Dual cyclooxygenase and carbonic anhydrase inhibition by nonsteroidal anti-inflammatory drugs for the treatment of cancer

Celeste De Monte, Simone Carradori, Andrea Gentili, Adriano Mollica, Daniela Trisciuoglio, Claudiu T. Supuran

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Among the class of nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors or "coxibs" selectively inhibit the activity of the inducible isoform of cyclooxygenase. Moreover, there is emerging evidence that the sulfonamide-type coxibs, but not the methylsulfones, display an inhibitory activity also against several isoforms of human carbonic anhydrase (CA, EC 4.2.1.1). In this regard, celecoxib and valdecoxib, possessing a primary sulfonamide that binds to the zinc ion at the active site of the enzyme, are nanomolar inhibitors of the cancer-related hCA IX isoform. Also meloxicam and lornoxicam, NSAIDs belonging to the class of "oxicams", that contain a cyclic tertiary sulfonamide moiety, inhibit this isoform at low micromolar concentrations. The multiple pharmacological effects of the sulfonamide anti-inflammatory agents could be ascribed to the dual inhibition of CA and COX enzymes, supporting the evidence that inflammation and hypoxia pathways are involved in cancer onset and progression and suggesting that the antitumoral activity of these compounds should be further explored for their possible use in the polypharmacology of cancer prevention and therapy.

Original languageEnglish
Pages (from-to)2812-2818
Number of pages7
JournalCurrent Medicinal Chemistry
Volume22
Issue number24
Publication statusPublished - Aug 1 2015

Fingerprint

Carbonic Anhydrases
Sulfonamides
Prostaglandin-Endoperoxide Synthases
Cyclooxygenase 2 Inhibitors
Protein Isoforms
Anti-Inflammatory Agents
meloxicam
Celecoxib
Pharmaceutical Preparations
Polypharmacology
Neoplasms
Enzyme Inhibitors
Zinc
Catalytic Domain
Pharmacology
Ions
Inflammation
Enzymes
Therapeutics

Keywords

  • Cancer
  • Carbonic anhydrase inhibitor
  • COX-2 inhibitor
  • Coxib
  • Oxicam

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Dual cyclooxygenase and carbonic anhydrase inhibition by nonsteroidal anti-inflammatory drugs for the treatment of cancer. / De Monte, Celeste; Carradori, Simone; Gentili, Andrea; Mollica, Adriano; Trisciuoglio, Daniela; Supuran, Claudiu T.

In: Current Medicinal Chemistry, Vol. 22, No. 24, 01.08.2015, p. 2812-2818.

Research output: Contribution to journalArticle

De Monte, Celeste ; Carradori, Simone ; Gentili, Andrea ; Mollica, Adriano ; Trisciuoglio, Daniela ; Supuran, Claudiu T. / Dual cyclooxygenase and carbonic anhydrase inhibition by nonsteroidal anti-inflammatory drugs for the treatment of cancer. In: Current Medicinal Chemistry. 2015 ; Vol. 22, No. 24. pp. 2812-2818.
@article{2bdea723f31c40618af1ed1552e8217e,
title = "Dual cyclooxygenase and carbonic anhydrase inhibition by nonsteroidal anti-inflammatory drugs for the treatment of cancer",
abstract = "Among the class of nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors or {"}coxibs{"} selectively inhibit the activity of the inducible isoform of cyclooxygenase. Moreover, there is emerging evidence that the sulfonamide-type coxibs, but not the methylsulfones, display an inhibitory activity also against several isoforms of human carbonic anhydrase (CA, EC 4.2.1.1). In this regard, celecoxib and valdecoxib, possessing a primary sulfonamide that binds to the zinc ion at the active site of the enzyme, are nanomolar inhibitors of the cancer-related hCA IX isoform. Also meloxicam and lornoxicam, NSAIDs belonging to the class of {"}oxicams{"}, that contain a cyclic tertiary sulfonamide moiety, inhibit this isoform at low micromolar concentrations. The multiple pharmacological effects of the sulfonamide anti-inflammatory agents could be ascribed to the dual inhibition of CA and COX enzymes, supporting the evidence that inflammation and hypoxia pathways are involved in cancer onset and progression and suggesting that the antitumoral activity of these compounds should be further explored for their possible use in the polypharmacology of cancer prevention and therapy.",
keywords = "Cancer, Carbonic anhydrase inhibitor, COX-2 inhibitor, Coxib, Oxicam",
author = "{De Monte}, Celeste and Simone Carradori and Andrea Gentili and Adriano Mollica and Daniela Trisciuoglio and Supuran, {Claudiu T.}",
year = "2015",
month = "8",
day = "1",
language = "English",
volume = "22",
pages = "2812--2818",
journal = "Current Medicinal Chemistry",
issn = "0929-8673",
publisher = "Bentham Science Publishers B.V.",
number = "24",

