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were synthesized at 77-95 % yields by regioselective copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction of unpublished 6-azido-4-(trifluoromethyl)quinolines (2) with selected terminal alkynes (3-5).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.

Investigating ESIPT and donor-acceptor substituent effects on the photophysical and electrochemical properties of fluorescent 3,5-diaryl-substituted 1-phenyl-2-pyrazolines.

This paper describes the synthesis, structural study, and evaluation of electrochemical and photophysical properties by UV-Vis absorption and fluorescence emission analysis (solution and solid-state) of a series of eight 3,5-aryl-substituted 1-phenyl-2-pyrazolines (5), where 3-aryl = 2-OH-C6H4 (5a-g) or Ph (5h), and 5-aryl = Ph (a, h), 1-naphthyl (b), 4-Br-C6H4 (c), 4-F-C6H4 (d), 4-OCH3-C6H4(e), 4-NO2-C6H4 (f), 4-(N(CH3)2)-C6H4(g). The UV-Vis absorption properties of 2-pyrazolines were evaluated in DCM, MeCN, AcOEt, EtOH, and DMSO as the solvent and showed a fluorescence shift for the polar aprotic solvents. The steady-state fluorescence emission exhibited a band in the blue region when excited at the least energetic transition of each compound, although the excited-state intramolecular proton (ESIPT) effect was not detected. In the solid state, compounds presented similar behavior regarding absorption and emission properties compared to the solution assays. With the electrochemical analyses performed for the synthesized 2-pyrazolines, it was possible to conclude that the redox potentials were influenced by the electronic and steric effects of the substituents on the aryl rings and, according to the electronic nature of the substituents, which electron-donating groups were favored. Finally, the TD-DFT analyses revealed that all compounds had delocalized electron density throughout the 2-pyrazolines unit and were not influenced by the substituent bonded at C-5. Nonetheless, LUMO orbital analysis showed that only derivatives 5b and 5f have this localized density over the substituents.