Prospectives on Ruthenium anticancer agents are encouraging since Ru(II) can directly interact on tumor cells via multiple mechanisms provoking their death. The selection of ligands plays a key role in anticancer activity, the addition of hydrophobic species such as PPh3 to a metal center increases drug uptake in cancer cells and could allow the intercalation in DNA nucleobases pairs. Metallodrugs often show an enhanced anticancer activity compared to free ligands. In this context, ligands with well-established antitumor activity as 7- and (R)-9-Hydroxy stearic acid (HSA) were selected and reacted with mer-[Ru(H)2(CO)(PPh3)3] to give Ru(II) anticancer species.2 The anticancer in vitro properties of this class of metallo-prodrugs could be ascribed to synergistic effects between the metal center and bioactive ligands. The results have been compared with the analogously coordinated innocuous 12-HSA. The three novel Ru(II)-HSA complexes were fully characterized spectroscopically by using ESI-MS, IR, UV-Vis, and NMR techniques. The nature of Ru-12-HSA was also determined by single crystal X-ray diffraction, Cytotoxicity, cell proliferation, and DNA damage tests were performed demonstrating the biological activity of Ru-7-HSA and Ru-9-HSA.
“Synthesis and Antiproliferative study of Ru(II) – Hydroxy Stearic Acids ”
Giacomo Drius;Silvia Bordoni;Magda Monari;Carla Boga;Gabriele Micheletti;Natalia Calonghi
2023
Abstract
Prospectives on Ruthenium anticancer agents are encouraging since Ru(II) can directly interact on tumor cells via multiple mechanisms provoking their death. The selection of ligands plays a key role in anticancer activity, the addition of hydrophobic species such as PPh3 to a metal center increases drug uptake in cancer cells and could allow the intercalation in DNA nucleobases pairs. Metallodrugs often show an enhanced anticancer activity compared to free ligands. In this context, ligands with well-established antitumor activity as 7- and (R)-9-Hydroxy stearic acid (HSA) were selected and reacted with mer-[Ru(H)2(CO)(PPh3)3] to give Ru(II) anticancer species.2 The anticancer in vitro properties of this class of metallo-prodrugs could be ascribed to synergistic effects between the metal center and bioactive ligands. The results have been compared with the analogously coordinated innocuous 12-HSA. The three novel Ru(II)-HSA complexes were fully characterized spectroscopically by using ESI-MS, IR, UV-Vis, and NMR techniques. The nature of Ru-12-HSA was also determined by single crystal X-ray diffraction, Cytotoxicity, cell proliferation, and DNA damage tests were performed demonstrating the biological activity of Ru-7-HSA and Ru-9-HSA.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
