Synthesis and biological activity of some 2-imidazolinylhydrazone derivatives.
A series of N-(imidazolidin-2-ylidene)hydrazones and N-(4,5-dihydro-1H-imidazol-2-yl)-N-methylhydrazones were prepared and examined for alpha 1-, alpha 2-adrenergic and imidazoline I1, I2 receptors binding affinities as well as cytotoxic activity against human tumor cell lines. Among the compounds tested, 2-naphthaldehyde N-(imidazolidin-2-ylidene)hydrazone (3e) exhibited a significant affinity for both alpha 2-adrenergic and imidazoline I1 receptors (Ki = 94.3 nM and IC50 = 51.7 nM, respectively). Moreover, pyridine-2-carboxaldehyde N-(imidazolidin-2-ylidene)hydrazone (3l) showed the highest binding affinity to alpha 1-adrenoceptors (Ki = 24.6 nM), while quinoline-2-carboxaldehyde N-(imidazolidin-2-ylidene)hydrazone (3m) displayed the highest I2 affinity with a Ki value of 26.7 nM and a high selectivity with respect to alpha 2-adrenergic and imidazoline I1 receptors (Ki = 22470.0 nM and IC50 = 6145.0 nM, respectively). None of the tested N-(4,5-dihydro-1H-imidazol-2-yl)-N-methylhydrazones 4p-u displayed cytotoxic activity.
Kornicka
Anita
A
Department of Chemical Technology of Drugs, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland. a.kornicka@amg.gda.pl
Hudson
Alan L
AL
Bednarski
Patrick J
PJ
D045744:Cell Line, Tumor; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000494:pharmacology*; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D054755:Imidazoline Receptors / Q000187:drug effects / Q000378:metabolism; D020128:Inhibitory Concentration 50; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D006835:Hydrazones; D007093:Imidazoles; D054755:Imidazoline Receptors; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; C410887:imidazoline I1 receptors; C487767:imidazoline receptor 2