Synthesis and biological activities of some new 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(p-substituted benzalhidrazone) derivatives

In this study 18 new 3(2H)-pyridazinone derivatives which are expected to show anticholinesterase and antimicrobial activities have been synthesized. Compounds have been synthesized starting from 3,6-dichloropyridazine. 6-[4-(3,4-Dichlorophenyl)piperazine-1-yl]-3(2H)-pyridazinone was obtained from hydrolysis of 3-chloro-6-[4-(3,4-dichlorophenyl)piperazine-1-yl]pyridazine which was synthesized by the reaction of 3,6-dichloropiridazine and 3,4-dichlorophenylpiperazine. Ester derivative was obtained from the reaction of the resulting lactam compound with ethyl bromoacetate. After that acetohydrazide derivative was contituted by reaxion of this ester derivative compound with hydrazinehydrat and the acetohydrazide were changed to title compounds which have benzalhydrazone structure by using substituted/nonsubstituted benzaldehydes. Yields, melting points, physical properties, values in thin-layer chromatography were determined. Their structures have been confirmed by IR, 1H-NMR, 13C-NMR and Mass spectral data. Anticholinesterase activity of the compounds was determined according to the Ellman's method in Gazi University Faculty of Pharmacy Department of Pharmacognosy. Compound 5f which is 3-methylbenzalhydrazone derivative and compound 5i which is 3-metoxibenzalhydrazone derivative were shown best AChE inhibitor affect in 100 µg/ml dose, % 75.52 inhibition of AChE and % 71.72 inhibition of AChE, respectively. Compound 5h which is 2-metoxibenzalhydrazone derivative and 5f were also best BChE inhibitor affect in 100 µg/ml dose, % 67.16 inhibition of BChE and % 62.03 inhibition of BChE, respectively. Antimicrobial activities of the compounds were also determined All of the synthesized compounds showed moderate antimicrobial activity. Antifungal activity of compounds were found more active than antibacterial activity. 5e (4-fluorobenzalhydrazone derivative) was choosen as best antibacterial (8-32 µg/ml) and antifungal (8 µg/ml) compound.