β-Maleimide substituted meso-arylporphyrins: Synthesis, transformations, physico-chemical and antitumor properties

Ol’shevskaya, V. A.; Alpatova, Victoria M.; Radchenko, A. Sh.; Ramonova, Alla A.; Petrova, Albina S.; Tatarskiy, Victor V.; Зайцев, А. В.; Kononova, Elena G.; Ikonnikov, Nikolay S.; Kostyukov, Alexey A.; Egorov, Anton E.; Moisenovich, Mikhail M.; Кузьмин, В. А.; Брагина, Н. А.; Shtil, Alexander А.

doi:10.1016/j.dyepig.2019.107760

Cited by 18 publications

(13 citation statements)

References 61 publications

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“…Importantly, NAC (1 mM) dramatically decreased cell survival in combination with 1 µg/mL CuO, the concentration that corresponds to ~IC 5 if added alone. Table 1 shows that the combination of CuO + NAC caused remarkable sensitization of all tested cell lines, including the sublines with molecular determinants of antitumor drug resistance, such as MDR 1/P-glycoprotein for K562/4 subline, anti-oxidative systems for SCOV3/CDDP subline, and an altered response to doxorubicin (Dox) due to p53 deficiency in the HCT116p53KO subline [ 24 , 25 ] (and the refs therein). Fold sensitization (determined as the ratio of IC 50CuO /IC 50CuO+NAC ) achieved values as high as 2–3 orders of magnitude ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Vulnerability to oxidative stress makes the plasma membrane (as well as membrane organelles) an attractive target for elimination of “intractable” tumor cells otherwise irresponsive to apoptotic stimuli [ 31 , 32 ]. We found that CuO NPs + NAC efficiently killed the K562/4 (P-glycoprotein mediated MDR), SCOV-3/CDDP (resistance to cisplatin; [ 24 ] and HCT116p53KO (altered response to DNA damaging agents; [ 25 ] sublines; the potency of the combination was similar among these sublines and their parental counterparts. However, non-malignant fibroblasts were sensitive to the combination of CuO NPs and NAC, indicating no cell-type selectivity of the combination.…”

Section: Discussionmentioning

confidence: 99%

“…Synthesis of the Cu complex of 2-(3′-maleimido)-5,10,15,20-tetraphenylporphyrin 6 and the metal free 2-(3′-maleimido)-5,10,15,20-tetraphenylporphyrin 7 has been reported in [ 24 ]. The copper complex of 5-[ p -(3′-maleimido)phenyl]-10,15,20-triphenylporphyrin; compound 8 ) was synthesized as follows: a solution of 50 mg (0.25 mmol) Cu(OAc) 2 ·H 2 O in methanol (5 mL) was added to a solution 50 mg (0.07 mmol) 5-[ p -(3′-maleimido)phenyl]-10,15,20-triphenylporphyrin 9 in methylene chloride (5 mL).…”

Section: Methodsmentioning

confidence: 99%

“…The panel of tumor cell lines included human K562, KU-812, and MOLM-6 chronic myelogenous leukemia; HCT116 colon, SKOV-3 ovarian, MCF-7, and MDA-MB-231 breast carcinomas; and B16F10 murine melanoma (all from American Type Culture Collection (Manassas, VA, USA)). In addition, the isogenic sublines with the molecular determinants of altered drug response were multidrug resistant MDR 1/P-glycoprotein overexpressing K562/4 subline, HCT116p53KO (non-functional p53) and SKOV-3/CDDP (a 4-fold resistance to cisplatin; gift of G.A.Posypanova, National Research Center ‘The Kurchatov Institute’, Moscow, Russia) [ 24 , 25 , 35 ]. Non-malignant hFB-hTERT6 skin fibroblasts were obtained via a lentiviral transduction of the full-length TERT gene under a cytomegalovirus promoter (gift of E. Dashinimaev, Engelhardt Institute of Molecular Biology, Moscow).…”

Section: Methodsmentioning

confidence: 99%

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Copper-Containing Nanoparticles and Organic Complexes: Metal Reduction Triggers Rapid Cell Death via Oxidative Burst

Tsymbal

Moiseeva

Agadzhanian

et al. 2021

IJMS

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Copper-containing agents are promising antitumor pharmaceuticals due to the ability of the metal ion to react with biomolecules. In the current study, we demonstrate that inorganic Cu2+ in the form of oxide nanoparticles (NPs) or salts, as well as Cu ions in the context of organic complexes (oxidation states +1, +1.5 and +2), acquire significant cytotoxic potency (2–3 orders of magnitude determined by IC50 values) in combinations with N-acetylcysteine (NAC), cysteine, or ascorbate. In contrast, other divalent cations (Zn, Fe, Mo, and Co) evoked no cytotoxicity with these combinations. CuO NPs (0.1–1 µg/mL) together with 1 mM NAC triggered the formation of reactive oxygen species (ROS) within 2–6 h concomitantly with perturbation of the plasma membrane and caspase-independent cell death. Furthermore, NAC potently sensitized HCT116 colon carcinoma cells to Cu–organic complexes in which the metal ion coordinated with 5-(2-pyridylmethylene)-2-methylthio-imidazol-4-one or was present in the coordination sphere of the porphyrin macrocycle. The sensitization effect was detectable in a panel of mammalian tumor cell lines including the sublines with the determinants of chemotherapeutic drug resistance. The components of the combination were non-toxic if added separately. Electrochemical studies revealed that Cu cations underwent a stepwise reduction in the presence of NAC or ascorbate. This mechanism explains differential efficacy of individual Cu–organic compounds in cell sensitization depending on the availability of Cu ions for reduction. In the presence of oxygen, Cu+1 complexes can generate a superoxide anion in a Fenton-like reaction Cu+1L + O2 → O2−.+ Cu+2L, where L is the organic ligand. Studies on artificial lipid membranes showed that NAC interacted with negatively charged phospholipids, an effect that can facilitate the penetration of CuO NPs across the membranes. Thus, electrochemical modification of Cu ions and subsequent ROS generation, as well as direct interaction with membranes, represent the mechanisms of irreversible membrane damage and cell death in response to metal reduction in inorganic and organic Cu-containing compounds.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Copper-Containing Nanoparticles and Organic Complexes: Metal Reduction Triggers Rapid Cell Death via Oxidative Burst

