Mitochondria‐Targeted Anticancer Activity of BODIPY‐Appended Iron(III) Catecholates in Red Light. Issue 35 (18th December 2017)

• Record Type: Journal Article
• Authors: Garai, Aditya; Pant, Ila; Bhattacharyya, Arnab; Kondaiah, Paturu; Chakravarty, Akhil R.
• Is Part Of: ChemistrySelect. Volume 2:Issue 35(2017)
• Page Start: 11686
• Page End: 11692
• Publication Date: 2017-12-18
• Subjects: Bioinorganic Chemistry -- BODIPY -- Iron -- Mitochondrial localization -- Photodynamic therapy; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201702166
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: Iron(III) catecholates of dipicolylamine (dpa) bases having appended Benzyl (in bzdpa) or BODIPY (borondipyrromethene) moiety (in L 1 and L 2 ), viz. [Fe(Bzdpa)(cat)Cl] (1 ), [Fe(L 1 )(cat)Cl] (2 ) and [Fe(L 2 )(cat)Cl] (3 ), were prepared and characterized (H2 cat=catechol). The iron(III) complexes with a ligand‐to‐metal charge transfer (LMCT) band within 600–800 nm were studied for their photocytotoxicity in visible (400–700 nm) and red (600–720 nm) light. Complex2 with a BODIPY fluorophore in L 1 gave IC50 values of 2.2±0.5 and 15.0±0.7 μM in visible and red light, respectively, in HeLa cells. Complex3 with a diiodo‐BODIPY moiety showed excellent PDT activity giving respective IC50 values of 0.8±0.2 and 12.6±1.1 μM. They are less toxic in dark (IC50 : ≥85 μM). A similar activity was observed in MCF‐7 cancer cells. The BODIPY complexes showed significant mitochondrial localization. Annexin FITC assay showed apoptotic cell death involving reactive oxygen species (ROS). Photo‐generation of ROS was evidenced from dichlorofluorescein diacetate (DCFDA) assay. Mechanistic studies on DNA photocleavage reactions showed the presence of two types of ROS. Singlet oxygen formation from BODIPY was evidenced from the 1, 3‐diphenylisobenzofuran (DPBF) experiments. Hydroxyl radical was generated on red light photo‐activation of the LMCT band within photodynamic therapy (PDT) spectral window. Abstract : A mitochondria‐localizing iron(III) catecholate complex having a diiodo‐BODIPY moiety as a near‐IR light photosensitizer showed remarkable photodynamic therapy (PDT) effect in HeLa and MCF‐7 cancer cells in red light of 600–720 nm giving IC50 values of 12–20 μM and apoptotic cell death by hydroxyl radicals and singlet oxygen as the ROS, while being essentially non‐toxic (IC50 : >100 μM) in dark.