Arylated Quinoline and Tetrahydroquinolines: Synthesis, Characterization and Their Metabolic Enzyme Inhibitory and Antimicrobial Activities

• Published in: ChemistrySelect (Weinheim) 2022-10, Vol.7 (37), p.n/a
• Main Authors: Koçyiğit, Ümit Muhammet, Ökten, Salih, Çakmak, Osman, Burhan, Gizem, Ataş, Mehmet, Taslimi, Parham, Gülçin, İlhami
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; Aryl quinoline and tetrahydroquinoline; Carbonic anhydrase; Enzymes inhibition; Suzuki-Miyura cross-coupling
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202203469

The aims of this study are to synthesize and characterize some new phenyl quinoline derivatives and to determine the activities of them and the recently prepared substituted phenyl quinolines against Acetylcholinesterase (AChE) and Charbonic anyhydrase (CA) enzymes and some microorganisms. The 6‐phenyl‐ (3a) and 6,8‐diphenyl‐(4a) tetrahydroquinolines were prepared by treatment of 6‐bromo and 6,8‐dibromo‐1,2,3,4‐tetrahydroquinoline with phenylboronic acids in the presence of Pd catalyze in high yields with respect to our reported procedure. Then, bromination of the 6‐phenyl‐ (3a) and 6,8‐diphenyl‐(4a) tetrahydroquinolines furnished novel 3‐bromo phenyl substituted quinolines 14 and 11 and 8‐bromo‐6‐pheyltetrahydroquinoline (13) in excellent yields (91, 99 and 92 %, respectively). Structures of all prepared compounds were characterized by 1H NMR,13C NMR, FTIR spectroscopy and elemental analysis. Both novel prepared and recent synthesized phenyl substituted tetrahydroquinolines and quinolines were screened for human carbonic anhydrase I, II isoenzymes (hCAs I and II) and AChE inhibitory and antimicrobial activities. Results indicated that all the synthetic compounds exhibited potent inhibitory activities against all targets as compared to the standard inhibitors, revealed by IC50 values. Ki values of novel substituted (trifluoromethoxy, thiomethyl and methoxy) phenyl quinolines 3a–d, 4a–c, 8–12, and 14 for hCA I, hCA II and AChE enzymes were obtained in the ranges 0.31–12.44, 0.92‐12.45, and 8.56–27.05 μM, respectively. Moreover, phenyl quinolines 3a–b, 10, 11, 14 displayed antifungal effect against yeasts in the range of 125–15.62 μg/mL. The study presents the anti‐Alzhemier activity, antiepileptic and antimicrobial activities of the currently and novel synthesized arylated tetrahydroquinolines and arylquinoline bromides against AChE, CA I and CAII enzymes, their inhibition activities against eight Gram (+), Gram (−) bacterial strains and yeasts. The results displayed that all aryl quinolines strongly inhibited AChE, CA I and CAII enzymes.