DNA Binding and Catalytic Properties of Positively Charged Corroles

Gershman, Zoya; Goldberg, Israel; Gross, Zeev

doi:10.1002/anie.200700757

Cited by 87 publications

(60 citation statements)

References 39 publications

(22 reference statements)

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“…These tetrapyrrolic macrocycles with a direct linkage between two pyrrole units and with interesting physical and chemical properties are expected to play an important role in future medicinal applications [7e14]. For instance, metallocorroles with polar groups were disclosed as potent catalysts for the decomposition of peroxynitrite [10] and were also shown to have a large affinity to various proteins [12]. In fact a noncovalent assembly of corrole and a targeting protein, conferred promising cytotoxic and antitumor activities against a breast cancer cell line, mouse xenograft breast cancer model and towards human cancer cells [15e18].…”

Section: Introductionmentioning

confidence: 99%

Photodynamic effects induced by meso-tris(pentafluorophenyl)corrole and its cyclodextrin conjugates on cytoskeletal components of HeLa cells

Barata

Zamarrón

Neves

et al. 2015

European Journal of Medicinal Chemistry

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Section: Introductionmentioning

confidence: 99%

Photodynamic effects induced by meso-tris(pentafluorophenyl)corrole and its cyclodextrin conjugates on cytoskeletal components of HeLa cells

Barata

Zamarrón

Neves

et al. 2015

European Journal of Medicinal Chemistry

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“…Therefore the scavenging of ONOO − involves Mn(III) and O=Mn(IV) species with MnTBAP 3− and MnTSPP 3− and Mn(III) and O=Mn(V) species with corroles. 26,27 Thus far we have evidence that Mn(III)TBAP 3− can be reduced to Mn(II)TBAP 4− with biologically irrelevant dithionite [Batinic-Haberle et al , unpublished data]. Based on E. coli data para Mn(III) N -alkylpyridylporphyrins are in vivo associated/intercalated with nucleic acids, which makes them unavailable to the approach of O 2 ·− ; 2,4 therefore it is unlikely that they are involved in any other redox reactions to a large extent.…”

Section: Introductionmentioning

confidence: 99%

Methoxy-derivatization of alkyl chains increases the in vivo efficacy of cationic Mn porphyrins. Synthesis, characterization, SOD-like activity, and SOD-deficient E. coli study of meta Mn(iii) N-methoxyalkylpyridylporphyrins

et al. 2011

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Cationic Mn(III) N-alkylpyridylporphyrins (MnPs) are potent SOD mimics and peroxynitrite scavengers and diminish oxidative stress in a variety of animal models of central nervous system (CNS) injuries, cancer, radiation, diabetes, etc. Recently, properties other than antioxidant potency, such as lipophilicity, size, shape, and bulkiness, which influence the bioavailability and the toxicity of MnPs, have been addressed as they affect their in vivo efficacy and therapeutic utility. Porphyrin bearing longer alkyl substituents at pyridyl ring, MnTnHex-2-PyP5+, is more lipophilic, thus more efficacious in vivo, particularly in CNS injuries, than the shorter alkyl-chained analog, MnTE-2-PyP5+. Its enhanced lipophilicity allows it to accumulate in mitochondria (relative to cytosol) and to cross the blood-brain barrier to a much higher extent than MnTE-2-PyP5+. Mn(III) N-alkylpyridylporphyrins of longer alkyl chains, however, bear micellar character, and when used at higher levels, become toxic. Recently we showed that meta isomers are ~10-fold more lipophilic than ortho species, which enhances their cellular accumulation, and thus reportedly compensates for their somewhat inferior SOD-like activity. Herein, we modified the alkyl chains of the lipophilic meta compound, MnTnHex-3-PyP5+ via introduction of a methoxy group, to diminish its toxicity (and/or enhance its efficacy), while maintaining high SOD-like activity and lipophilicity. We compared the lipophilic Mn(III) meso-tetrakis(N-(6′-methoxyhexyl)-pyridinium-3-yl)porphyrin, MnTMOHex-3-PyP5+, to a hydrophilic Mn(III) meso-tetrakis(N-(2′-methoxyethyl)pyridinium-3-yl)porphyrin, MnTMOE-3-PyP5+. The compounds were characterized by uv-vis spectroscopy, mass spectrometry, elemental analysis, electrochemistry, and ability to dismute O2·−. Also, the lipophilicity was characterized by thin-layer chromatographic retention factor, Rf. The SOD-like activities and metal-centered reduction potentials for the MnIIIP/MnIIP redox couple were similar-to-identical to those of N-alkylpyridyl analogs: log kcat = 6.78, and E1/2 = +68 mV vs. NHE (MnTMOHex-3-PyP5+), and log kcat = 6.72, and E1/2 = +64 mV vs. NHE (MnTMOE-3-PyP5+). The compounds were tested in a superoxide-specific in vivo model: aerobic growth of SOD-deficient E. coli, JI132. Both MnTMOHex-3-PyP5+ and MnTMOE-3-PyP5+ were more efficacious than their alkyl analogs. MnTMOE-3-PyP5+ is further significantly more efficacious than the most explored compound in vivo, MnTE-2-PyP5+. Such a beneficial effect of MnTMOE-3-PyP5+ on diminished toxicity, improved efficacy and transport across the cell wall may originate from the favorable interplay of the size, length of pyridyl substituents, rotational flexibility (the ortho isomer, MnTE-2-PyP5+, is more rigid, while MnTMOE-3-PyP5+ is a more flexible meta isomer), bulkiness and presence of oxygen.

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“…Subsequent study was hampered by synthetic inaccessibility of corroles until 1999, when two new routes to the preparation of free base corrole were published by Paolesse 11 and Gross. 12,13 Over the next decade, a wealth of synthetic methodologies and variants were developed for synthesis of corroles, 14 with mesosubstituents, [15][16][17][18][19][20][21] various beta-substituents, [22][23][24][25][26] and eventually including both charged 27,28 and chiral 29 free-base corroles. The development of these organic syntheses is beyond the scope of this review, but the range of properties imparted by these synthetic options has greatly broadened the scope of applications of corroles.…”

Section: Introductionmentioning

confidence: 99%

Recent developments in out-of-plane metallocorrole chemistry across the periodic table

Buckley

Arnold

2015

Dalton Trans.

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DNA Binding and Catalytic Properties of Positively Charged Corroles

Cited by 87 publications

References 39 publications

Photodynamic effects induced by meso-tris(pentafluorophenyl)corrole and its cyclodextrin conjugates on cytoskeletal components of HeLa cells

Photodynamic effects induced by meso-tris(pentafluorophenyl)corrole and its cyclodextrin conjugates on cytoskeletal components of HeLa cells

Methoxy-derivatization of alkyl chains increases the in vivo efficacy of cationic Mn porphyrins. Synthesis, characterization, SOD-like activity, and SOD-deficient E. coli study of meta Mn(iii) N-methoxyalkylpyridylporphyrins

Recent developments in out-of-plane metallocorrole chemistry across the periodic table

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