Synthesis and antimicrobial, acetylcholinesterase and butyrylcholinesterase inhibitory activities of novel ester and hydrazide derivatives of 3(2H)-pyridazinone

• Published in: Arzneimittel-Forschung Vol. 60; no. 7; pp. 452 - 458
• Main Authors: Ozcelik, Azime Berna, Gokce, Mehtap, Orhan, Ilkay, Kaynak, Fatma, Sahin, Mustafa Fethi
• Format: Journal Article
• Language: English
• Published: STUTTGART Thieme Medical Publishers 01.01.2010
• Subjects: Acetylcholinesterase - metabolism; Anti-Bacterial Agents - pharmacology; Antifungal Agents - pharmacology; Azides - pharmacology; Butyrylcholinesterase - metabolism; Candida - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Cholinesterase Inhibitors - pharmacology; Enterococcus faecalis - drug effects; Escherichia coli - drug effects; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Physical Sciences; Piperazines - pharmacology; Pseudomonas aeruginosa - drug effects; Science & Technology; Staphylococcus aureus - drug effects; Structure-Activity Relationship; ANTIPLATELET PROPERTIES; Antimicrobial activity; ANTIINFLAMMATORY ACTIVITY; 3(2H)-Pyridazinone-2-yl esters; ANALOGS; Butyrylcholinesterase inhibitors; ANTIFUNGAL ACTIVITY; Acetylcholinesterase inhibitors; 3(2H)-Pyridazinone-2-yl hydrazides; PYRIDAZINONE DERIVATIVES
• ISSN: 0004-4172; 1616-7066
• DOI: 10.1055/s-0031-1296311

In the current study, some novel ethyl 6-[(substituted-phenylpiperazine]-3(2H)-pyridazinone-2-yl propionate III and 6-[(substituted-phenylpiperazine]-3(2H)-pyridazinone-2-yl propionohydrazide IV derivatives were synthesized as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The structures of these new pyridazinone derivatives were confirmed by their IR, H-1-NMR spectra and elementary analysis. 6-Substituted-3(2H)-pyridazinone-2-yl propionate IIIa-e derivatives showed significant inhibitory activity against AChE and BChE. 6-[4-(3-Trifluoromethylphenyl)-piperazinel-3(2H)-pyridazinone-2-yl propionate IIIe has been found to be the most active compound in terms of inhibition of either AChE or BChE. Compound IIIe exhibited inhibitory activity close to that of galantamine (CAS 357-70-0) and did not show any selectivity between the two enzymes. Also the antimicrobial activities of III and IV derivatives have been evaluated. All III and IV derivatives exhibited poor antibacterial activities but moderate antifungal activities.