Novel platinum(ii) complexes of 3-(aminomethyl)naphthoquinone Mannich bases: synthesis, crystal structure and cytotoxic activities

Abstract

The first examples of platinum(II) complexes of 3-(aminomethyl)naphthoquinone Mannich bases have been synthesised and their crystal structures are described. Neutral and charged complexes have been obtained, fully characterised and their cytotoxic activities have also been investigated. 3-[(R¹-amino)(pyridin-2-yl)methyl]-2-hydroxy-1,4-naphthoquinones (R¹ = n-Bu, HL1; Bn, HL2; furfuryl, HL3; n-heptyl, HL4 and n-decyl, HL5) coordinate to platinum(II) through the two nitrogen atoms. The neutral complexes cis-[Pt(HL)Cl₂] 1a–5a are analogous to cisplatin with the bidentate ligand HL and two chlorine atoms occupying cis positions. In the charged complexes cis-[Pt(L⁻)(NH₃)₂]NO₃1b–5b the deprotonated form of the ligand L⁻ also coordinates via the nitrogen atoms, and the other two positions around the platinum(II) ion are completed with NH₃ ligands. The cytotoxic activities of all compounds have been tested for six different cancer cell lines: MDA-MB-435 (melanoma), HL-60 (promyelocytic leukaemia), HCT-8 (colon), SF-295 (brain), OVCAR-8 (ovary) and PC-3 (prostate). Proligands HL4 and HL5 have exhibited high activity against HL-60 (IC₅₀ = 1.9 and 3.8 μmol L⁻¹, respectively), HCT-8 (IC₅₀ = 1.6 and 1.7 μmol L⁻¹, respectively) and SF-295 (IC₅₀ = 1.1 and 1.7 μmol L⁻¹, respectively). The chlorido complexes 1a–5a have shown high to moderate cytotoxic activities, complex 4a (R¹ = n-heptyl) being more active than proligand HL4 against melanoma (IC₅₀ = 6.4 and > 40 μmol L⁻¹, respectively) and more active than cisplatin against all tested cell lines. Among the amine charged complexes only 4b and 5b have exhibited significant cytotoxic activity against the tested cell lines, although they were only moderately active against the PC-3 cell line (IC₅₀ = 29.9 and 15.6 μmol L⁻¹, respectively). In general the compounds with the longest carbon chains (R¹ = n-heptyl and n-decyl) have exhibited the highest activities.