Synthesis Of 4-Substituted-3-Hydroxyquinolin-2(1h)-Ones With Anticancer Activity

Herein we show that the 3-hydroxyquinolin-2(1H)-one (3HQ) core is a suitable platform to develop new compounds with anticancer activity against MCF-7 (IC50 up to 4.82 mu M) and NCI-H460 (IC50 up to 1.8 mu M) cancer cell lines. The ring-expansion reaction of isatins with diazo esters catalysed by di-rhodium (II) complexes proved to be a simple and effective strategy to synthesize 4-carboxylate-3HQs (yields up to 92%). 4-Carboxamide-3HQs were more efficiently prepared using NHS-diazoacetate in yields up to 88%. This innovative methodology enabled the construction of "peptidic-like" 3HQs, with several amino acid substituents. Among this series, the L-leucine derivative induced the cell death of MCF-7 (IC50 of 15.1 mu M) and NCI-H460 (IC50 of 2.7 mu M) cancer cell lines without causing any appreciable cytotoxicity against the non-cancer cell model (CHOK1). (C) 2020 Elsevier Ltd. All rights reserved.