Use of perfluorinated phosphines to provide thermomorphic anticancer complexes for heat-based tumor targeting.
A series of compounds of general formula [Ru(eta(6)-arene)(pta)(PR(3))Cl]BF(4) (arene = p-cymene or 4-phenyl-2-butanol; pta = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane, PR(3) = PPh(2)(p-C(6)H(4)C(2)H(4)C(8)F(17)), PPh(p-C(6)H(4)C(2)H(4)C(8)F(17))(2), P(p-C(6)H(4)C(2)H(4)C(6)F(13))(3), PPh(3) or P(p-C(6)H(4)F)(3)) have been prepared and characterized by spectroscopic methods. The structure of [Ru(eta(6)-p-cymene)(pta)Cl(P(p-C(6)H(4)F)(3))]BF(4) has also been established in the solid state by X-ray crystallography. The cytotoxicities of the compounds were determined in the A2780 and A2780 cisplatin-resistant cell lines revealing that the fluorinated phosphines significantly increase antiproliferative activity relative to their bis-chloride precursors. Two of the complexes were found to be thermoresponsive, that is, showing poor water solubility at 37 degrees C and good solubility at 42 degrees C, the temperature of a heated tumor, providing a method of tumor targeting. Incubation at 42 degrees C for 2 h resulted in improved cytotoxicities for two of the complexes.
Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
Anna K
AK
Renfrew
Rosario
R
Scopelliti
Paul J
PJ
Dyson
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D054879:Halogenation; D006358:Hot Temperature; D006801:Humans; D020128:Inhibitory Concentration 50; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010720:Phosphines / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry; D012995:Solubility; D014867:Water / Q000737:chemistry
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D010720:Phosphines; D014867:Water; D012428:Ruthenium