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Computational POM and DFT Evaluation of Experimental in-vitro Cancer Inhibition of Staurosporine-Ruthenium(II) Complexes: the Power Force of Organometallics in Drug Design

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Tue, 2015-10-27 16:03 — Ismail Warad
Journal Title, Volume, Page: 
Acta Chim. Slov. 2015, 62
Year of Publication: 
2015
Authors: 
Taibi Ben Hadda, Ismail Warad, 1 1, * Zuhal K. Genc, 5 Shehdeh Jodeh, Assem Barakat 7 2, 5 * Vijay H. Masand, Murat Genc, 6 Hadda et al.: Computational POM and DFT Evaluation ... 3 Nadia Nebbache, Yahia N. Mabkhot, and Hector Salgado-Zamora
Preferred Abstract (Original): 
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
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+
50 
) antitumor pharmacophore site.