Photoactive platinum(ii) β-diketonates as dual action anticancer agents

Abstract

Platinum(II) complexes, viz. [Pt(L)(cur)] (1), [Pt(L)(py-acac)] (2) and [Pt(L)(an-acac)] (3), where HL is 4,4′-bis-dimethoxyazobenzene, Hcur is curcumin, Hpy-acac and Han-acac are pyrenyl and anthracenyl appended acetylacetone, were prepared, characterized and their anticancer activities were studied. Complex [Pt(L)(acac)] (4) was used as a control. Complex 1 showed an absorption band at 430 nm (ε = 8.8 × 104 M−1 cm−1). The anthracenyl and pyrenyl complexes displayed bands near 390 nm (ε = 3.7 × 104 for 3 and 4.4 × 104 M−1 cm−1 for 2). Complex 1 showed an emission band at 525 nm (Φ = 0.017) in 10% DMSO–DPBS (pH, 7.2), while 2 and 3 were blue emissive (λem = 440 and 435, Φ = 0.058 and 0.045). There was an enhancement in emission intensity on glutathione (GSH) addition indicating diketonate release. The platinum(II) species thus formed acted as a transcription inhibitor. The released β-diketonate base showed photo-chemotherapeutic activity. The complexes photocleaved plasmid DNA under blue light of 457 nm forming ∼75% nicked circular (NC) DNA with hydroxyl radicals and singlet oxygen as the ROS. Complexes 1–3 were photocytotoxic in skin keratinocyte HaCaT cells giving IC50 of 8–14 μM under visible light (400–700 nm, 10 J cm−2), while being non-toxic in the dark (IC50: ∼60 μM). Complex 4 was inactive. Complexes 1–3 generating cellular ROS caused apoptotic cell death under visible light as evidenced from DCFDA and annexin-V/FITC-PI assays. This work presents a novel way to deliver an active platinum(II) species and a phototoxic β-diketone species to the cancer cells.