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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

Taibi Ben Hadda, Zuhal Karagoz Genc, Vijay H. Masand, Nadia Nebbache, Ismail Warad, Shehdeh Jodeh, Murat Genc, Yahia N. Mabkhot, Assem Barakat, Hector Salgado Zamora

Abstract


A computational Petra/Osiris/Molinspiration/DFT(POM/DFT) based model has been developed for the identification of physic-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- antitumoractivity 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 x 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 (COd---NHd+) antitumor phramacophore site. 


Keywords


Cancer-Kinase (CK), antitumor agents, Ruthenium-Staurosporine complexes, DFT, Petra/Osiris/Molinspiration (POM) analyses

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DOI: http://dx.doi.org/10.17344/acsi.2015.1357

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Copyright (c) 2015 Taibi Ben Hadda, Zuhal Karagoz Genc, Vijay H. Masand, Nadia Nebbache, Ismail Warad, Shehdeh Jodeh, Murat Genc, Yahia N. Mabkhot, Assem Barakat, Hector Salgado Zamora

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