1,3-Dioxoindan-2-carboxamides as Bioactive Ligand
Scaffolds for the Development of Novel Organometallic Anticancer Drugs
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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
IC<sub>50</sub> values. In addition, the induced changes in the cell
cycle distribution were determined and the apoptosis induction potential
elucidated