NDLI: Photoactive platinum(II) β-diketonates as dual action anticancer agents

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Basu, Uttara Mitra, Koushambi Chakravarty, Akhil R. Shettar, Abhijith Raza, Md Kausar Kondaiah, Paturu
Description	Author Affiliation: Raza MK ( Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India. arc@ipc.iisc.ernet.in.); Mitra K ( Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India. arc@ipc.iisc.ernet.in.); Shettar A ( Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India. paturu@mrdg.iisc.ernet.in.); Basu U ( Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India. arc@ipc.iisc.ernet.in.); Kondaiah P ( Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India. paturu@mrdg.iisc.ernet.in.); Chakravarty AR ( Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India. arc@ipc.iisc.ernet.in.)
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 $(λ_{em}$ = 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 $IC_{50}$ of 8–14 μM under visible light (400–700 nm, 10 J $cm^{−2}),$ while being non-toxic in the dark $(IC_{50}:$ ∼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.
ISSN	14779226
Issue Number	33
Journal	Dalton Trans.
Volume Number	45
e-ISSN	13645447
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2016-08-16
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Chemistry
Content Type	Text
Resource Type	Article
Subject	Inorganic Chemistry

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in