Ruthenium carbonyl containing 4-pyrones as potent anticancer agents

Four new triruthenium carbonyl containing 4-pyrones: Ru3(CO)8(2 L-2H) 1 (L = ethylmaltol), Ru3(CO)7(PTA) (2 L-2H) 2 (L = ethylmaltol, PTA = 1,3,5 triaza-7-phosphaadamantane), Ru3(CO)8(2 L-2H) 3 (L = allomaltol), Ru3(CO)7(PTA) (2 L-2H) 4 (L = allomaltol, PTA = 1,3,5 triaza-7-phosphaadamantane) have been synthesized and characterized. Anticancer activity of compounds 1–4 has been evaluated in vitro against five types of human cancer cell lines and compared with clinically used drug cisplatin. Anticancer activity of compound 1 is an order of magnitude more potent than cisplatin against five types of human cancer cell lines. Compounds 1 and 2 with ethyl group at 2-position is more active than the compounds 3 and 4 with methyl group at 6-position. Substitution of a CO ligand with PTA decreases the activity following the order 1 > 2 and 3 < 4. The single crystal X-ray structure of compound 1 shows two Ru-CH2-H2C-H---O-Ru interactions: ethyl group C (217)-C (218) of first ethylmaltolato ligand bonded to Ru (2) folded towards ruthenium Ru (3) to form Ru (2)-CH2-H2C-H--O-Ru (3) interaction and the second ethylmaltolato ligand C (317)-C (318) bonded to Ru (3) folded towards Ru (2) to form Ru (3)-CH2-H2C-H---O-Ru (2). Proton NMR shows a well-resolved multiplet instead of a simple quartet for methylene protons indicating asymmetric environment.