Mixed natural arylolefin-quinoline platinum(II) complexes: synthesis, structural characterization and in vitro cytotoxicity studies

Abstract

Five new platinum(II) complexes bearing a eugenol and a quinoline derivative, namely [η²-4-allyl-2-methoxy-1-(propoxycarbonylmethoxy)benzene]-trans-dichlorido(quinoline-κN)platinum(II), [PtCl₂(C₁₅H₂₀O₄)(C₉H₇N)], (2), {η²-4-allyl-2-methoxy-1-[(propan-2-yloxy)carbonylmethoxy]benzene}-trans-dichlorido(quinoline-κN)platinum(II), [PtCl₂(C₁₅H₁₉O₄)(C₉H₇N)], (3), [η²-4-allyl-2-methoxy-1-(propoxycarbonylmethoxy)benzene]chlorido(quinolin-8-olato-κ²N,O)platinum(II), [Pt(C₉H₆NO)Cl(C₁₅H₂₀O₄)], (4), {η²-4-allyl-2-methoxy-1-[(propan-2-yloxy)carbonylmethoxy]benzene}chlorido(quinolin-8-olato-κ²N,O)platinum(II), [Pt(C₉H₆NO)Cl(C₁₅H₂₀O₄)], (5), and [η²-4-allyl-2-methoxy-1-(propoxycarbonylmethoxy)benzene]chlorido(quinolin-2-carboxylato-κ²N,O)platinum(II), [Pt(C₁₀H₆NO₂)Cl(C₁₅H₂₀O₄)], (6), have been synthesized and fully characterized spectroscopically. A single-crystal X-ray diffraction study was carried out for complexes (2) and (4)-(6). PrEug [or 4-allyl-2-methoxy-1-(propoxycarbonylmethoxy)benzene] in (2), (4) and (6), and ⁱPrEug (the propan-2-yloxy analogue of PrEug) in (3) and (5) coordinate with Pt^II at the ethylenic double bond of the allyl group. In (2)-(6), the donor N atom of the amine group occupies a trans position with respect to the double bond. A comparison of the IC₅₀ values of 0.38-29.23 µM for (2)-(6) with cisplatin, as well as other platinum(II) complexes, indicates an excellent in vitro cytotoxicity against the KB, LU, Hep-G2 and MCF-7 cancer cell lines, with the highest cytotoxic effect (IC₅₀ = 0.38-1.99 µM) being for complexes (4) and (5) bearing a quinolin-8-olate ligand.

Keywords: anticancer activity; crystal structure; eugenol derivatives; platinum(II) complexes; quinoline.