Interaction of Some Asymmetrical Porphyrins with U937 Cell Membranes–In Vitro and In Silico Studies
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Published:2023-02-08
Issue:4
Volume:28
Page:1640
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ISSN:1420-3049
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Container-title:Molecules
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language:en
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Short-container-title:Molecules
Author:
Mihai Dragos Paul1ORCID, Boscencu Rica1, Manda Gina2ORCID, Burloiu Andreea Mihaela1, Vasiliu Georgiana1, Neagoe Ionela Victoria2, Socoteanu Radu Petre3, Lupuliasa Dumitru1
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, 99-101 Splaiul Independentei, 050096 Bucharest, Romania 3. “Ilie Murgulescu” Institute of Physical Chemistry, Romanian Academy, 202 Splaiul Independentei, 060021 Bucharest, Romania
Abstract
The aim of the present study was to assess the effects exerted in vitro by three asymmetrical porphyrins (5-(2-hydroxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin, 5-(2-hydroxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrinatozinc(II), and 5-(2-hydroxyphenyl)-10,15,20–tris-(4-acetoxy-3-methoxyphenyl)porphyrinatocopper(II)) on the transmembrane potential and the membrane anisotropy of U937 cell lines, using bis-(1,3-dibutylbarbituric acid)trimethine oxonol (DiBAC4(3)) and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene p-toluenesulfonate (TMA-DPH), respectively, as fluorescent probes for fluorescence spectrophotometry. The results indicate the hyperpolarizing effect of porphyrins in the concentration range of 0.5, 5, and 50 μM on the membrane of human U937 monocytic cells. Moreover, the tested porphyrins were shown to increase membrane anisotropy. Altogether, the results evidence the interaction of asymmetrical porphyrins with the membrane of U937 cells, with potential consequences on cellular homeostasis. Molecular docking simulations, and Molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) free energy of binding calculations, supported the hypothesis that the investigated porphyrinic compounds could potentially bind to membrane proteins, with a critical role in regulating the transmembrane potential. Thus, both the free base porphyrins and the metalloporphyrins could bind to the SERCA2b (sarco/endoplasmic reticulum ATPase isoform 2b) calcium pump, while the metal complexes may specifically interact and modulate calcium-dependent (large conductance calcium-activated potassium channel, Slo1/KCa1.1), and ATP-sensitive (KATP), potassium channels. Further studies are required to investigate these interactions and their impact on cellular homeostasis and functionality.
Funder
“Carol Davila” University of Medicine and Pharmacy
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
Reference58 articles.
1. Socoteanu, R., Boscencu, R., Hirtopeanu, A., Manda, G., Sousa, A., Ilie, M., and Vieira Ferreir, L.F. (2011). Biomedical Engineering—From Theory to Applications, InTech. 2. An updated overview on the development of new photosensitizers for anticancer photodynamic therapy;Zhang;Acta Pharm. Sin. B,2018 3. Cancer nanotheranostics: Strategies, promises and impediments;Schumann;Biomed. Pharmacother.,2016 4. The role of porphyrin chemistry in tumor imaging and photodynamic therapy;Ethirajan;Chem. Soc. Rev.,2011 5. Unique Diagnostic and Therapeutic Roles of Porphyrins and Phthalocyanines in Photodynamic Therapy, Imaging and Theranostics;Josefsen;Theranostics,2012
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