Synthesis, biological evaluation and molecular docking of novel pyrazole derivatives as potent carbonic anhydrase and acetylcholinesterase inhibitors

• Published in: Bioorganic chemistry 2019-05, Vol.86, p.420-427
• Main Authors: Turkan, Fikret, Cetin, Adnan, Taslimi, Parham, Karaman, Muhammet, Gulçin, İlhami
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; Acetylcholinesterase - metabolism; Animals; Carbonic anhydrase; Carbonic Anhydrase I - antagonists & inhibitors; Carbonic Anhydrase I - isolation & purification; Carbonic Anhydrase I - metabolism; Carbonic Anhydrase II - antagonists & inhibitors; Carbonic Anhydrase II - metabolism; Carbonic Anhydrase Inhibitors - chemical synthesis; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrase Inhibitors - pharmacology; Cholinesterase Inhibitors - chemical synthesis; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Dose-Response Relationship, Drug; Electrophorus; Enzyme inhibition; Humans; Molecular Docking Simulation; Molecular Structure; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Structure-Activity Relationship; Substituted pyrazole
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2019.02.013

[Display omitted] •A serie of novel pyrazole compounds (1–8 and 9a, b) was synthesised.•These precursors have been characterized by 1H and 13C NMR and FTIR spectroscopies.•Molecular docking studies of compounds (1–4) were obtained.•Their inhibition effects on hCA I, hCA II, and AChE enzymes were determined. A series of substituted pyrazole compounds (1–8 and 9a, b) were synthesized and their structure was characterized by IR, NMR, and Mass analysis. These obtained novel pyrazole derivatives (1–8 and 9a, b) were emerged as effective inhibitors of the cytosolic carbonic anhydrase I and II isoforms (hCA I and II) and acetylcholinesterase (AChE) enzymes with Ki values in the range of 1.03 ± 0.23–22.65 ± 5.36 µM for hCA I, 1.82 ± 0.30–27.94 ± 4.74 µM for hCA II, and 48.94 ± 9.63–116.05 ± 14.95 µM for AChE, respectively. Docking studies were performed for the most active compounds, 2 and 5, and binding mode between the compounds and the receptors were determined.