1,3-Dioxoindan-2-carboxamides as Bioactive Ligand Scaffolds for the Development of Novel Organometallic Anticancer Drugs

Abstract

A series of novel 1,3-dioxoindan-2-carboxamide-based complexes were synthesized, designed to employ both the attributes of half-sandwich complexes and the topoisomerase inhibiting properties of the ligand scaffold. The compounds were characterized with standard analytical methods. Their stability in aqueous systems and the impact of either the metal center or the ligand scaffold on the affinity toward small biomolecules such as amino acids, DNA model compounds, and small proteins were determined by IT-ESI mass spectrometry. The cytotoxicity was investigated in three human cancer cell lines by means of a colorimetric MTT assay, and preliminary structure–activity relationships were derived. The benzyl derivatives showed the highest in vitro activity and promising topoisomerase IIα inhibition in the range of the IC₅₀ values. In addition, the induced changes in the cell cycle distribution were determined and the apoptosis induction potential elucidated