Synthesis, DNA binding, and dual topoisomerase I/II inhibitory activities of [Ru(tpy)(adtpy)]2+ and [Ru(dtp)(adtpy)]2+

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Abstract

Two ruthenium (II) complexes [Ru(tpy)(adtpy)]²⁺(1) and [Ru(dtp)(adtpy)]²⁺(2) have been synthesized and characterized. The DNA-binding behaviors of complexes were studied by using spectroscopic and viscosity measurements. Results suggested that two complexes bind to DNA in an intercalative mode. Topoisomerase inhibition and DNA strand passage assay confirmed that two Ru (II) complexes acted as efficient dual inhibitors of topoisomerases I and II by interference with the DNA religation.. In MTT cytotoxicity studies, two Ru (II) complexes exhibited antitumor activity against BEL-7402, HeLa, MCF-7 and HepG2 tumor cells. Flow cytometry analysis shows an increase in the percentage of cells with apoptotic morphological features in the sub-G1 phase for Ru (II) complexes. Apoptosis induction has also been observed from AO/EB staining assay and Annexin V-FITC/PI Double Staining.