Synthesis and human/bacterial carbonic anhydrase inhibition with a series of sulfonamides incorporating phthalimido moieties

Menshawy A Mohamed; Alaa A-M Abdel-Aziz; Helmy M Sakr; Adel S El-Azab; Silvia Bua; Claudiu T Supuran

doi:10.1016/j.bmc.2017.03.017

Synthesis and human/bacterial carbonic anhydrase inhibition with a series of sulfonamides incorporating phthalimido moieties

Bioorg Med Chem. 2017 Apr 15;25(8):2524-2529. doi: 10.1016/j.bmc.2017.03.017. Epub 2017 Mar 9.

Authors

Menshawy A Mohamed¹, Alaa A-M Abdel-Aziz², Helmy M Sakr³, Adel S El-Azab⁴, Silvia Bua⁵, Claudiu T Supuran⁶

Affiliations

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj, Saudi Arabia; Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
² Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
⁴ Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. Electronic address: adelazaba@yahoo.com.
⁵ NEUROFARBA Department, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Via U. Schiff 6, 50019 Sesto, Fiorentino, Firenze, Italy.
⁶ NEUROFARBA Department, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Via U. Schiff 6, 50019 Sesto, Fiorentino, Firenze, Italy. Electronic address: claudiu.supuran@unifi.it.

PMID: 28318894
DOI: 10.1016/j.bmc.2017.03.017

Abstract

A series of sulfonamides was obtained by reacting substituted-2-(1,3-dioxo-1,3-dihydroisobenzofuran-5-carboxamido)benzoic acids with aromatic sulfonamides incorporating primary amino moieties. The new compounds were investigated as inhibitor of four carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the human (h) hCA I and II, and the α- and β-class CAs from the pathogenic bacterium Vibrio cholerae, VchCAα and VhcCAβ. hCA I was effectively inhibited by the new sulfonamides, with inhibition constants in the range of 4.9-96.0nM. hCA II also showed high affinity for these compounds (K_Is of 2.1-22.3nM), whereas the two bacterial enzymes were less effectively inhibited, with K_Is of 281-3192nM for VchCAα, and 5.40-9.26µM for VhcCAβ. As the physiological function hCA I is poorly understood, and it was recently shown to be involved in the pathogenesis of cerebral malaria and amyotrophic lateral sclerosis, selective and effective inhibitors may be useful as tools or drugs for better understanding this abundant isoform.

Keywords: Carbonic anhydrase; Phthalimide; Sulfonamide; Vibrio cholerae; β-Class enzyme.

MeSH terms

Carbonic Anhydrase Inhibitors / chemical synthesis*
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / pharmacology*
Humans
Phthalimides / chemistry*
Sulfonamides / chemistry
Sulfonamides / pharmacology*
Vibrio cholerae / enzymology*

Substances

Carbonic Anhydrase Inhibitors
Phthalimides
Sulfonamides