Selected ferrocenyl chalcones as DNA/BSA-interacting agents and inhibitors of DNA topoisomerase I and II activity

• Published in: Journal of organometallic chemistry Vol. 861; pp. 1 - 9
• Main Authors: Konkoľová, Eva, Janočková, Jana, Perjési, Pál, Vašková, Janka, Kožurková, Mária
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.04.2018
• Subjects: Bovine serum albumin; Calf thymus DNA; Ferrocenyl chalcones; Spectroscopic techniques; Topoisomerases I a II; Spectroscopic techniques; Topoisomerases I a II; Bovine serum albumin; Ferrocenyl chalcones; Calf thymus DNA
• DOI: 10.1016/j.jorganchem.2018.01.031
• ISSN: 0022-328X

A series of four ferrocenyl chalcone derivatives (1-4) and one ferrocenyl non-chalcone derivative (5) were investigated with regards to their interactions with calf thymus DNA and bovine serum albumin (BSA). Study on the DNA/BSA interactive properties of complexes is one of the active subjects of bioorganic chemistry. It could provide fundamental data for developing potential therapeutic applications and understanding mechanism of action for drug. The interactions and binding characteristics of complexes with ctDNA and BSA were investigated using UV-Vis, CD and fluorescence spectroscopy. Moreover, topoisomerase inhibition assays were used to evaluate the ability of compounds to inhibit the activity of topoisomerases I/II. No interaction was detected between ctDNA and ferrocene derivatives. However, human topoisomerase I (hTOPI) was inhibited in a concentration-depend manner in the presence of compounds 1, 3, 4, although no inhibition was observed with compounds 2 and 5. In the case of human topoisomerase IIα, inhibition was observed and results indicate that these compounds can be classified as topoisomerase II suppressors, not poisons. The interaction between BSA and the four selected ligands (1-4) were studied by fluorescence quenching spectra. In addition, this method was used for the calculation of characteristic binding parameters. These results and results obtained by synchronous fluorescence spectra and 3D fluorescence spectra of the ferrocenyl chalcones with BSA determined that compounds create complexes with BSA and induce conformation changes. [Display omitted] •We studied new ferrocenyl chalcone derivatives.•The binding constants were determinate for ferrocenyl ligands - BSA (104 M−1).•Electrophoretic techniques proved that ligands 3 and 4 inhibited topo I (30 × 10−6 M).•Compounds 3 and 4 inhibited topoisomerse II activity at 5 × 10−6.