Details

Autor(en) / Beteiligte

• Santos, Daniela Corrêa
• Henriques, Ruan Roberto
• Junior, Marcos Antonio de Abreu Lopes
• Farias, André Borges
• Nogueira, Thayssa Lisboa do Couto
• Quimas, João Victor Fernandes
• Romeiro, Nelilma Correia
• Silva, Leandro Louback da
• Souza, Andréa Luzia Ferreira de

Titel

Acylhydrazones as isoniazid derivatives with multi-target profiles for the treatment of Alzheimer’s disease: Radical scavenging, myeloperoxidase/acetylcholinesterase inhibition and biometal chelation

Ist Teil von

• Bioorganic & medicinal chemistry, 2020-05, Vol.28 (10), p.115470-115470, Article 115470

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2020

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• [Display omitted] Acylhydrazones 1a-o, derived from isoniazid, were synthesized and evaluated for Myeloperoxidase (MPO) and Acetylcholinesterase (AChE) inhibition, as well as their antioxidant and metal chelating activities, with the purpose of investigating potential multi-target profiles for the treatment of Alzheimer’s disease. Synthesized compounds were tested using the 2,2-diphenyl-2-picrylhydrazyl (DPPH) method and 1i, 1j and 1 m showed radical scavenging ability. Compounds 1b, 1 h, 1i, 1 m and 1o inhibited MPO activity (10 μM) at 96.1 ± 5.5%, 90 ± 2.1%, 100.3 ± 1.7%, 80.1 ± 9.4% and 82.2 ± 10.6%, respectively, and only compound 1 m was able to inhibit 54.2 ± 1.7% of AChE activity (100 μM). Docking studies of the most potent compound 1 m were carried out, and the computational results provided the theoretical basis of enzyme inhibition. Furthermore, compound 1 m was able to form complexes with Fe2+ and Zn2+ ions in a 2:1 ligand:metal ratio according to the Job Plot method.