Synthesis and evaluation of cytotoxic activities of some substituted isoxazolone derivatives

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-substitude- 2,4-dihydro-3H-1,2,4-triazole-3-thiones (5a-c) were prepared from ethyl 4-aminobenzoate. 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 hydroxylamine 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-methyl- 4-[2-{4-[4-(4-alkyl/aryl)-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl] phenyl} hydrazinylidene] isoxazol-5(4H)-one (8f-g). The structures of the synthesized compounds were confirmed 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 inhibitions 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) hydrazinylidene] isoxazol-5(4H)-one (8a).