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

• Published in: Chembiochem : a European journal of chemical biology Vol. 23; no. 4; pp. e202100649 - n/a
• Main Authors: Kappenberg, Yuri G., Stefanello, Felipe S., Zanatta, Nilo, Martins, Marcos A. P., Nogara, Pablo A., Rocha, João B. T., Tisoco, Isadora, Iglesias, Bernardo A., Bonacorso, Helio G.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 16.02.2022; Wiley Subscription Services, Inc
• Subjects: Alkynes; Animals; Aromatic compounds; Biochemistry & Molecular Biology; Cattle; Chemical synthesis; Chemistry, Medicinal; Cycloaddition; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA binding; DNA biosynthesis; HAS binding; Humans; Intermediates; Life Sciences & Biomedicine; Molecular docking; Molecular Docking Simulation; NMR; Nuclear magnetic resonance; Organic compounds; Pharmacology & Pharmacy; Photochemical Processes; photophysical properties; Quinoline; Quinolines; Science & Technology; Serum Albumin, Human - chemistry; Sodium azide; Sodium azides; Spectroscopy; Structural analysis; DNA-BINDING; DESIGN; molecular docking; photophysical properties; HAS binding; CLICK CHEMISTRY; BIOLOGICAL EVALUATION; quinoline; DERIVATIVES; DNA binding
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.202100649

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‐C6H4, 4‐F‐C6H4 and 2‐ furyl; 4‐alkyl(aryl)=−CH2OH, −(CH2)5CH3 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were synthesized at 77–95 % yields by regioselective copper‐catalysed azide‐alkyne cycloaddition (CuAAC) reaction of unpublished 6‐azido‐4‐(trifluoromethyl)quinolines (2) with selected terminal alkynes (3–5).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 1H−, 13C− and 19F− and 1H−13C 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. Twelve novel hybridized 4‐trifluoromethyl‐(1,2,3‐triazol‐1‐yl)quinolines (6–8), were synthesized at 77–95 % yields by a regioselective copper‐catalysed azide‐alkyne cycloaddition (CuAAC), and characterized by NMR spectroscopy, and single‐crystal X‐ray diffraction (SC‐XRD) analysis. Subsequently, photophysical properties, BSA‐ and HSA‐binding experiments, and molecular docking studies for the new series 6–8 were performed. These are discussed, and compared with similar compounds from recent research.