title: 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 × 10(4) M(-1) cm(-1)). The anthracenyl and pyrenyl complexes displayed bands near 390 nm (ε = 3.7 × 10(4) for 3 and 4.4 × 10(4) 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.
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India. arc@ipc.iisc.ernet.in.
authors.forename: Md Kausar
authors.initials: MK
authors.lastname: Raza
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India. arc@ipc.iisc.ernet.in.
authors.forename: Koushambi
authors.initials: K
authors.lastname: Mitra
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India. paturu@mrdg.iisc.ernet.in.
authors.forename: Abhijith
authors.initials: A
authors.lastname: Shettar
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India. arc@ipc.iisc.ernet.in.
authors.forename: Uttara
authors.initials: U
authors.lastname: Basu
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India. paturu@mrdg.iisc.ernet.in.
authors.forename: Paturu
authors.initials: P
authors.lastname: Kondaiah
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India. arc@ipc.iisc.ernet.in.
authors.forename: Akhil R
authors.initials: AR
authors.lastname: Chakravarty
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D004247:DNA / Q000187:drug effects; D053837:DNA Cleavage; D006801:Humans; D008027:Light; D010984:Platinum / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D010984:Platinum; D004247:DNA; C427203:calf thymus DNA; D003474:Curcumin