Novel indolin-2-one-based sulfonamides as carbonic anhydrase inhibitors: Synthesis, in vitro biological evaluation against carbonic anhydrases isoforms I, II, IV and VII and molecular docking studies

Wagdy M Eldehna; Ghada H Al-Ansary; Silvia Bua; Alessio Nocentini; Paola Gratteri; Ayman Altoukhy; Hazem Ghabbour; Hanaa Y Ahmed; Claudiu T Supuran

doi:10.1016/j.ejmech.2017.01.017

Novel indolin-2-one-based sulfonamides as carbonic anhydrase inhibitors: Synthesis, in vitro biological evaluation against carbonic anhydrases isoforms I, II, IV and VII and molecular docking studies

Eur J Med Chem. 2017 Feb 15:127:521-530. doi: 10.1016/j.ejmech.2017.01.017. Epub 2017 Jan 11.

Authors

Wagdy M Eldehna¹, Ghada H Al-Ansary², Silvia Bua³, Alessio Nocentini⁴, Paola Gratteri⁵, Ayman Altoukhy⁶, Hazem Ghabbour⁷, Hanaa Y Ahmed⁸, Claudiu T Supuran⁹

Affiliations

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt. Electronic address: wagdy2000@gmail.com.
² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Abbassia, P.O. Box 11566, Egypt.
³ Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino (Firenze), Italy.
⁴ Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino (Firenze), Italy; Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino (Firenze), Italy.
⁵ Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino (Firenze), Italy.
⁶ Industrial Biotechnology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), Sadat City University, Egypt.
⁷ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia; Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
⁸ The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, Egypt.
⁹ Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino (Firenze), Italy. Electronic address: claudiu.supuran@unifi.it.

PMID: 28109946
DOI: 10.1016/j.ejmech.2017.01.017

Abstract

Herein we present the design, synthesis, and biological evaluation of three different series of novel sulfonamides (3a-f, 6a-f and 9a-f) incorporating substituted indolin-2-one moieties (as tails) linked to benzenesulfonamide (as zinc anchoring moieties) through aminoethyl or (4-oxothiazolidin-2-ylidene)aminoethyl linkers. The synthesized sulfonamides were evaluated in vitro for their inhibitory activity against the following human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IV and VII. All these isoforms were inhibited by the sulfonamides reported here in variable degrees. hCA I was inhibited with K_Is in the range of 42-8550.9 nM, hCA II in the range of 5.9-761 nM; hCA IV in the range of 4.0-2069.5 nM, whereas hCA VII in the range of 13.2-694 nM. Molecular docking studies were carried out for some of the tested compounds within the hCA II active site, allowed us to rationalize the obtained inhibition results.

Keywords: 4-(2-Aminoethyl)benzenesulfonamide; Carbonic anhydrase; Isatin; Synthesis.

MeSH terms

Carbonic Anhydrase I / antagonists & inhibitors
Carbonic Anhydrase II / antagonists & inhibitors
Carbonic Anhydrase IV / antagonists & inhibitors
Carbonic Anhydrase Inhibitors / chemical synthesis*
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / metabolism
Carbonic Anhydrase Inhibitors / pharmacology*
Carbonic Anhydrases / chemistry
Carbonic Anhydrases / metabolism*
Catalytic Domain
Chemistry Techniques, Synthetic
Drug Design
Humans
Indoles / chemistry*
Isoenzymes / antagonists & inhibitors
Isoenzymes / chemistry
Isoenzymes / metabolism
Molecular Docking Simulation*
Structure-Activity Relationship
Sulfonamides / chemical synthesis*
Sulfonamides / chemistry
Sulfonamides / metabolism
Sulfonamides / pharmacology*

Substances

Carbonic Anhydrase Inhibitors
Indoles
Isoenzymes
Sulfonamides
indolin-2-one
Carbonic Anhydrase I
Carbonic Anhydrase II
Carbonic Anhydrase IV
Carbonic Anhydrases
carbonic anhydrase VI