Reakcija β-amino-α,γ-dicianokrotononitrila s acetofenonom: sinteza derivata piridina, piridazina i tiofena s antimikrobnim djelovanjem

Condensation of β-amino-α,γ-dicyanocrotononitrile (1) with acetophenone gave the 2-amino-4-phenylpenta-1,3-diene-1,1,3-tricarbonitrile (2). The latter product was used in a series of heterocyclization reactions when react with different reagents like diazonium salts, hydrazines, hydroxylamine and elemental sulfur to give pyridazine, pyrazole, isoxazole and thiophene derivatives, respectively. On the other hand, it gave pyridine derivatives with aromatic aldehydes followed by reaction with cyanomethylene reagents. The MIC values for the newly synthesized product were measured against E. coli, B. cereus, B. subtilis and C. albicansKondenzacijom β-amino-α,γ-dicijanokrotononitrila 1 s acetofenonom dobiven je 2-amino-4-fenilpenta-1,3-dien-1,1,3-trikarbonitril (2) koji je upotrebljen u reakcijama heterociklizacije s različitim reagensima poput diazonijevih soli, hidrazina, hidroksilamina i elementarnog sumpora pri čemu su nastali derivati piridazina, pirazola, izoksazola, odnosno tiofena. Spoj 2 je u reakciji s aromatskim aldehidima te naknadno sa cijanometilenima dao derivate piridina. Određene su MIC vrijednosti za novosintetizirane spojeve protiv E. coli, B. cereus, B. subtilis i C. albicans

Synthesis, biological evaluation and molecular modeling of 1,2,3-triazole analogs of combretastatin A-1.

The synthesis, cytotoxicity, inhibition of tubulin polymerization data and anti-angiogenetic effects of seven 1,5-disubstituted 1,2,3-triazole analogs and two 1,4-disubstituted 1,2,3-triazole analogs of combretastatin A-1 (1) are reported herein. The biological studies revealed that the 1,5-disubstituted 1,2,3-triazoles 3-methoxy-6-(1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazol-5-yl)benzene-1,2-diol (6), 3-methoxy-6-(1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazol-5-yl)benzene-1,2-diamine (8) and 5-(2,3-difluoro-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazole (9) were the three most active compounds regarding inhibition of both tubulin polymerization and angiogenesis. Molecular modeling studies revealed that combretastatins 1 and 2 and analogs 5-11 could be successfully docked into the colchicine binding site of α,β-tubulin