Inhibition of carbonic anhydrases from the extremophilic bacteria Sulfurihydrogenibium yellostonense (SspCA) and S. azorense (SazCA) with a new series of sulfonamides incorporating aroylhydrazone-, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenylmethylene)-1,3,4-thiadiazol-3(2H)-yl moieties

Ahmed M Alafeefy; Hatem A Abdel-Aziz; Daniela Vullo; Abdul-Malek S Al-Tamimi; Nabila A Al-Jaber; Clemente Capasso; Claudiu T Supuran

doi:10.1016/j.bmc.2013.11.042

Inhibition of carbonic anhydrases from the extremophilic bacteria Sulfurihydrogenibium yellostonense (SspCA) and S. azorense (SazCA) with a new series of sulfonamides incorporating aroylhydrazone-, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenylmethylene)-1,3,4-thiadiazol-3(2H)-yl moieties

Bioorg Med Chem. 2014 Jan 1;22(1):141-7. doi: 10.1016/j.bmc.2013.11.042. Epub 2013 Dec 1.

Authors

Ahmed M Alafeefy¹, Hatem A Abdel-Aziz², Daniela Vullo³, Abdul-Malek S Al-Tamimi⁴, Nabila A Al-Jaber⁵, Clemente Capasso⁶, Claudiu T Supuran⁷

Affiliations

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, Salman bin Abdulaziz University, PO Box 173, Alkharj 11942, Saudi Arabia. Electronic address: alafeefy@hotmail.com.
² Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia; Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo 12622, Egypt.
³ Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy.
⁴ Department of Pharmaceutical Chemistry, College of Pharmacy, Salman bin Abdulaziz University, PO Box 173, Alkharj 11942, Saudi Arabia.
⁵ Chemistry Department, Faculty of Science, King Saud University, Riyadh, Saudi Arabia.
⁶ Istituto di Biochimica delle Proteine-CNR, Via P. Castellino 111, 80131 Napoli, Italy.
⁷ Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy; Università degli Studi di Firenze, Neurofarba Dept., Section of Pharmaceutical and Nutriceutical Sciences, Via U. Schiff 6, 50019 Sesto Fiorentino (Florence), Italy. Electronic address: claudiu.supuran@unifi.it.

PMID: 24332658
DOI: 10.1016/j.bmc.2013.11.042

Abstract

A series of new sulfonamides was prepared starting from 2-oxo-N'-(4-sulfamoylphenyl)-propanehydrazonoyl chloride, a sulfanilamide derivative, which was reacted with aroylhydrazides, amines, or thiols. A library of derivatives incorporating aroylhydrazone, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenyl-methylene)-1,3,4-thiadiazol-3(2H)-yl moieties was thus synthesized. The new compounds were investigated as inhibitors of four α-carbonic anhydrases (CAs, EC 4.2.1.1), the human (h) isoforms hCA I and II, and the bacterial ones recently isolated from the extremophilic bacteria Sulfurihydrogenibium yellostonense (SspCA) and Sulfurihydrogenibium azorense (SazCA). Low nanomolar activity was observed against hCA II (KIs of 0.56-17.1 nM) whereas hCA I was less inhibited by these compounds (K(I)s of 86.4 nM-32.8 μM). The bacterial CAs were also effectively inhibited by these derivatives (K(I)s in the range of 0.77-234 nM against SazCA, and of 6.2-89.1 against SspCA, respectively), with several low nanomolar/subnanomolar inhibitors detected against both of them. As SspCA and SazCA are among the most thermostable and catalytically active CAs, it is of interest to find modulators of their activity for potential biotechnologic applications.

Keywords: Alpha-class enzyme; Carbonic anhydrase; Extremophiles; Inhibition study; Sulfonamide; Sulfurihydrogenibium spp..

Publication types

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

MeSH terms

Bacteria / metabolism
Carbonic Anhydrase Inhibitors / pharmacology*
Carbonic Anhydrases / metabolism*
Catalysis
Humans
Structure-Activity Relationship
Sulfonamides / pharmacology*

Substances

Carbonic Anhydrase Inhibitors
Sulfonamides
Carbonic Anhydrases