Wydział Chemii

Sandra Amanda Kozieł

Monika Katarzyna Lesiów

Daria Wojtala

Edyta Dyguda-Kazimierowicz

Dariusz Bieńko

Urszula Katarzyna Komarnicka

2021

Pharmaceuticals

14

685/1-685/25

10.3390/ph14070685

Naukowa

Angielski

Artykuł

A group of cytotoxic half-sandwich iridium(III) complexes with aminomethyl(diphenyl)phosphine derived from fluoroquinolone antibiotics exhibit the ability to (i) accumulate in the nucleus, (ii) induce apoptosis, (iii) activate caspase-3/7 activity, (iv) induce the changes in cell cycle leading to G2/M phase arrest, and (v) radicals generation. Herein, to elucidate the cytotoxic effects, we investigated the interaction of these complexes with DNA and serum proteins by gel electrophoresis, fluorescence spectroscopy, circular dichroism, and molecular docking studies. DNA binding experiments established that the complexes interact with DNA by moderate intercalation and predominance of minor groove binding without the capability to cause a double-strand cleavage. The molecular docking study confirmed two binding modes: minor groove binding and threading intercalation with the fluoroquinolone part of the molecule involved in pi stacking interactions and the Ir(III)-containing region positioned within the major or minor groove. Fluorescence spectroscopic data (HSA and apo-Tf titration), together with molecular docking, provided evidence that Ir(III) complexes can bind to the proteins in order to be transferred. All the compounds considered herein were found to bind to the tryptophan residues of HSA within site I (subdomain II A). Furthermore, Ir(III) complexes were found to dock within the apo-Tf binding site, including nearby tyrosine residue

arene iridium(III) complexes, fluoroquinolones, DNA-binding studies, protein-binding studies, drug delivery, reactive oxygen species

CC-BY

http://dx.doi.org/10.3390/ph14070685

http://www.mdpi.com/journal/metals