Back to Search
Start Over
Design and synthesis of a DNA intercalative half-sandwich organoruthenium(<scp>ii</scp>)–chromone complex: cytotoxicity evaluation and topoisomerase Iα inhibition assay
- Source :
- New Journal of Chemistry. 43:5475-5487
- Publication Year :
- 2019
- Publisher :
- Royal Society of Chemistry (RSC), 2019.
-
Abstract
- In the present study, we report the molecular design and synthesis of [Ru(η6-p-cymene)-(chromone)Cl] complex (1) as a potential topoisomerase I inhibitor. The structural elucidation of complex 1 was carried out by analytical, spectral and single crystal X-ray crystallographic techniques. Complex 1 crystallized in the monoclinic Pc space group with a Ru(II) ion coordinated to a p-cymene arene unit in a usual “piano-stool” geometry. In vitro binding interaction studies of complex 1 with ct-DNA and HSA were carried out and suggested a strong binding affinity towards DNA via an intercalative mode. DNA photocleavage activity was carried out with a pBR322 plasmid DNA substrate to ascertain the cleaving ability and the mechanistic pathway of the cleavage process. Topoisomerase I inhibition assay of complex 1 was performed via gel electrophoresis which revealed a significant inhibitory effect on the enzyme catalytic activity at a minimum concentration of 20 μM. Molecular docking studies of the complex were carried out with DNA, HSA and topoisomerase I to determine the specific binding preferences at the target site and complement the spectroscopic studies. Cytotoxic studies of complex 1 on a series of five human cancer cell lines, viz. A-498, HepG2, HeLa, MCF-7 and MIA-PA-CA-2, by the SRB assay revealed a moderate but selective activity towards pancreatic and cervical cancer cell lines.
- Subjects :
- Gel electrophoresis
biology
Stereochemistry
Topoisomerase
02 engineering and technology
General Chemistry
Topoisomerase-I Inhibitor
010402 general chemistry
021001 nanoscience & nanotechnology
biology.organism_classification
01 natural sciences
Catalysis
0104 chemical sciences
HeLa
chemistry.chemical_compound
chemistry
Chromone
Materials Chemistry
biology.protein
A-DNA
0210 nano-technology
Cytotoxicity
DNA
Subjects
Details
- ISSN :
- 13699261 and 11440546
- Volume :
- 43
- Database :
- OpenAIRE
- Journal :
- New Journal of Chemistry
- Accession number :
- edsair.doi...........5baf6ad74b66fdcbc837cda427760310