6533b7d7fe1ef96bd1267c3e

RESEARCH PRODUCT

DNA-binding and in vitro cytotoxic activity of platinum(II) complexes of curcumin and caffeine

Luís Korrodi-gregórioValentina CensiPatrick GamezMarta Pérez-hernándezPiero MastrorilliVanessa Soto-cerratoMaria Michela Dell'annaRicardo Pérez-tomásAna B. Caballero

subject

PhotoactivationCurcuminCytotoxicityIntercalation (chemistry)chemistry.chemical_elementCaffeine; Curcumin; Cytotoxicity; DNA interaction; Natural ligands; Photoactivation; Platinum(II) complexAntineoplastic Agents010402 general chemistryLigands01 natural sciencesBiochemistryMedicinal chemistryNucleobaseInorganic Chemistrychemistry.chemical_compoundDrug StabilityCoordination ComplexesCaffeineCell Line TumorMoietyMoleculeAnimalsHumansPlatinumMolecular Structure010405 organic chemistryDNA0104 chemical sciencesDNA interactionchemistryCurcuminPlatinum(II) complexCattleCaffeine Curcumin Cytotoxicity DNA interaction Natural ligands Photoactivation Platinum(II) complexCisplatinDrug Screening Assays AntitumorSelectivityPlatinumNatural ligandsCis–trans isomerism

description

Abstract Three Pt(II) complexes containing the natural ligands curcumin and caffeine, namely [Pt(curc)(PPh3)2]Cl (1), [PtCl(curc)(DMSO)] (2) (curc = deprotonated curcumin) and trans-[Pt(caffeine)Cl2(DMSO)] (3), were synthesized and fully characterized. The data obtained suggest that, for both 1 and 2, the anion of curcumin is coordinated to the platinum ion via the oxygen atoms of the β-diketonate moiety. Spectroscopic features reveal that in 2 and 3, a DMSO molecule is S-bonded to the metal centre. For 3, all data indicate a square-planar geometry formed by a 9-N bonded caffeine, two trans chloride anions and a DMSO. The three complexes undergo changes in solution upon incubation for 24 h; 1 and 2 release curcumin while 3 isomerizes from trans to cis configuration. The DNA-binding and cytotoxic properties of 1–3 were evaluated in vitro. Despite their structural similarity, curcuminate-containing 1 and 2 exhibit distinct DNA interactions. While 1 appears to intercalate between nucleobase pairs, inducing the oxidative degradation of the biomolecule, 2 behaves as a groove binder, by means of electrostatic forces. Caffeine-containing 3 exhibits a behaviour that is comparable to that of 2. Complexes 1 and 2 showed moderate to high cytotoxicity and selectivity against several cancer cell lines, while 3 is inactive. Compounds 1 and 2 can be further activated by visible-light irradiation.

yearjournalcountryeditionlanguage
2019-01-01
10.1016/j.jinorgbio.2019.110749https://hdl.handle.net/10447/584150