Synthesis and evaluation of cytotoxic activities of some substituted isoxazolone derivatives

Abstract

Several isoxazolone derivatives were synthesized, starting from substituted 1,3,4-thiadiazoles and 1,2,4-triazole-3-thione. In the first part of the research, compounds 2-(4-aminophenyl)-5-alkyl/arylamino-1,3,4-thiadiazoles (4a-e) and 5-(4-aminophenyl)-4-sub- stitude-2,4-dihydro-3H-1,2,4-triazole-3-thiones (5a-c) were prepared from ethyl 4-aminoben- zoate. In the second part, compounds, which were prepared by coupling the diazonium salts of aromatic primary amines with ethyl acetoacetat (6a-e, 7a-c) were cyclized with hydroxy- lamine hydrochloride and sodium acetate in ethanol and yielded 3-methyl-4-(2-{4-(5 alkyl/ arylamino)-1,3,4-thiadiazol-2-yl)phenyl} hydrazinylidene)isoxazol-5(4H)-one (8a-e) 3-me- thyl-4-(2-{4-(4-(4-alkyl/aryl)-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)phenyl}hydrazinyli- dene)isoxazol-5(4H)-one (8f-g). The structures of the synthesized compounds were con- firmed by elemental analysis (C,H,N,S), UV, IR, 1H-NMR and mass spectroscopic methods. Cytotoxicity of these compounds were evaluated by using HEK293 cell line of MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) assay. The highest inhibi- tions were confirmed as %45.72 for the compound 3-methyl-4-(2-(4-{5-((4-methoxyphenyl) amino)-1,3,4-thiadiazol-2-yl}phenyl)hydrazinylidene)isoxazol-5(4H)-one (8e) and %33.07 for the compound 3-methyl-4-(2-(4-{5-((4-methylphenyl)amino)-1,3,4-thiadiazol-2-yl}phenyl)hy- drazinylidene)isoxazol-5(4H)-one (8a).