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

• A library of pyrazole-carboxylic acid derivatives were synthesized and fully characterized by spectral and analytical techniques. • Inhibition effects of the synthesized molecules against AChE and hCAs enzymes were investigated. • Novel molecules (5–27) were found as effective inhibitor molecules for the AChE, hCA I and hCA II enzymes. • In silico molecular docking computations were performed using autodock vina tool. • Most active compounds, 21 and 23 potently inhibit hCA I (PDB: 2CAB), hCA II (PDB: 5AML), and AChE (PDB: 1EVE) proteins. In this study, a library of novel alkyl arylamide, anhydride, diester, dinitrile and diketone derivatives of pyrazole-dicarboxylic acid were synthesized. The chemical structures of the compounds were elucidated by FT-IR, 1H NMR, 13C NMR and elemental analysis. These obtained pyrazole derivatives were evaluated to be highly potent inhibitors for acetylcholinesterase (AChE) and carbonic anhydrases (hCAs). Synthesized novel compounds (5–27) were found to be effective inhibitor molecules for the AChE, hCA I and hCA II enzymes. K i values in the range of 7.76–53.78 nM for AChE, 11.27–50.31 nM for hCA I and 9.97–36.22 nM for hCA II. According to the docking results, it was seen that the molecules which we examined were able to inhibit the relevant targets quite successfully. Furthermore, it was found that the in silico estimated K i values were very compatible with the experimental data. In the last section, the compounds' (for ligands 21 and 23) ADME characteristics were examined. [Display omitted] [ABSTRACT FROM AUTHOR]