Tetra(3,4-pyrido)porphyrazines Caught in the Cationic Cage: Toward Nanomolar Active Photosensitizers

0467049 - ÚFCH JH 2017 RIV US eng J - Journal Article
Macháček, M. - Demuth, J. - Čermák, P. - Vavrečková, M. - Hrubá, L. - Jedličková, A. - Kubát, Pavel - Šimůnek, T. - Nováková, V. - Zimčík, P.
Tetra(3,4-pyrido)porphyrazines Caught in the Cationic Cage: Toward Nanomolar Active Photosensitizers.
Journal of Medicinal Chemistry. Roč. 59, č. 20 (2016), s. 9443-9456. ISSN 0022-2623. E-ISSN 1520-4804
Institutional support: RVO:61388955
Keywords : TARGETED PHOTODYNAMIC THERAPY * SINGLET OXYGEN * PHOTOPHYSICAL PROPERTIES
Subject RIV: CF - Physical ; Theoretical Chemistry
Impact factor: 6.259, year: 2016

Investigation of a series of tetra(3,4-pyrido)porphyrazines (TPyPzs) substituted with hydrophilic substituents revealed important structure activity relationships for their use in photodynamic therapy (PDT). Among them, a cationic TPyPz derivative with total of 12 cationic charges above, below and in the plane of the core featured a unique spatial arrangement that caught the hydrophobic core in a cage, thereby protecting it fully from aggregation in water. This derivative exhibited exceptionally effective photodynamic activity on a number of tumor cell lines (HeLa, SK-MEL-28, A549, MCF-7) with effective concentrations (EC50) typically below 5 nM, at least an order of magnitude better than the EC50 values obtained for the clinically approved photosensitizers verteporfin, temoporfin, protoporphyrin IX, and trisulfonated hydroxyaluminum phthalocyanine. Its very low dark toxicity (TC50 > 400 mu M) and high ability to induce photo damage to endothelial cells (EA.hy926) without preincubation suggest the high potential of this cationic TPyPz derivative in vascular-targeted PDT.
Permanent Link: http://hdl.handle.net/11104/0265192