Knez, Damijan; Coquelle, Nicolas; Pislar, Anja; Zakelj, Simon; Jukic, Marko; Sova, Matej; Mravljak, Janez; Nachon, Florian; Brazzolotto, Xavier; Kos, Janko; Colletier, Jacques-Philippe; Gobec, Stanislav published their research in European Journal of Medicinal Chemistry on August 5 ,2018. The article was titled 《Multi-target-directed ligands for treating Alzheimer’s disease: Butyrylcholinesterase inhibitors displaying antioxidant and neuroprotective activities》.Computed Properties of C8H8N2O The article contains the following contents:
The limited clin. efficacy of current symptomatic treatment and minute effect on progression of Alzheimer’s disease has shifted the research focus from single targets towards multi-target-directed ligands. Here, a potent selective inhibitor of human butyrylcholinesterase was used as the starting point to develop a new series of multifunctional ligands. A focused library of derivatives was designed and synthesized that showed both butyrylcholinesterase inhibition and good antioxidant activity as determined by the DPPH assay. The crystal structure of compound 11 in complex with butyrylcholinesterase revealed the mol. basis for its low nanomolar inhibition of butyrylcholinesterase (Ki = 1.09±0.12 nM). In addition, compounds 8 and 11 show metal-chelating properties, and reduce the redox activity of chelated Cu2+ ions in a Cu-ascorbate redox system. Compounds 8 and 11 decrease intracellular levels of reactive oxygen species, and are not substrates of the active efflux transport system, as determined in Caco2 cells. Compound 11 also protects neuroblastoma SH-SY5Y cells from toxic Aβ1-42 species. These data indicate that compounds 8 and 11 are promising multifunctional lead ligands for treatment of Alzheimer’s disease. In the experiment, the researchers used 2-Methylimidazo[1,2-a]pyridin-8-ol(cas: 79707-11-2Computed Properties of C8H8N2O)
2-Methylimidazo[1,2-a]pyridin-8-ol(cas: 79707-11-2) belongs to imidazoles.Imidazole rings are part of unnatural cyclic peptides and are used as ester isosteres in peptidomimetic studies.
However, the application of imidazoles is not limited to the field of peptides and peptidomimetics. Computed Properties of C8H8N2O
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem