BODIPY-based Ru(II) and Ir(III) organometallic complexes of avobenzone, a sunscreen material: Potent anticancer agents

Gupta, Gajendra; Cherukommu, Shirisha; Srinivas, G.; Lee, Seon Woong; Mun, Sung Hwan; Jung, Jaehoon; Nagesh, Narayana; Lee, Chang Yeon

doi:10.1016/j.jinorgbio.2018.08.009

Cited by 48 publications

(11 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ruthenium compounds have shown varied preferential localization in different cellular compartments and organelles, mostly in nuclear, lysosomal, and mitochondrial compartments. Intracellular localization studies with ruthenium compounds that incorporate BODIPY ligands in their structure have been reported, ,− as well as studies to assess cellular uptake . Ruthenium(II) p -cymene compounds with chelating O,O and N,O ligands containing BODIPY have accumulated preferentially in mitochondria, while with pyridine and bipyridyl BODIPY-modified ligands, accumulation in both mitochondria and the endoplasmic reticulum was observed.…”

Section: Resultsmentioning

confidence: 99%

“…Intracellular localization studies with ruthenium compounds that incorporate BODIPY ligands in their structure have been reported, ,− as well as studies to assess cellular uptake . Ruthenium(II) p -cymene compounds with chelating O,O and N,O ligands containing BODIPY have accumulated preferentially in mitochondria, while with pyridine and bipyridyl BODIPY-modified ligands, accumulation in both mitochondria and the endoplasmic reticulum was observed. Metallorectangles based on ruthenium(II) p -cymene derivatives with BODIPY-modified polypyridyl ligands were shown to have different preferential accumulation in cellular compartments depending on the type of cancer cell line .…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Intracellular Localization Studies of the Luminescent Analogue of an Anticancer Ruthenium Iminophosphorane with High Efficacy in a Triple-Negative Breast Cancer Mouse Model

et al. 2021

View full text Add to dashboard Cite

The potential of ruthenium(II) compounds as an alternative to platinum-based clinical anticancer agents has been unveiled after extensive research for over 2 decades. As opposed to cisplatin, ruthenium(II) compounds have distinct mechanisms of action that do not rely solely on interactions with DNA. In a previous report from our group, we described the synthesis, characterization, and biological evaluation of a cationic, water-soluble, organometallic ruthenium(II) iminophosphorane (IM) complex of p-cymene, ([(η6-p-cymene)Ru{(Ph3PN-CO-2N-C5H4)-κ-N,O}Cl]Cl (1 or Ru-IM), that was found to be highly cytotoxic against a panel of cell lines resistant to cisplatin, including triple-negative breast cancer (TNBC) MDA-MB-231, through canonical or caspase-dependent apoptosis. Studies on a MDA-MB-231 xenograft mice model (after 28 days of treatment) afforded an excellent tumor reduction of 56%, with almost negligible systemic toxicity, and a favored ruthenium tumor accumulation compared to other organs. 1 is known to only interact weakly with DNA, but its intracellular distribution and ultimate targets remain unknown. To gain insight on potential mechanisms for this highly efficacious ruthenium compound, we have developed two luminescent analogues containing the BOPIPY fluorophore (or a modification) in the IM scaffold with the general structure of [(η6-p-cymene)Ru{(BODIPY-Ph2PN-CO-2-NC5H4)-κ-N,O}Cl]Cl {BODIPY-Ph2P = 8-[(4-diphenylphosphino)phenyl]-4,4-dimethyl-1,3,5,7-tetramethyl-2,6-diethyl-4-bora-3a,4a-diaza-s-indacene (3a) and 4,4-difluoro-8-[4-[[2-[4-(diphenylphosphino)benzamido]ethyl]carbamoyl]phenyl]-1,3,5,7-tetramethyl,2,6-diethyl-4-bora-3a,4a-diaza-s-indacene (3b)}. We report on the synthesis, characterization, lipophilicity, stability, luminescence properties, and cell viability studies in the TNBC cell line MDA-MB-231, nonmalignant breast cells (MCF10a), and lung fibroblasts (IMR-90) of the new compounds. The ruthenium derivative 3b was studied by fluorescence confocal microscopy. These studies point to a preferential accumulation of the compound in the endoplasmic reticulum, mitochondria, and lysosomes. Inductively coupled plasma optical emission spectrometry (ICP-OES) analysis also confirms a greater ruthenium accumulation in the cytoplasmic fraction, including endoplasmic reticulum and lysosomes, and a smaller percentage of accumulation in mitochondria and the nucleus. ICP-OES analysis of the parent compound 1 indicates that it accumulates preferentially in the mitochondria and cytoplasm. Subsequent experiments in 1-treated MDA-MB-231 cells demonstrate significant reactive oxygen species generation.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Intracellular Localization Studies of the Luminescent Analogue of an Anticancer Ruthenium Iminophosphorane with High Efficacy in a Triple-Negative Breast Cancer Mouse Model

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The dipyridine-functionalized BODIPY ligands were synthesized using methods described previously . All other reagents were commercially obtained and used without further purification.…”

