Synthesis and primary cytotoxicity evaluation of new 5-bromo-3-substituted-hydrazono-1H-2-indolinones.

In this study a new series of 5-bromo-3-[(3-substituted-5-methyl-4-thiazolidinone-2-ylidene)-hydrazono]-1H-2-indolinones (3a-i) and 5-bromo-3-[(2-thioxo-3-substituted-4, 5-imidazolidinedione-1-yl)imino]-1H-2-indolinones (4a-f) was synthesized by the cyclization of 5-bromo-3-(N-substituted-thiosemicarbazono)-1H-2-indolinones (2a-i)with ethyl 2-bromopropionate in anhydrous ethanolic medium and oxalyl cloride in anhydrous diethyl ether, respectively. Six compounds chosen as prototypes were evaluated in the 3-cell line, one dose in vitro primary cytotoxicity assay. Four of them were evaluated against the full panel of 60 human tumor cell lines at a minimum of five concentrations at 10-fold dilutions. Among the compounds tested, the 4-fluoro-phenylthiosemicarbazone derivative 2f showed the most favorable cytotoxicity. This compound demonstrated the most marked effects on a breast cancer cell line (BT-549, log(10)GI(50) value -6.40), a non small cell lung cancer cell line (NCI-H23, log(10)GI(50) value -6.10), and an ovarian cancer cell line (IGROV1, log(10)GI(50) value -6.02).