Evaluation of hydrazone and N-acylhydrazone derivatives of vitamin B6 and pyridine-4-carbaldehyde as potential drugs against Alzheimer’s disease

Bartolić, Marija; Matošević, Ana; Maraković, Nikola; Bušić, Valentina; Roca, Sunčica; Vikić-Topić, Dražen; Sabljić, Antonio; Bosak, Anita; Gašo-Sokač, Dajana (2024) Evaluation of hydrazone and N-acylhydrazone derivatives of vitamin B6 and pyridine-4-carbaldehyde as potential drugs against Alzheimer’s disease. Journal of Enzyme Inhibition and Medicinal Chemistry, 39 (1). ISSN 1475-6366

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Abstract

The growing prevalence of Alzheimer's disease calls for a drug that can simultaneously act towards several targets involved in the pathophysiology of the disease. In our study, we evaluated the potential of hydrazone and N-acylhydrazone derivatives of vitamin B6 and pyridine-4-carbaldehyde to be used as multi-target directed ligands targeting cholinergic system by inhibiting acetyl- and butyrylcholinesterase, lowering the accumulation of beta-amyloid plaques by inhibiting both the beta-secretase activity and amyloid self-aggregation, and maintaining the biometal balance by chelating certain biometals. Our results showed that all of the tested hydrazones were potent inhibitors of human cholinesterases with inhibition constants (Ki) in micromolar range able to lower the activity of beta-secretase, inhibit amyloid aggregation, chelate biometals and act as antioxidants. Also, most of them were estimated to be able to cross the blood-brain barrier by passive transport and to be absorbed in human intestines as well as with moderate metabolic stability in liver microsomes.

Item Type:	Article
Uncontrolled Keywords:	N-acylhydrazone; cholinesterase; amyloid self-aggregation; BACE1; chelation
Subjects:	NATURAL SCIENCES > Chemistry > Organic Chemistry BIOMEDICINE AND HEALTHCARE > Pharmacy > Medical Biochemistry
Divisions:	NMR Center
Projects:	Project title Project leader Project code Project type Razvoj bioaktivnih molekula za tretman neurodegenerativnih bolesti-BioMol4ND Dejan Opsenica; Sandra Šegan; Katarina Komatović; Anita Bosak IP-2020-02-9343 HRZZ Istraživačko-edukacijski centar za zdravstvenu i medicinsku ekologiju i zaštitu od zračenja – Rekonstrukcija i dogradnja Instituta za medicinska istraživanja i medicinu rada u Zagrebu- UNSPECIFIED KK.01.1.1.02.0007 EK
Depositing User:	Ema Buhin Šaler
Date Deposited:	27 Mar 2026 10:45
URI:	http://fulir.irb.hr/id/eprint/11518
DOI:	10.1080/14756366.2024.2431832

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