenyl-pyrazolo[1,5-a]pyrimidin-2-amine compounds 1 is reported. The reactivity of heterocycles 1 due the presence of selected electron-donor (EDG) and electron-withdrawing (EWG) groups attached to different alkynes was evaluated. Also, the reactional versatility due the position variation of the bromo atom at the scaffolds 1 was also investigated. In general, derivatives presented strong absorption bands at the 250-500 nm optical window and UV to cyan emission properties. Also, the redox analysis was recorded by electrochemical cyclic voltammetry technique. For HSA biomacromolecule assays, spectroscopic studies by UV-Vis, steady-state and time-resolved emission fluorescence, and molecular docking calculations evidenced the ability of each compound to establish interactions with human serum albumin (HSA). Finally, the behavior presented for this new class of heterocycles makes them a promising tool as optical sensors for albumins.

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases.

A new series of ten examples of Schiff bases, namely (E)-2-(((2-alkyl(aryl/heteroaryl)-4-(trifluoromethyl)quinolin-6-yl)imino)methyl)phenols 3, was easily synthesized with yields of up to 91% from the reactions involving a series of 2-(R-substituted) 6-amino-4-(trifluoromethyl)quinolines 1 and 4(5)-R1-substituted salicylaldehydes 2 - in which alkyl/aryl/heteroaryl for 2-R-substituents are Me, Ph, 4-MeC6H4, 4-FC6H4, 4-NO2C6H4, and 2-furyl, and R1-substituents are 5-NEt2, 5-OCH3, 4-Br, and 4-NO2. Complementarily, the Schiff bases showed low to good quantum fluorescence yield values in CHCl3 (Φf = 0.12-0.80), DMSO (Φf = 0.20-0.75) and MeOH (Φf = 0.13-0.85). Higher values of Stokes shifts (SS) were observed in more polar solvents (DMSO; 65-150 nm and MeOH; 65-130 nm) than in CHCl3 (59-85 nm). Compounds 3 presented good stability under white-LED irradiation conditions and moderate ROS generation properties were observed.