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Pyriplatin-Boron-Dipyrromethene Conjugates for Imaging and Mitochondria-Targeted Photodynamic Therapy

Raza, Md Kausar and Gautam, Srishti and Howlader, Prodip and Bhattacharyya, Arnab and Kondaiah, Paturu and Chakravarty, Akhil R (2018) Pyriplatin-Boron-Dipyrromethene Conjugates for Imaging and Mitochondria-Targeted Photodynamic Therapy. In: INORGANIC CHEMISTRY, 57 (22). pp. 14374-14385.

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Official URL: http://dx.doi.org/10.1021/acs.inorgchem.8b02546

Abstract

Monofunctional pyriplatin analogues cis-Pt(NH3)(2)(L)Cl](NO3) (1-3) having boron-dipyrromethene (BODIPY) pendants (L) with 1,3,5,7-tetramethy1-8-(4-pyridyl)-4,4'-difluoroboradiazaindacene moieties were designed and synthesized, and their photocytotoxic properties were studied. The Pt-BODIPY conjugates displayed an absorption band within 505-550 nm and a green emissive band near 535 nm in 1% DMSO/DMEM (Dulbecco's modified Eagle's medium) buffer. Complex cis-Pt(NH3)(2)(4-Me-py)Cl](NO3) (4) was used as a control for determining the structural aspects by X-ray crystallography. The mono- and diiodinated BODIPY complexes 2 and 3 showed generation of singlet oxygen on light activation as evidenced from the 1,3-diphenylisobenzofuran (DPBF) titration experiments. The cytotoxicity of the BODIPY complexes was tested against A549 (human lung cancer), MCF-7 (human breast cancer), and HaCaT (human skin keratinocyte) cells in dark and visible light (400-700 nm, 10 J cm(-2)). While complexes 2 and 3 showed excellent photocytotoxicity (IC50 approximate to 0.05 mu M), they remained essentially nontoxic in the dark (IC50 > 100 mu M). The emissive bands of 1 and 2 were used for cellular imaging by confocal microscopy study, which showed their mitochondria] localization. This was further supported by platinum estimation from isolated mitochondria and mitochondrial depolarization through a JC-1 assay. The photomediated apoptotic cell death was evidenced from flow cytometric assays, annexin-V/FITC-PI (fluorescein isothiocyanate-propidium iodide) and cell cycle arrest in sub-G1 and G2/M phases. The complexes bind to 9-ethylguanine as a model nucleobase to form monoadducts. A mechanistic study on DNA photocleavage activity using pUC19 DNA showed singlet oxygen as the reactive oxygen species (ROS). The combination of photodynamic therapy with DNA cross-linking property enhanced the anticancer potential of the monofunctional BODIPY-conjugates of pyriplatins.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to AMER CHEMICAL SOC
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Division of Chemical Sciences > Inorganic & Physical Chemistry
Depositing User: Id for Latest eprints
Date Deposited: 28 Dec 2018 05:35
Last Modified: 28 Dec 2018 05:39
URI: http://eprints.iisc.ac.in/id/eprint/61299

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