}

TY - JOUR

T1 - Dual cyclooxygenase and carbonic anhydrase inhibition by nonsteroidal anti-inflammatory drugs for the treatment of cancer

AU - De Monte, Celeste

AU - Carradori, Simone

AU - Gentili, Andrea

AU - Mollica, Adriano

AU - Trisciuoglio, Daniela

AU - Supuran, Claudiu T.

PY - 2015/8/1

Y1 - 2015/8/1

N2 - Among the class of nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors or "coxibs" selectively inhibit the activity of the inducible isoform of cyclooxygenase. Moreover, there is emerging evidence that the sulfonamide-type coxibs, but not the methylsulfones, display an inhibitory activity also against several isoforms of human carbonic anhydrase (CA, EC 4.2.1.1). In this regard, celecoxib and valdecoxib, possessing a primary sulfonamide that binds to the zinc ion at the active site of the enzyme, are nanomolar inhibitors of the cancer-related hCA IX isoform. Also meloxicam and lornoxicam, NSAIDs belonging to the class of "oxicams", that contain a cyclic tertiary sulfonamide moiety, inhibit this isoform at low micromolar concentrations. The multiple pharmacological effects of the sulfonamide anti-inflammatory agents could be ascribed to the dual inhibition of CA and COX enzymes, supporting the evidence that inflammation and hypoxia pathways are involved in cancer onset and progression and suggesting that the antitumoral activity of these compounds should be further explored for their possible use in the polypharmacology of cancer prevention and therapy.

AB - Among the class of nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors or "coxibs" selectively inhibit the activity of the inducible isoform of cyclooxygenase. Moreover, there is emerging evidence that the sulfonamide-type coxibs, but not the methylsulfones, display an inhibitory activity also against several isoforms of human carbonic anhydrase (CA, EC 4.2.1.1). In this regard, celecoxib and valdecoxib, possessing a primary sulfonamide that binds to the zinc ion at the active site of the enzyme, are nanomolar inhibitors of the cancer-related hCA IX isoform. Also meloxicam and lornoxicam, NSAIDs belonging to the class of "oxicams", that contain a cyclic tertiary sulfonamide moiety, inhibit this isoform at low micromolar concentrations. The multiple pharmacological effects of the sulfonamide anti-inflammatory agents could be ascribed to the dual inhibition of CA and COX enzymes, supporting the evidence that inflammation and hypoxia pathways are involved in cancer onset and progression and suggesting that the antitumoral activity of these compounds should be further explored for their possible use in the polypharmacology of cancer prevention and therapy.

KW - Cancer

KW - Carbonic anhydrase inhibitor

KW - COX-2 inhibitor

KW - Coxib

KW - Oxicam

UR - http://www.scopus.com/inward/record.url?scp=84940861057&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84940861057&partnerID=8YFLogxK

M3 - Article

VL - 22

SP - 2812

EP - 2818

JO - Current Medicinal Chemistry

JF - Current Medicinal Chemistry

SN - 0929-8673

IS - 24

ER -