Chalcogenides-incorporating carbonic anhydrase inhibitors concomitantly reverted oxaliplatin-induced neuropathy and enhanced antiproliferative action

Damiano Tanini; Simone Carradori; Antonella Capperucci; Lucrezia Lupori; Susi Zara; Marta Ferraroni; Carla Ghelardini; Ldc Mannelli; Laura Micheli; Elena Lucarini; Fabrizio Carta; Andrea Angeli; Claudiu T Supuran

doi:10.1016/j.ejmech.2021.113793

Chalcogenides-incorporating carbonic anhydrase inhibitors concomitantly reverted oxaliplatin-induced neuropathy and enhanced antiproliferative action

Eur J Med Chem. 2021 Dec 5:225:113793. doi: 10.1016/j.ejmech.2021.113793. Epub 2021 Aug 23.

Affiliations

¹ University of Florence, Department of Chemistry "Ugo Schiff", Via Della Lastruccia 3-13, I-50019, Sesto Fiorentino, Italy.
² Department of Pharmacy, "G. D'Annunzio" University of Chieti-Pescara, Chieti, Italy.
³ Pharmacology and Toxicology Section, Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Firenze, Firenze, Italy.
⁴ NEUROFARBA Department, Sezione di Scienze Farmaceutiche, University of Florence, Via Ugo Schiff 6, 50019, Sesto Fiorentino, Florence, Italy.
⁵ NEUROFARBA Department, Sezione di Scienze Farmaceutiche, University of Florence, Via Ugo Schiff 6, 50019, Sesto Fiorentino, Florence, Italy; Centre of Advanced Research in Bionanoconjugates and Biopolymers Department, "Petru Poni" Institute of Macromolecular Chemistry, 707410, Iasi, Romania. Electronic address: andrea.angeli@unifi.it.

PMID: 34507012
DOI: 10.1016/j.ejmech.2021.113793

Abstract

Platinum-based chemotherapy is widely used for the treatment of different tumors but is associated with serious side effects, among which neuropathic pain. Carbonic anhydrase (CA, EC 4.2.1.1) inhibitors have recently been validated as therapeutic agents in neuropathic pain and as antitumor agents. We report the synthesis of new organochalcogenides bearing the benzensulfonamide moiety acting as potent inhibitors of several human CA isoforms and, in particular, against hCA II and VII endowed with potent neuropathic pain attenuating effects. Moreover, in combination with cisplatin or doxorubicin, some of the new CA inhibitors enhanced the effects of the anticancer drugs capability in counteracting breast cancer MCF7 cell viability. The concomitant anti-neuropathic pain and antiproliferative effects of the new chalcogenide-based CA inhibitors represent an innovative approach for the counteraction and management of side effects associated with clinically platinum drugs as antitumor agents.

Keywords: Antiproliferative effect; Carbonic anhydrase; Inhibitor; Metalloenzymes; Neuropathic pain; Organochalcogenide.

MeSH terms

Administration, Oral
Animals
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Carbonic Anhydrase Inhibitors / administration & dosage
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / pharmacology*
Carbonic Anhydrases / metabolism*
Cell Proliferation / drug effects
Chalcogens / chemical synthesis
Chalcogens / chemistry
Chalcogens / pharmacology*
Cisplatin / administration & dosage
Cisplatin / chemistry
Cisplatin / pharmacology*
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Isoenzymes / antagonists & inhibitors
Isoenzymes / metabolism
MCF-7 Cells
Male
Mice
Molecular Structure
Neuralgia / chemically induced
Neuralgia / drug therapy*
Oxaliplatin
Oxidative Stress / drug effects
Pain Measurement
Structure-Activity Relationship

Substances

Antineoplastic Agents
Carbonic Anhydrase Inhibitors
Chalcogens
Isoenzymes
Oxaliplatin
Carbonic Anhydrases
Cisplatin