DOI

A hypothesis that simultaneous targeting cancer-related carbonic anhydrase hCA IX and hCA XII isoforms (whose overexpression is a cancer cell’s defence mechanism against hypoxia) along with thioredoxin reductase (overexpressed in cancers as a defence against oxidative stress) may lead to synergistic antiproliferative effects was confirmed by testing combinations of the two inhibitor classes against pancreatic cancer cells (PANC-1). Combining both pharmacophoric motifs within one molecule led to a sharp increase of cytotoxicity. This preliminary observation sets the ground for a fundamentally new approach to anticancer agent design.

Original languageEnglish
Pages (from-to)665-671
Number of pages7
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume35
Issue number1
Early online date5 Mar 2020
DOIs
StatePublished - 2020

    Scopus subject areas

  • Drug Discovery
  • Pharmacology

    Research areas

  • Anticancer agents, cancer cell defence mechanisms, carbonic anhydrase inhibition, dual pharmacophores, hypoxia, Michael acceptors, oxidative stress, synergistic effect, thioredoxin reductase inhibition, zinc-binding group, Humans, Structure-Activity Relationship, Cell Survival/drug effects, Thioredoxin-Disulfide Reductase/antagonists & inhibitors, Antineoplastic Agents/chemical synthesis, Dose-Response Relationship, Drug, Cell Line, Tumor, Carbonic Anhydrases/metabolism, Molecular Structure, Sulfonamides/chemical synthesis, Cell Proliferation/drug effects, Enzyme Inhibitors/chemical synthesis, Drug Screening Assays, Antitumor, SYSTEM, DESIGN, PERIPHERY

ID: 52376043