Benzoxepinones: A new isoform-selective class of tumor associated carbonic anhydrase inhibitors

Aiga Grandane; Alessio Nocentini; Thomas Werner; Raivis Zalubovskis; Claudiu T Supuran

doi:10.1016/j.bmc.2020.115496

Benzoxepinones: A new isoform-selective class of tumor associated carbonic anhydrase inhibitors

Bioorg Med Chem. 2020 Jun 1;28(11):115496. doi: 10.1016/j.bmc.2020.115496. Epub 2020 Apr 14.

Authors

Aiga Grandane¹, Alessio Nocentini², Thomas Werner³, Raivis Zalubovskis⁴, Claudiu T Supuran⁵

Affiliations

¹ Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia. Electronic address: aiga@osi.lv.
² Università degli Studi di Firenze, NEUROFARBA Department, Section of Pharmaceutical Chemistry, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy.
³ Leibniz Institute for Catalysis, Albert-Einstein-Straße 29a, 18059 Rostock, Germany. Electronic address: thomas.werner@catalysis.de.
⁴ Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia; Institute of Technology of Organic Chemistry, Faculty of Materials Science and Applied Chemistry, Riga Technical University, 3/7 Paula Valdena Str., Riga LV-1048, Latvia.
⁵ Università degli Studi di Firenze, NEUROFARBA Department, Section of Pharmaceutical Chemistry, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy. Electronic address: claudiu.supuran@unifi.it.

PMID: 32327349
DOI: 10.1016/j.bmc.2020.115496

Abstract

Benzoxepinones ("homocoumarins") are identified as a new class of selective inhibitors for tumor associated human carbonic anhydrases (hCA, EC 4.2.1.1) isoforms IX and XII. Similar to coumarins, they do not inhibit or poorly inhibit cytosolic human (h) isoforms hCA I and II, but act as nanomolar inhibitors of the trans-membrane, tumor associated isoforms hCA IX and XII.

Keywords: Benzoxepinone; Carbonic anhydrase; Catalytic Wittig reaction; Selective inhibitor; Tumor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carbonic Anhydrase Inhibitors / chemical synthesis
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / pharmacology*
Carbonic Anhydrases / metabolism*
Coumarins / chemical synthesis
Coumarins / chemistry
Coumarins / pharmacology*
Dose-Response Relationship, Drug
Humans
Isoenzymes / antagonists & inhibitors
Isoenzymes / metabolism
Molecular Structure
Structure-Activity Relationship

Substances

Carbonic Anhydrase Inhibitors
Coumarins
Isoenzymes
Carbonic Anhydrases