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, log10GI50 value —6.40), a non small cell lung cancer cell line (NCI‐H23, log10GI50 value —6.10), and an ovarian cancer cell line (IGROV1, log10GI50 value —6.02).