Section: Methodsmentioning

confidence: 99%

“…19 More recently, Lee et al introduced dipyridyl BODIPY ligands for the synthesis of self-assembled ruthenium and iridium metalla-rectangles for anticancer applications. 20−24 Furthermore, Nitschke et al developed several BODIPY-based metal supramolecules with sensing, host–guest, and other interesting physical properties. 25−27 Although several BODIPY ligands have been used to develop metal-based supramolecules, macrocycles based on palladium or platinum metals have been rarely reported.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, pyridine-functionalized BODIPY ligands were introduced by Hupp et al to develop metal–organic frameworks with interesting light-harvesting properties . More recently, Lee et al introduced dipyridyl BODIPY ligands for the synthesis of self-assembled ruthenium and iridium metalla-rectangles for anticancer applications. − Furthermore, Nitschke et al developed several BODIPY-based metal supramolecules with sensing, host–guest, and other interesting physical properties. − Although several BODIPY ligands have been used to develop metal-based supramolecules, macrocycles based on palladium or platinum metals have been rarely reported. Pistolis et al designed the first BODIPY-based platinum macrocycles with a square architecture that exhibited interesting physical properties .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Heterometallic BODIPY-Based Molecular Squares Obtained by Self-Assembly: Synthesis and Biological Activities

et al. 2019

Self Cite

View full text Add to dashboard Cite

Metal-based multinuclear supramolecules with different functionalities designed by self-assembly represent a growing area of research due to their versatile applications, particularly as anticancer agents. Four novel boron dipyrromethene (BODIPY)-based octacationic heterometallic molecular squares, 3–6 were synthesized by self-assembly via reaction of dipyridyl BODIPY ligands with suitable 90° palladium and platinum acceptors. The formation of the as-synthesized molecular squares was confirmed by multinuclear NMR spectroscopy, elemental analysis, high resolution electrospray mass spectrometry, UV–vis spectroscopy, and fluorescence spectroscopy. The square molecular structures of 4 and 6 were further rationalized theoretically using the PM7 semi-empirical method. The activities of the supramolecules against cancer cells were tested using cell lines of various malignant and nonmalignant origins. Complexes 3–6 showed high cytotoxicity toward cancer cells but 7.0 to 15.2 times lower cytotoxic effects were observed against nonmalignant human kidney epithelial cells (HEK-293). Particularly, complexes 3–6 provided 2.1–6.0 times lower IC 50 values as compared to cisplatin in HCT116 cells. Interestingly, BDP ligand-containing complexes ( 3 and 4 ) induced cytotoxicity through apoptosis, whereas BDPCC-based complexes ( 5 and 6 ) induced cell death by necrosis. This study presents a novel series of iron-based heteroatomic palladium and platinum complexes that exhibit substantial potential as drug candidates for anticancer therapy.

show abstract

Cytotoxic dimeric half‐sandwich Ru(II), Os(II) and Ir(III) complexes containing the 4,4′‐biphenyl‐based bridging ligands

Štarha

Hošek

Trávnı́ček

et al. 2020

Applied Organom Chemis

View full text Add to dashboard Cite

A series of dinuclear half‐sandwich Ru(II), Os(II) and Ir(III) complexes [Ru2(μ‐Ln)(η6‐pcym)2Cl2](PF6)2 (1, 4), [Os2(μ‐Ln)(η6‐pcym)2Cl2](PF6)2 (2, 5) and [Ir2(μ‐Ln)(η5‐Cp*)2Cl2](PF6)2 (3, 6), based on 4,4′‐biphenyl‐based bridging Schiff base ligands N,N′‐(biphenyl‐4,4′‐diyldimethylidyne)bis‐2‐(pyridin‐2‐yl)methanamine (L1; for 1–3) and N,N′‐(biphenyl‐4,4′‐diyldimethylidyne)bis‐2‐(pyridin‐2‐yl)ethanamine (L2; for 4–6) is reported; pcym = 1‐methyl‐4‐(propan‐2‐yl)benzene, Cp* = pentamethylcyclopentadienyl. The complexes were characterized by relevant analytical techniques (i.e. elemental analysis, FT‐IR, NMR, ESI‐MS), and their in vitro cytotoxicity was assessed at six cancerous and two non‐cancerous (healthy) human cell lines. Overall, complexes 4–6, containing the L2 bridging ligand, revealed higher cytotoxicity as compared with 1–3 and, thus, they were studied in greater detail. The best‐performing complex 6 exceeded at least twice the in vitro cytotoxicity of cisplatin and showed high selectivity towards the cancer cells over the normal ones, including the primary culture of human hepatocytes. In contrast to cisplatin, complexes 4–6 did not induce the cell cycle modification of the treated A2780 human ovarian carcinoma cells (studied by flow cytometry and Western blot analysis). High levels of superoxide anion were induced by complexes 4–6 at the A2780 cells. The levels of activated forms of Caspase‐3 and Caspase‐8 at the A2780 cells treated by Ru(II) complex 4 were comparable with cisplatin, while complexes 5 and 6 had only a minor effect on activation of these caspases.

show abstract

BODIPY-based Ru(II) and Ir(III) organometallic complexes of avobenzone, a sunscreen material: Potent anticancer agents

Cited by 48 publications

References 69 publications

Intracellular Localization Studies of the Luminescent Analogue of an Anticancer Ruthenium Iminophosphorane with High Efficacy in a Triple-Negative Breast Cancer Mouse Model

Intracellular Localization Studies of the Luminescent Analogue of an Anticancer Ruthenium Iminophosphorane with High Efficacy in a Triple-Negative Breast Cancer Mouse Model

Heterometallic BODIPY-Based Molecular Squares Obtained by Self-Assembly: Synthesis and Biological Activities

Cytotoxic dimeric half‐sandwich Ru(II), Os(II) and Ir(III) complexes containing the 4,4′‐biphenyl‐based bridging ligands

Contact Info

Product

Resources

About