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Ortho Isomeric Mn(III) N-Alkyl- and Alkoxyalkylpyridylporphyrins-Enhancers of Hyaluronan Degradation Induced by Ascorbate and Cupric Ions.

Publication ,  Journal Article
Valachová, K; Rapta, P; Moura, NMM; Batinic-Haberle, I; Šoltés, L
Published in: Int J Mol Sci
August 10, 2021

High levels of hyaluronic acid (HA) in tumors correlate with poor outcomes with several types of cancers due to HA-driven support of adhesion, migration and proliferation of cells. In this study we explored how to enhance the degradation of HA into low-molecular fragments, which cannot prevent the immune system to fight tumor proliferation and metastases. The physiological solution of HA was exposed to oxidative degradation by ascorbate and cupric ions in the presence of either one of three ortho isomeric Mn(III) substituted N-alkyl- and alkoxyalkylpyridylporphyrins or para isomeric Mn(III) N-methylpyridyl analog, commonly known as mimics of superoxide dismutase. The changes in hyaluronan degradation kinetics by four Mn(III) porphyrins were monitored by measuring the alteration in the dynamic viscosity of the HA solution. The ortho compounds MnTE-2-PyP5+ (BMX-010, AEOL10113), MnTnBuOE-2-PyP5+ (BMX-001) and MnTnHex-2-PyP5+ are able to redox cycle with ascorbate whereby producing H2O2 which is subsequently coupled with Cu(I) to produce the •OH radical essential for HA degradation. Conversely, with the para analog, MnTM-4-PyP5+, no catalysis of HA degradation was demonstrated, due to its inertness towards redox cycling with ascorbate. The impact of different Mn(III)-porphyrins on the HA decay was further clarified by electron paramagnetic resonance spectrometry. The ability to catalyze the degradation of HA in a biological milieu, in the presence of cupric ions and ascorbate under the conditions of high tumor oxidative stress provides further insight into the anticancer potential of redox-active ortho isomeric Mn(III) porphyrins.

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Published In

Int J Mol Sci

DOI

EISSN

1422-0067

Publication Date

August 10, 2021

Volume

22

Issue

16

Location

Switzerland

Related Subject Headings

  • Superoxide Dismutase
  • Oxidation-Reduction
  • Metalloporphyrins
  • Magnesium
  • Hyaluronic Acid
  • Copper
  • Chemical Physics
  • Ascorbic Acid
  • 3404 Medicinal and biomolecular chemistry
  • 3107 Microbiology
 

Citation

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Valachová, K., Rapta, P., Moura, N. M. M., Batinic-Haberle, I., & Šoltés, L. (2021). Ortho Isomeric Mn(III) N-Alkyl- and Alkoxyalkylpyridylporphyrins-Enhancers of Hyaluronan Degradation Induced by Ascorbate and Cupric Ions. Int J Mol Sci, 22(16). https://doi.org/10.3390/ijms22168608
Valachová, Katarína, Peter Rapta, Nuno M. M. Moura, Ines Batinic-Haberle, and Ladislav Šoltés. “Ortho Isomeric Mn(III) N-Alkyl- and Alkoxyalkylpyridylporphyrins-Enhancers of Hyaluronan Degradation Induced by Ascorbate and Cupric Ions.Int J Mol Sci 22, no. 16 (August 10, 2021). https://doi.org/10.3390/ijms22168608.
Valachová K, Rapta P, Moura NMM, Batinic-Haberle I, Šoltés L. Ortho Isomeric Mn(III) N-Alkyl- and Alkoxyalkylpyridylporphyrins-Enhancers of Hyaluronan Degradation Induced by Ascorbate and Cupric Ions. Int J Mol Sci. 2021 Aug 10;22(16).
Valachová, Katarína, et al. “Ortho Isomeric Mn(III) N-Alkyl- and Alkoxyalkylpyridylporphyrins-Enhancers of Hyaluronan Degradation Induced by Ascorbate and Cupric Ions.Int J Mol Sci, vol. 22, no. 16, Aug. 2021. Pubmed, doi:10.3390/ijms22168608.
Valachová K, Rapta P, Moura NMM, Batinic-Haberle I, Šoltés L. Ortho Isomeric Mn(III) N-Alkyl- and Alkoxyalkylpyridylporphyrins-Enhancers of Hyaluronan Degradation Induced by Ascorbate and Cupric Ions. Int J Mol Sci. 2021 Aug 10;22(16).

Published In

Int J Mol Sci

DOI

EISSN

1422-0067

Publication Date

August 10, 2021

Volume

22

Issue

16

Location

Switzerland

Related Subject Headings

  • Superoxide Dismutase
  • Oxidation-Reduction
  • Metalloporphyrins
  • Magnesium
  • Hyaluronic Acid
  • Copper
  • Chemical Physics
  • Ascorbic Acid
  • 3404 Medicinal and biomolecular chemistry
  • 3107 Microbiology