Photoactive platinum(II) beta-diketonates as dual action anticancer agents

Raza, Md Kausar and Mitra, Koushambi and Shettar, Abhijith and Basu, Uttara and Kondaiah, Paturu and Chakravarty, Akhil R (2016) Photoactive platinum(II) beta-diketonates as dual action anticancer agents. In: DALTON TRANSACTIONS, 45 (33). pp. 13234-13243.

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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 (epsilon = 8.8 x 10(4) M-1 cm(-1)). The anthracenyl and pyrenyl complexes displayed bands near 390 nm (epsilon = 3.7 x 10(4) for 3 and 4.4 x 10(4) M-1 cm(-1) for 2). Complex 1 showed an emission band at 525 nm (Phi = 0.017) in 10% DMSO-DPBS (pH, 7.2), while 2 and 3 were blue emissive (lambda(em) = 440 and 435, Phi = 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 beta-diketonate base showed photo-chemotherapeutic activity. The complexes photocleaved plasmid DNA under blue light of 457 nm forming similar to 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 mu M under visible light (400-700 nm, 10 J cm(-2)), while being non-toxic in the dark (IC50: similar to 60 mu M). 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 beta-diketone species to the cancer cells.

Item Type:	Journal Article
Publication:	DALTON TRANSACTIONS
Additional Information:	Copy right for this article belongs to the ROYAL SOC CHEMISTRY, THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	22 Oct 2016 09:16
Last Modified:	22 Oct 2016 09:16
URI:	http://eprints.iisc.ac.in/id/eprint/55000

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