Cholinesterases, α-glycosidase, and carbonic anhydrase inhibition properties of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives: Synthetic analogues for the treatment of Alzheimer's disease and diabetes mellitus

Bioorg Chem. 2020 Apr:97:103647. doi: 10.1016/j.bioorg.2020.103647. Epub 2020 Feb 1.

Abstract

In this study, using the Cu(OTf)2 catalyst, 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivative molecules were carried out in one step and with high yield (86-91%). The previously synthesized 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives, carbonic anhydrase I and II isozymes (hCA I and II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and α-glycosidase (α-Gly) enzymes with Ki values in the range of 4.88-15.94 nM for hCA I, 7.04-20.83 nM for hCA II, 68.25-158.27 for AChE, 60.17-91.27 for BChE and 0.36-2.36 nM for α-Gly, respectively. In silico studies were performed on the molecules inhibiting hCA I, hCA II, AChE, BChE and α-Gly receptors. When we evaluated the data obtained in this work, we determined the inhibition type of the 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives at the receptors. Reference inhibitors were used for all enzymes.

Keywords: 10-dione; 1H-pyrazolo[1, 2-b]phthalazine-5; Carbonic anhydrase; Cholinesterase; Molecular docking; α-glycosidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / metabolism
  • Glycoside Hydrolases / antagonists & inhibitors*
  • Glycoside Hydrolases / metabolism
  • Humans
  • Molecular Docking Simulation
  • Phthalazines / chemistry
  • Phthalazines / pharmacology*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*

Substances

  • Carbonic Anhydrase Inhibitors
  • Cholinesterase Inhibitors
  • Phthalazines
  • Pyrazoles
  • Glycoside Hydrolases