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- Title
Computational POM and DFT Evaluation of Experimental in-vitro Cancer Inhibition of Staurosporine-Ruthenium(II) Complexes: the Power Force of Organometallics in Drug Design.
- Authors
Hadda, Taibi Ben; Genc, Zuhal K.; Masand, Vijay H.; Nebbache, Nadia; Warad, Ismail; Jodeh, Shehdeh; Genc, Murat; Mabkhot, Yahia N.; Barakat, Assem; Salgado-Zamora, Hector
- 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 IC50 values (0.45 and 8 nM, respectively), superior to staurosporine derivative (pyridocarbazole ligand 1, 150 · 10³ nM). The IC50 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 (COδ--NHδ+) antitumor pharmacophore site.
- Subjects
DENSITY functional theory; STAUROSPORINE; RUTHENIUM; COMPLEX compounds; ORGANOMETALLIC chemistry; IN vitro studies; DRUG design
- Publication
Acta Chimica Slovenica, 2015, Vol 62, Issue 3, p679
- ISSN
1318-0207
- Publication type
Article
- DOI
10.17344/acsi.2015.1357