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

Abstract

The scavenging effect of the antimetabolite dihydrofolate reductase inhibitor methotrexate (MTX) and the isomers of its photoswitchable derivate, cis- and trans-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 trans-phototrexate (trans-PHX). At a low concentration (100 µM) cis-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 trans-PHX and cis-PHX, but both of the isomers of PHX showed a higher antioxidant capacity than MTX. These findings imply that trans-PHX may have more pronounced anti-inflammatory and tissue-protective effects than MTX, despite the lack of its cytotoxic, antineoplastic effect.

Weak Interactions of the Isomers of Phototrexate and Two Cavitand Derivatives

“…To investigate the interaction of cis -PHX with the cavitand derivatives (TAC and TDC), the complete isomerization of the thermodynamically more stable trans -PHX has to be reached. To this purpose, UV light exposure (λ = 366 nm) was used, as in our previous work [ 23 ].…”

“…The mixture was equipped with a magnetic stirrer and stirred for one hour at room temperature. Subsequently, Tetrabromocavitand 1 [ 22 , 23 ] (964.3 mg, 1.0 mmol) was added to the reaction mixture, the flask was stirred at 80 °C for 18 h under argon atmosphere. The mixture was cooled to room temperature and poured into 250 mL of 2% hydrochloric acid.…”

Photoresponsive Small Molecule Inhibitors for the Remote Control of Enzyme Activity

“…More recently, Kunsági‐Máté and co‐workers have utilised 41 as a molecular tool to gain further insight into the antioxidant properties of the parent compound, methotrexate [45] . The reactive oxygen species (ROS) of both photoisomers of 41 and methotrexate were evaluated using ESR spectroscopy, in which the rate of ROS production was significantly slower in the presence of 41‐ E , compared to that of the photo‐enrich 41‐ Z or methotrexate .…”

Some Interactions of the Novel Photoswitchable Compound Phototrexate

“…ZSolt PReISZ 1,2 ; BaláZS BogNáR 1 ; taMáS KálaI 1,3 ; láSZló KolláR 3,4 ; SáNdoR KuNSágI-Máté 1,2,3…”