Інгібування глутатіон S-трансфераз A1-1 та P1-1 піразолоновмісними 4-(5-заміщеними фуран-2-іл)бензойними кислотами, приєднаними до піразолону

• Date: 2025
• Main Authors: Shulha, Yurii V., Kobzar, Oleksandr L., Pilyo, Stepan G., Vovk, Andriy I.
• Format: Article
• Language: English
• Published: V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2025
• Subjects: 4-(фуран-2-іл)бензойні кислоти; піразолони; глутатіон S-трансферази; інгібування
• Online Access: https://bioorganica.com.ua/index.php/journal/article/view/122
• Journal Title: Ukrainica Bioorganica Acta

4-(5-Substituted furan-2-yl)benzoic acids with a pyrazolone moiety were evaluated in vitro as inhibitors of human cytosolic glutathione S-transferases A1-1 and P1-1, which are involved in cellular mechanisms of drug resistance and carcinogenesis. When inhibiting GSTA1-1, the compounds demonstrated micromolar and nanomolar IC50 values depending on the nature of the substituent at position 3 of the pyrazolone ring. In particular, the inhibition was increased when the methyl group was replaced by a trifluoromethyl, phenyl, 4-fluorophenyl, thiophen-2-yl, or pyridin-4-yl substituent. The effect of the 4-(5-substituted furan-2-yl)benzoic acids on GSTP1-1 was approximately an order of magnitude lower than that on GSTA1-1. In both cases, the compound bearing a 1-phenyl-3-(4-nitrophenyl)-substituted pyrazolone moiety demonstrated the best inhibitory activity among the derivatives studied. Molecular docking results indicated that the inhibitors interact with GSTA1-1 mainly due to the participation of amino acid residues from the G-site, while in the case of GSTP1-1 the compounds bind to the H-site