• Aleksandrs Pustenko
  • Alessio Nocentini
  • Anastasija Balašova
  • Mikhail Krasavin
  • Raivis Žalubovskis
  • Claudiu T. Supuran

A series of 3H-1,2-benzoxathiepine 2,2-dioxides incorporating 7-acylamino moieties were obtained by an original procedure starting from 5-nitrosalicylaldehyde, which was treated with propenylsulfonyl chloride followed by Wittig reaction of the bis-olefin intermediate. The new derivatives, belonging to the homosulfocoumarin chemotype, were assayed as inhibitors of the zinc metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Four pharmacologically relevant human (h) isoforms were investigated, the cytosolic hCA I and II and the transmembrane, tumour-associated hCA IX and XII. No relevant inhibition of hCA I and II was observed, whereas some of the new derivatives were effective, low nanomolar hCA IX/XII inhibitors, making them of interest for investigations in situations in which the activity of these isoforms is overexpressed, such as hypoxic tumours, arthritis or cerebral ischaemia.

Original languageEnglish
Pages (from-to)650-656
Number of pages7
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume35
Issue number1
Early online date21 Feb 2020
DOIs
StatePublished - 1 Dec 2020

    Research areas

  • Carbonic anhydrase, homosulfocoumarin, isoform-selective inhibitor, sulfocoumarin, transmembrane isoforms, TRANSMEMBRANE, SULFONAMIDES, ALPHA, ISOZYMES I, BACTERIAL, COUMARINS, DISCOVERY, POTENT, SULFOCOUMARINS, DERIVATIVES

    Scopus subject areas

  • Drug Discovery
  • Pharmacology

ID: 52203682