Pt and Ru complexes with biologically active ligandsтезисы доклада Тезисы

Работа с тезисами доклада


[1] Pt and ru complexes with biologically active ligands / Y. N. Nosova, I. A. Shutkov, I. V. Zenin et al. // Сборник тезисов 3-ей Российской конференции по медицинской химии. — Казань, 2017. — P. 24. Drug combination is widely applied in cancer chemotherapy and twin-drug approach is one of the lead technic in the modern drug discovery. Such design allows one to control activity and selectivity. Pt(IV) and Ru(III) complexes or Ru(II) organometallic compounds may be considered as a good scaffold for introduction of targeting ligand. The synthetic advantage of Pt(IV) complexes is the suitability for chemical modifications of axial positions. Ru(III) and Ru(II) compounds could be modified by coordination of bioactive ligands. Conjugation with such ligands can increase the activity or selectivity of new compounds and lead to controlled release of an active organic molecule into cancer cell. In this work three series of compounds with Pt(IV), Ru(III) and Ru(II) center with modified ligands were prepared. Glycolysis inhibitor lonidamine or retinoid X receptor agonist bexarotene were used as the bioactive organic moiety. Pt(IV) and Ru(II) compounds were characterized by 1D and 2D NMR (1H, 13C, 195Pt, 15N) spectroscopy. Structure and purity were proved by ESI-MS and elemental analysis. The antiproliferative activity of the all compounds was investigated against cancer cell lines (A549, SW480, MCF7). Several Pt(IV) complexes showed low micromolar in vitro activity (IC50 0.07÷11 μM) and notably more active than lonidamine, bexarotene and cisplatin. Highest potential showed Pt(IV) complexes with lonidamine (IC50 0.07÷2 μM) with tendency to nanomolar activity. Ru(III) complexes and Ru(II) compounds are more active than lonidamine and bexarotene, and less toxic than cisplatin and corresponding platinum compounds. For Ru(III) compounds with lonidamine-modified ligands increase of in vitro activity with linker lengthening was found (up to IC50 2÷10 μM). All the Ru(II) derivatives have relatively similar activity (IC50 23÷74 μM) which is not influenced by linker length.

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