Novel sulfonamide bearing coumarin scaffolds as selective inhibitors of tumor associated carbonic anhydrase isoforms IX and XII

Navneet Chandak; Mariangela Ceruso; Claudiu T Supuran; Pawan K Sharma

doi:10.1016/j.bmc.2016.04.052

Novel sulfonamide bearing coumarin scaffolds as selective inhibitors of tumor associated carbonic anhydrase isoforms IX and XII

Bioorg Med Chem. 2016 Jul 1;24(13):2882-2886. doi: 10.1016/j.bmc.2016.04.052. Epub 2016 Apr 26.

Authors

Navneet Chandak¹, Mariangela Ceruso², Claudiu T Supuran³, Pawan K Sharma⁴

Affiliations

¹ Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India.
² Università degli Studi di Fierenze, Laboratorio di Chimica Bioinorganica, Rm 188 and Neurofarba Department, Sezione di Scienze Farmaceutiche, Via U. Schiff 6, I-50019 Sesto Fiorentino (Firenze), Italy.
³ Università degli Studi di Fierenze, Laboratorio di Chimica Bioinorganica, Rm 188 and Neurofarba Department, Sezione di Scienze Farmaceutiche, Via U. Schiff 6, I-50019 Sesto Fiorentino (Firenze), Italy. Electronic address: claudiu.supuran@unifi.it.
⁴ Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India. Electronic address: pksharma@kuk.ac.in.

PMID: 27137360
DOI: 10.1016/j.bmc.2016.04.052

Abstract

Four novel scaffolds consisting of total 24 compounds (1a-1o, 2a-2c, 3a-3c and 4a-4c) bearing aromatic sulfonamide and coumarin moieties connected through various linkers were synthesized in order to synergize the inhibition potential of both the moieties against four selected human carbonic anhydrase isoforms (hCA I, II, IX & XII). All compounds were found to be potent inhibitors of tumor associated hCA IX & XII while at the same time required large amounts to inhibit off-targeted housekeeping hCA I & II. Selectivity was more pronounced against hCA II over I, and hCA XII over IX. Results were compared with antitumor drug acetazolamide. One derivative 2b of series 2 was found to be a better selective inhibitor of hCA IX and XII.

Keywords: Acetazolamide; Coumarin; Human carbonic anhydrase isoforms I, II, IX, XII; Sulfonamide; Synergistic inhibition.

Publication types

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

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Carbonic Anhydrase IX / antagonists & inhibitors*
Carbonic Anhydrase IX / chemistry
Carbonic Anhydrase IX / metabolism*
Carbonic Anhydrase Inhibitors / chemical synthesis*
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrases / chemistry
Carbonic Anhydrases / metabolism*
Coumarins / chemical synthesis
Coumarins / chemistry*
Enzyme Activation / drug effects
Humans
Isoenzymes / chemistry
Isoenzymes / metabolism
Molecular Structure
Sulfonamides / chemical synthesis*
Sulfonamides / chemistry
Sulfonamides / pharmacology

Substances

Antineoplastic Agents
Carbonic Anhydrase Inhibitors
Coumarins
Isoenzymes
Sulfonamides
Carbonic Anhydrase IX
Carbonic Anhydrases