Interaction of Some Asymmetrical Porphyrins with U937 Cell Membranes–In Vitro and In Silico Studies

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.

In Silico and In Vitro Studies on an Asymmetrical Porphyrin Derivative with Therapeutic Potential in Skin Disorders

“…The unbound (apo) structure of CAIX was also simulated as a negative control structure, while the docked sulfonamide inhibitor was used as a positive control structure. Simulations were performed using YASARA Structure, for a total duration of 250 ns, similar to our previous studies [ 55 , 56 ]. The system stability was increased by optimizing the hydrogen bonding network.…”

Cytotoxicity Analysis and In Silico Studies of Three Plant Extracts with Potential Application in Treatment of Endothelial Dysfunction

“…Deionization energies were also considered for ionizable compounds. Results were retrieved as cell membrane binding affinity (ΔG, kcal/mol) and permeability coefficients (logPerm) and coordinates required for generating transfer energy profiles as a function of distance from the membrane center [ 13 ]. Ligands considered permeable through the plasma membrane were selected for further computational studies.…”

Porphyrin-Based Compounds: Synthesis and Application

“…Boscensu, Burloiu, Socoteanu and co-workers [21], investigated the effects exerted in vitro of three asymmetrical porphyrins, (5-(2-hydroxyphenyl)-10,15,20-tris(4-acetoxy-3methoxyphenyl)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 human U937 cell membranes. The porphyrins were studied for their impact on transmembrane potential and membrane anisotropy using fluorescent probes.…”