Assessment of Some Unsymmetrical Porphyrins as Promising Molecules for Photodynamic Therapy of Cutaneous Disorders
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Published:2023-12-29
Issue:1
Volume:17
Page:62
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ISSN:1424-8247
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Container-title:Pharmaceuticals
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language:en
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Short-container-title:Pharmaceuticals
Author:
Burloiu Andreea Mihaela1, Manda Gina2ORCID, Lupuliasa Dumitru1, Socoteanu Radu Petre3, Mihai Dragos Paul1ORCID, Neagoe Ionela Victoria2, Anghelache Laurentiu-Iliuta2ORCID, Surcel Mihaela2, Anastasescu Mihai3ORCID, Olariu Laura4, Gîrd Cerasela Elena1ORCID, Barbuceanu Stefania Felicia1ORCID, Ferreira Luis Filipe Vieira5ORCID, Boscencu Rica1
Affiliation:
1. Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia St., 020956 Bucharest, Romania 2. “Victor Babeş” National Institute of Pathology, 050096 Bucharest, Romania 3. “Ilie Murgulescu” Institute of Physical Chemistry, Romanian Academy, 060021 Bucharest, Romania 4. “SC. Biotehnos SA”, 3-5 Gorunului St., 075100 Bucharest, Romania 5. BSIRG—Biospectroscopy and Interfaces Research Group, iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal
Abstract
In order to select for further development novel photosensitizers for photodynamic therapy in cutaneous disorders, three unsymmetrical porphyrins, namely 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.2), 5-(2-hydroxy-5-methoxyphenyl)-10,15,20-tris-(4-carboxymethylphenyl) porphyrin (P3.2), and 5-(2,4-dihydroxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P4.2), along with their fully symmetrical counterparts 5,10,15,20-tetrakis-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.1) and 5,10,15,20-tetrakis-(4-carboxymethylphenyl) porphyrin (P3.1) were comparatively evaluated. The absorption and fluorescence properties, as well as atomic force microscopy measurements were performed to evaluate the photophysical characteristics as well as morphological and textural properties of the mentioned porphyrins. The cellular uptake of compounds and the effect of photodynamic therapy on the viability, proliferation, and necrosis of human HaCaT keratinocytes, human Hs27 skin fibroblasts, human skin SCL II squamous cell carcinoma, and B16F10 melanoma cells were assessed in vitro, in correlation with the structural and photophysical properties of the investigated porphyrins, and with the predictions regarding diffusion through cell membranes and ADMET properties. All samples were found to be isotropic and self-similar, with slightly different degrees of aggregability, had a relatively low predicted toxicity (class V), and a predicted long half-life after systemic administration. The in vitro study performed on non-malignant and malignant skin-relevant cells highlighted that the asymmetric P2.2 porphyrin qualified among the five investigated porphyrins to be a promising photosensitizer candidate for PDT in skin disorders. P2.2 was shown to accumulate well within cells, and induced by PDT a massive decrease in the number of metabolically active skin cells, partly due to cell death by necrosis. P2.2 had in this respect a better behavior than the symmetric P.2.1 compound and the related asymmetric compound P4.2. The strong action of P2.2-mediated PDT on normal skin cells might be an important drawback for further development of this compound. Meanwhile, the P3.1 and P3.2 compounds were not able to accumulate well in skin cells, and did not elicit significant PDT in vitro. Taken together, our experiments suggest that P2.2 can be a promising candidate for the development of novel photosensitizers for PDT in skin disorders.
Funder
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania Ministry of Research and Innovation
Subject
Drug Discovery,Pharmaceutical Science,Molecular Medicine
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