Benzenesulfonamides incorporating bulky aromatic/heterocyclic tails with potent carbonic anhydrase inhibitory activity

Bozdag M 1 , Alafeefy AM 2 , Vullo D 1 , Carta F 1 , Dedeoglu N 1 , Al-Tamimi AM 3 Show all authors , Al-Jaber NA 4 , Scozzafava A 1 , Supuran CT 5

Affiliations 

  • 1 Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy
  • 2 Chemistry Department, Kulliyyah of Science, International Islamic University, Kuantan, Malaysia
  • 3 Pharmaceutical Chemistry Dept., College of Pharmacy, Prince Sattam Bin Abdulaziz University, Saudi Arabia
  • 4 Chemistry Department, College of Science, King Saud University, Saudi Arabia
  • 5 Università degli Studi di Firenze, NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy. Electronic address: claudiu.supuran@unifi.it
Bioorg Med Chem, 2015 Dec 15;23(24):7751-64.
PMID: 26639945 DOI: 10.1016/j.bmc.2015.11.023

Abstract

Three series of sulfonamides incorporating long, bulky tails were obtained by applying synthetic strategies in which substituted anthranilic acids, quinazolines and aromatic sulfonamides have been used as starting materials. They incorporate long, bulky diamide-, 4-oxoquinazoline-3-yl- or quinazoline-4-yl moieties in their molecules, and were investigated for the inhibition of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic human (h) hCA I and II, as well as the transmembrane hCA IX and XII. Most of the new sulfonamides showed excellent inhibitory effects against the four isoforms, with KIs of 7.6-322nM against hCA I, of 0.06-85.4nM against hCA II; of 6.7-152nM against hCA IX and of 0.49-237nM against hCA XII; respectively. However no relevant isoform-selective behavior has been observed for any of them, although hCA II and XII, isoforms involved in glaucoma-genesis were the most inhibited ones. The structure-activity relationship for inhibiting the four CAs with these derivatives is discussed in detail.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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