Tsymbal

Moiseeva

Agadzhanian

et al. 2021

IJMS

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“…The enhanced interest in these structures is related to the combinatorial effect of two functional blocks (boron-enriched and azaheterocyclic) in the same molecule cluster. The latter turns out to open additional opportunities for the practical use of these compounds in medicine, as well as in the design of promising photoluminescent materials and catalytic systems formed by transition metal complexes. In addition, the mutual influence of the carborane cage and certain azaheterocyclic fragments seems to promote adjustment of the useful optical properties in these species.…”

Section: Introductionmentioning

confidence: 99%

Cu(I)-Catalyzed Cycloaddition of Vinylacetylene ortho-Carborane and Arylazides in the Design of 1,2,3-Triazolyl-Modified Vinylcarborane Fluorophores

et al. 2020

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The methodology of Cu(I)-mediated 1,3-dipolar cycloaddition was first applied in the synthesis of photoactive 1,2,3-triazolylmodified vinylcarboranes of various architectures. As a result, a series of novel boron-enriched cluster compounds bearing a 1,2,3-triazol−vinyl− carborane conjugated system were synthesized in yields up to 92% and in mild reaction conditions. To reveal the "structure−luminescent properties" correlations attributed to the mutual influence of functional building blocks, the preliminary experiments on photophysical studies were carried out. The intramolecular charge transfer, as well as aggregation induced emission enhancement effects observed, could arouse a particular interest in these azaheterocyclic carboranes as challenging functional elements in the design of advanced materials for molecular electronics.

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S_NAr Reaction Toward the Synthesis of Fluorinated Quinolino[2,3,4‐at]porphyrins

2020

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An intramolecular S N Ar displacement of one o-fluorine atom of a meso-pentafluorophenyl-substituted porphyrin metal complex by a neighboring β-amino functionality generated the corresponding meso-fluorophenyl-substituted metallo-quinolino [2,3,4-at]porphyrins that are not accessible using established quinoline-annulation methodologies. The Cu(II), Ni(II), and Zn(II) complexes were thus prepared. The parent free base quinolino [2,3,4-at]porphyrin is accessible only by demetallation of the copper or zinc complexes. A strong through-space NMR-spectroscopic coupling between the remaining o-fluorine atoms on the annulated meso-aryl group and the β-hydrogen atom on the adjacent pyrrole moiety provide a clear spectroscopic signature for the annulation. Quinoline-annulation alters the optical properties significantly. On account of the presence of the β-amino functionality, all quinoline-annulated porphyrins show strong halochromic responses with Brønsted acids and bases, the prerequisite for their potential use in chemosensing applications.

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β-Maleimide substituted meso-arylporphyrins: Synthesis, transformations, physico-chemical and antitumor properties

Cited by 18 publications

References 61 publications

Copper-Containing Nanoparticles and Organic Complexes: Metal Reduction Triggers Rapid Cell Death via Oxidative Burst

Copper-Containing Nanoparticles and Organic Complexes: Metal Reduction Triggers Rapid Cell Death via Oxidative Burst

Cu(I)-Catalyzed Cycloaddition of Vinylacetylene ortho-Carborane and Arylazides in the Design of 1,2,3-Triazolyl-Modified Vinylcarborane Fluorophores

S_NAr Reaction Toward the Synthesis of Fluorinated Quinolino[2,3,4‐at]porphyrins

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β-Maleimide substituted meso-arylporphyrins: Synthesis, transformations, physico-chemical and antitumor properties

Cited by 18 publications

References 61 publications

Copper-Containing Nanoparticles and Organic Complexes: Metal Reduction Triggers Rapid Cell Death via Oxidative Burst

Copper-Containing Nanoparticles and Organic Complexes: Metal Reduction Triggers Rapid Cell Death via Oxidative Burst

Cu(I)-Catalyzed Cycloaddition of Vinylacetylene ortho-Carborane and Arylazides in the Design of 1,2,3-Triazolyl-Modified Vinylcarborane Fluorophores

SNAr Reaction Toward the Synthesis of Fluorinated Quinolino[2,3,4‐at]porphyrins

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Product

Resources

About

S_NAr Reaction Toward the Synthesis of Fluorinated Quinolino[2,3,4‐at]porphyrins