Pyrazole[3,4-d]pyridazine derivatives: Molecular docking and explore of acetylcholinesterase and carbonic anhydrase enzymes inhibitors as anticholinergics potentials
BIOORGANIC CHEMISTRY, cilt.92, 2019 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 92
- Basım Tarihi: 2019
- Doi Numarası: 10.1016/j.bioorg.2019.103213
- Dergi Adı: BIOORGANIC CHEMISTRY
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Index Chemicus (IC)
- Anahtar Kelimeler: Carbonic anhydrase, Enzyme inhibition, Computational studies, Molecular docking, GLUTATHIONE-S-TRANSFERASE, BIOLOGICAL EVALUATION, PYRAZOLE DERIVATIVES, CRYSTAL-STRUCTURE, BUTYRYLCHOLINESTERASE, ACID, LACTOPEROXIDASE, ANTIOXIDANT, FIPRONIL, SALTS
- Van Yüzüncü Yıl Üniversitesi Adresli: Evet
Özet
Recently, the pyridazine nucleus has been widely studied in the field of particular and new medicinal factors as drugs acting on the cardiovascular system. Additionally, a number of thienopyridazines have been claimed to possess interacting biological macromolecules and pharmacological activities such as NAD(P)H oxidase inhibitor, anticancer, and identified as a novel allosteric modulator of the adenosine A1 receptor. The literature survey demonstrates that coumarin, 1,2-pyrazole benzothiazole, and 1,3- thiazole scaffolds are the most versatile class of molecules. In this study, a series of substituted pyrazole[3,4-d]pyridazine derivatives (2a-n) were prepared, and their structures were characterized by Mass analysis, NMR, and FT-IR. These obtained pyrazole [3,4-d]pyridazine compounds were very good inhibitors of the carbonic anhydrase (hCA I and II) isoenzymes and acetylcholinesterase (AChE) with K-i values in the range of 9.03 +/- 3.81-55.42 +/- 14.77 nM for hCA I, 18.04 +/- 4.55-66.24 +/- 19.21 nM for hCA II, and 394.77 +/- 68.13-952.93 +/- 182.72 nM for AChE, respectively. The possible inhibition mechanism of the best-posed pyrazole[3,4-d]pyridazine and pyrazole-3-carboxylic acid derivatives and their interaction with catalytic active pocket residues were determined based on the calculations.