Cyclopalladated and cycloplatinated benzophenone imines: Antitumor, antibacterial and antioxidant activities, DNA interaction and cathepsin B inhibition

The antitumor, antibacterial and antioxidant activity, DNA interaction and cathepsin B inhibition of cyclo-ortho-palladated and -platinated compounds [Pd(C,N)](2)(mu-X)(2) [X = OAc (1), X = Cl (2)] and trans-N,P-[M(C,N)X(PPh3)] [M = Pd, X = OAc (3), M = Pd, X = Cl (4), M = Pt, X = Cl (5)] are discussed [(C,N) = cyclo-ortho-metallated benzophenone imine]. The cytotoxicity of compound 5 has been evaluated towards human breast (MDA-MB-231 and MCF-7) and colon (HCT-116) cancer cell lines and that of compounds 1-4 towards the HCT-116 human colon cancer cell line. These cytotoxicities have been compared with those previously reported for compounds 1-4 towards MDA-MB-231 and MCF-7 cancer cell lines. Compound 3 and 4 were approximately four times more active than cisplatin against the MDA-MB-231 and MCF-7 cancer cell lines, and compound 5, was approximately four times more potent than cisplatin against the HCT-116 cancer cell line. The antibacterial activity of compounds 1-5 was in between the ranges of activity of the commercial antibiotic compounds cefixime and roxithromycin. Complexes 1-2 and 4-5 presented also antioxidant activity. Compounds 1-5 alter the DNA tertiary structure in a similar way to cisplatin, but at higher concentration, and do not present a high efficiency as cathepsin B inhibitors. Compound 5 has not been previously described, and its preparation, characterization, and X-ray crystal structure are reported. (C) 2014 Elsevier Inc. All rights reserved.