Photoactive platinum(II) complexes of nonsteroidal anti-inflammatory drug naproxen: Interaction with biological targets, antioxidant activity and cytotoxicity

The effect on the therapeutic efficacy of Pt(II) complexes on combining non-steroidal anti-inflammatory drugs (NSAIDs) is an attractive strategy to circumvent chronic inflammation mediated by cancer and metastasis. Two square-planar platinum(II) complexes: [Pt(dach)(nap)Cl] (1) and [Pt(dach)(nap)(2)] (2), where dach = (1R,2R)-dichloro(cyclohexane-1,2-diamine) and NSAID drug naproxen (nap), have been designed for studying their biological activity. The naproxen bound to the Pt(II) centre get released upon photoirradiation with low-power UV-A light as confirmed by the significant enhancement in emission intensities of the complexes. The compounds were evaluated for their photophysical properties, photostability, reactivity with 5'-guanosine monophophosphate (5'-GMP), interactions with CT-DNA and BSA, antioxidant activity and reactive oxygen species mediated photo-induced DNA damage properties. ESI-MS studies demonstrated the formation of bis-adduct with 5'-GMP and the formation of Pt-II-DNA crosslinks by gel electrophoretic mobility shift assay and ITC studies. The interaction of the complexes I and 2 with the CT-DNA exhibits potential binding affinity (K-b similar to 10(4) M-1, K-app similar to 10(5) M-1), implying intercalation to CT-DNA through planar naphthyl ring of the complexes. Both the complexes also exhibit strong binding affinity towards BSA (K-BSA similar to 10(5) M-1). The complexes exhibit efficient DNA damage activity on irradiation at 365 nm via formation of singlet oxygen (O-1(2)) and hydroxyl radical ((OH)-O-center dot) under physiological conditions. Both the complexes were cytotoxic in dark and exhibit significant enhancement of cytotoxicity upon photo-exposure against HeLa and HepG2 cancer cells giving IC50 values ranging from 8 to 12 mu M for 1 and 2. The cellular internalization data showed cytosolic and nuclear localization of the complexes in the HeLa cells. (C) 2017 Elsevier Masson SAS. All rights reserved.