Abstract
A computational Petra/Osiris/Molinspiration/DFT(POM/DFT) based model has been developed for the identification of physico-chemical parameters governing the bioactivity of ruthenium-staurosporine complexes 2-4 containing an antitumoral-kinase (TK) pharmacophore sites. The four compounds 1-4 analyzed here were previously screened for their antitumor activity, compounds 2 and 4 are neutral, whereas analogue compound 3 is a monocation with ruthenium(II) centre. The highest anti- antitumor activity was obtained for compounds 3 and 4, which exhibited low IC(50) values (0.45 and 8 nM, respectively), superior to staurosporine derivative (pyridocarbazole ligand 1, 150 · 10(3) nM). The IC(50) of 3 (0.45 nM), represents 20,000 fold increased activity as compared to staurosporine derivative 1. The increase of bioactivity could be attributed to the existence of pi-charge transfer from metal-staurosporine to its (CO(δ)--NH(δ+)) antitumor pharmacophore site.
Highlights
Staurosporine derivatives (Figure 1) have been thoroughly studied in organic and inorganic chemistry
This study proved that a simple control of nature of simple coordination to non-toxic transition metals leads to compounds with high activities and reduced cytotoxicities of staurosporine as parent and clinical standard drug
Tumor inhibition of kinase through staurosporine ligand and its complexes was elucidated by means of density functional theory (DFT)-derived reactivity indexes
Summary
Staurosporine derivatives (Figure 1) have been thoroughly studied in organic and inorganic chemistry. Other studies on the interaction between Pd(II) and Pt(II) complexes of small molecules and DNA has been the focus of similar recent research in the scope of life science, chemistry, clinical medicine and genetics.[7,8] These studies are very useful for investigating the structure and biological function of DNA, kinases and elucidating the damage mechanism of DNA but Ru(II) complexes are less toxic than other transition metal complexes. For this reason we focalize all our attention on Ru-staurosporine complexes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
