Mirror-Image Organometallic Osmium Arene Iminopyridine Halido Complexes Exhibit Similar Potent Anticancer Activity

作者：Fu Ying; Soni Rina; Romero Maria J; Pizarro Ana M; Salassa Luca; Clarkson Guy J; Hearn Jessica M; Habtemariam Abraha; Wills Martin; Sadler Peter J^*

来源：Chemistry - A European Journal, 2013, 19(45): 15199-15209.

DOI：10.1002/chem.201302183

• anticancer agents
• arene ligands
• chirality
• organometallic
• osmium

Four chiral Os-II arene anticancer complexes have been isolated by fractional crystallization. The two iodido complexes, (S-Os,S-C)-[Os((6)-p-cym)(ImpyMe)I]PF6 (complex 2, (S)-ImpyMe: N-(2-pyridylmethylene)-(S)-1-phenylethylamine) and (R-Os,R-C)-[Os((6)-p-cym)(ImpyMe)I]PF6 (complex 4, (R)-ImpyMe: N-(2-pyridylmethylene)-(R)-1-phenylethylamine), showed higher anticancer activity (lower IC50 values) towards A2780 human ovarian cancer cells than cisplatin and were more active than the two chlorido derivatives, (S-Os,S-C)-[Os((6)-p-cym)(ImpyMe)Cl]PF6, 1, and (R-Os,R-C)-[Os((6)-p-cym)(ImpyMe)Cl]PF6, 3. The two iodido complexes were evaluated in the National Cancer Institute 60-cell-line screen, by using the COMPARE algorithm. This showed that the two potent iodido complexes, 2 (NSC: D-758116/1) and 4 (NSC: D-758118/1), share surprisingly similar cancer cell selectivity patterns with the anti-microtubule drug, vinblastine sulfate. However, no direct effect on tubulin polymerization was found for 2 and 4, an observation that appears to indicate a novel mechanism of action. In addition, complexes 2 and 4 demonstrated potential as transfer-hydrogenation catalysts for imine reduction.

• 出版日期2013-11-4