Comparative EPR Study on the Scavenging Effect of Methotrexate with the Isomers of Its Photoswitchable Derivative

• Main Authors: Zsolt Preisz, Nóra Hartvig, Balázs Bognár, Tamás Kálai, Sándor Kunsági-Máté
• Format: Article
• Language: English
• Published: MDPI AG 2021-07-01
• Series: Pharmaceuticals
• Subjects: methotrexate; phototrexate; photopharmacology; photoswitchable; electron paramagnetic resonance (EPR); scavenger
• Online Access: https://www.mdpi.com/1424-8247/14/7/665

The scavenging effect of the antimetabolite dihydrofolate reductase inhibitor methotrexate (MTX) and the isomers of its photoswitchable derivate, <i>cis</i>- and <i>trans</i>-phototrexate (PHX), have been compared by ESR spectroscopy, with the application of a cyclic hydroxylamine spin probe. The results showed the most pronounced scavenging effect in the presence of <i>trans</i>-phototrexate (<i>trans</i>-PHX). At a low concentration (100 µM) <i>cis</i>-PHX also showed a greater scavenging effect than the parent molecule MTX. Direct antioxidant properties of the investigated molecules were measured by ABTS scavenging assay, which showed no significant difference between <i>trans</i>-PHX and <i>cis</i>-PHX, but both of the isomers of PHX showed a higher antioxidant capacity than MTX. These findings imply that <i>trans</i>-PHX may have more pronounced anti-inflammatory and tissue-protective effects than MTX, despite the lack of its cytotoxic, antineoplastic effect.