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.
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.
authors.forename: Taibi Ben
authors.initials: TB
authors.lastname: Hadda
authors.forename: Zuhal K
authors.initials: ZK
authors.lastname: Genc
authors.forename: Vijay H
authors.initials: VH
authors.lastname: Masand
authors.forename: Nadia
authors.initials: N
authors.lastname: Nebbache
authors.forename: Ismail
authors.initials: I
authors.lastname: Warad
authors.forename: Shehdeh
authors.initials: S
authors.lastname: Jodeh
authors.forename: Murat
authors.initials: M
authors.lastname: Genc
authors.forename: Yahia N
authors.initials: YN
authors.lastname: Mabkhot
authors.forename: Assem
authors.initials: A
authors.lastname: Barakat
authors.forename: Hector
authors.initials: H
authors.lastname: Salgado-Zamora