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 (λ_em = 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.