Thiosemicarbazide-Substituted Coumarins as Selective Inhibitors of the Tumor Associated Human Carbonic Anhydrases IX and XII

GÜMÜŞ PALABIYIK A., Bozdag M., AKDEMİR A., Angeli A., Selleri S., Carta F., ...More

MOLECULES, vol.27, no.14, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 27 Issue: 14
  • Publication Date: 2022
  • Doi Number: 10.3390/molecules27144610
  • Journal Name: MOLECULES
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Metadex, Veterinary Science Database, Directory of Open Access Journals, Civil Engineering Abstracts
  • Keywords: carbonic anhydrase inhibitors, privileged scaffolds, coumarins, thiosemicarbazides, THERMODYNAMICS, SOLVENT
  • Bezmialem Vakıf University Affiliated: Yes

Abstract

A novel series of thiosemicarbazide-substituted coumarins was synthesized and the inhibitory effects against four physiologically relevant carbonic anhydrase isoforms I, II, IX and XII showed selective activities on the tumor-associated IX and XII isozymes. Molecular modeling studies on selected compounds 14a and 22a were performed. The binding modes of such compounds were determined assuming their enzymatically active structures (i.e., cinnamic acid) in the thermodynamically favored, and not previously explored, E geometry. Molecular modelling suggests multiple interactions within the enzymatic cavity and may explain the high potency and selectivity reported for the hCAs IX and XII.