| Autor: |
Hadda TB, Genc ZK, Masand VH, Nebbache N, Warad I, Jodeh S, Genc M, Mabkhot YN, Barakat A, Salgado-Zamora H |
| Jazyk: |
angličtina |
| Zdroj: |
Acta chimica Slovenica [Acta Chim Slov] 2015; Vol. 62 (3), pp. 679-88. |
| DOI: |
10.17344/acsi.2015.1357 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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