Синтез та оцінка нових тіазоловмісних роданін-3-алканових кислот як інгібіторів протеїнтирозинфосфатаз та глутатіон-S-трансфераз

• Main Authors: Kobzar, Oleksandr L., Sinenko, Vitaliy O., Shulha, Yuriy V., Buldenko, Vladyslav M., Hodyna, Diana M., Pilyo, Stepan G., Brovarets, Volodymyr S., 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 2020
• Subjects: rhodanine; thiazole; protein tyrosine phosphatase; glutathione S-transferase; enzyme inhibition; molecular docking; роданін; тіазол; протеїнтирозинфосфатаза; глутатіон-S-трансфераза; інгібування ферменту; молекулярний докінг
• Online Access: https://bioorganica.com.ua/index.php/journal/article/view/39

Thiazole-containing derivatives of rhodanine-3-alkanoic acids with propanoic or undecanoic acid groups were synthesized and evaluated as inhibitors of some protein tyrosine phosphatases and glutathione S-transferases. The rhodanines bearing longer carboxylated N-alkyl chain were found to inhibit PTP1B, MEG1, MEG2, and VE-PTP as well as GST from equine liver and GSTA1-1 with IC50 values in the low micromolar range. The inhibitory effect on protein tyrosine phosphatase activity depends on substituent at position 2 of the thiazole ring. The best compound showed a competitive type of VE-PTP inhibition. In case of GST from equine liver, the inhibition was of mixed or non-competitive type with respect to glutathione or CDNB substrate, respectively. Possible binding modes of the inhibitors were discussed based on molecular docking calculations