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Mirror‐Image Organometallic Osmium Arene Iminopyridine Halido Complexes Exhibit Similar Potent Anticancer Activity
Author(s) -
Fu Ying,
Soni Rina,
Romero María J.,
Pizarro Ana M.,
Salassa Luca,
Clarkson Guy J.,
Hearn Jessica M.,
Habtemariam Abraha,
Wills Martin,
Sadler Peter J.
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201302183
Subject(s) - chemistry , osmium , cisplatin , stereochemistry , medicinal chemistry , catalysis , combinatorial chemistry , biochemistry , biology , chemotherapy , ruthenium , genetics
Abstract Four chiral Os II arene anticancer complexes have been isolated by fractional crystallization. The two iodido complexes, ( S Os , S C )‐[Os(η 6 ‐ p ‐cym)(ImpyMe)I]PF 6 (complex 2 , ( S )‐ImpyMe: N ‐(2‐pyridylmethylene)‐( S )‐1‐phenylethylamine) and ( R Os , R C )‐[Os(η 6 ‐ p ‐cym)(ImpyMe)I]PF 6 (complex 4 , ( R )‐ImpyMe: N ‐(2‐pyridylmethylene)‐( R )‐1‐phenylethylamine), showed higher anticancer activity (lower IC 50 values) towards A2780 human ovarian cancer cells than cisplatin and were more active than the two chlorido derivatives, ( S Os , S C ) ‐ [Os(η 6 ‐ p ‐cym)(ImpyMe)Cl]PF 6 , 1 , and ( R Os , R C )‐[Os(η 6 ‐ p ‐cym)(ImpyMe)Cl]PF 6 , 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.