Novel thiazolidinone-containing compounds, without the well-known sulphonamide zinc-binding group acting as human carbonic anhydrase IX inhibitors

Guzel-Akdemir O., Angeli A., Demir K., Supuran C. T., AKDEMİR A.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, cilt.33, sa.1, ss.1299-1308, 2018 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 33 Sayı: 1
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1080/14756366.2018.1499628
  • Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1299-1308
  • Anahtar Kelimeler: carbonic anhydrase IX, hCA IX, thiazolidinone, molecular modelling, docking, TARGETING TUMOR HYPOXIA, BIOLOGICAL EVALUATION, SELECTIVE INHIBITORS, DERIVATIVES, POTENT, XII, AGENTS, 4-THIAZOLIDINONE, ANTIFUNGAL, ISOZYMES
  • İstanbul Üniversitesi Adresli: Evet

Özet

A small collection of 26 structurally novel thiazolidinone-containing compounds, without the well-known sulphonamide zinc-binding group, were synthesised and tested in enzyme inhibition assays against the tumour-associated hCA IX enzyme. Inhibition constants in the lower micromolar region (K-I <25 mu M) have been measured for 17 of the 26 compounds. Even though the K-I values are relatively weak, the fact that they do not contain a sulphonamide moiety suggests that these compounds do not interact with the active site zinc ion. Therefore, docking studies and molecular dynamics simulations have been performed to suggest binding poses for these structurally novel inhibitors.