Synthesis and biological evaluation of cyclic imides incorporating benzenesulfonamide moieties as carbonic anhydrase I, II, IV and IX inhibitors.
A group of cyclic imides was synthesized by reaction of amino-substituted benzenesulfonamides with a series of acid anhydrides such as succinic, maleic, tetrahydrophthalic, pyrazine-2,3-dicarboxylic acid anhydride, and substituted phthalic anhydrides. The synthesized sulfonamides were evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors against the human (h) isoforms hCA I, II, IV and IX, involved in a variety of diseases among which glaucoma, retinitis pigmentosa, etc. Some of these sulfonamides showed effective inhibitory action (in the nanomolar range) against the cytosolic isoform hCA II and the transmembrane, tumor-associated one hCA IX, making them interesting candidates for preclinical evaluation in glaucoma or various tumors in which the two enzymes are involved. hCA I and IV were on the other hand less inhibited by these sulfonamides, with inhibition constants in the micromolar range.
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt; Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: alaa_moenes@yahoo.com.
Alaa A-M
AA
Abdel-Aziz
Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
Andrea
A
Angeli
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt.
Adel S
AS
El-Azab
Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
Mohamed A
MA
Abu El-Enin
Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: claudiu.supuran@unifi.it.
Claudiu T
CT
Supuran
D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007094:Imides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D066244:Proton Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry*; D000096926:Benzenesulfonamides
D002257:Carbonic Anhydrase Inhibitors; D007094:Imides; D013449:Sulfonamides; D000096926:Benzenesulfonamides
Benzenesulfonamide; Carbonic anhydrase; Cyclic imide; Inhibitor