title: Carbonic anhydrase inhibitory properties of novel benzylsulfamides using molecular modeling and experimental studies.
abstract: In this study, a series of sulfamoyl carbamates and sulfamide derivatives were synthesized. Six commercially available benzyl amines and BnOH were reacted with chlorosulfonyl isocyanate (CSI) to give sulfamoyl carbamates. Pd-C catalyzed hydrogenolysis reactions of carbamates afforded sulfamides. The inhibition effects of novel benzylsulfamides on the carbonic anhydrase I, and II isoenzymes (CA I, and CA II) purified from fresh human blood red cells were determined by Sepharose-4B-L-Tyrosine-sulfanilamide affinity chromatography. In vitro studies were shown that all of novel synthesized benzylsulfamide analogs inhibited, concentration dependently, both hCA isoenzyme activities. The novel benzylsulfamide compounds investigated here exhibited nanomolar inhibition constants against the two isoenzymes. Ki values were in the range of 28.48±0.01-837.09±0.19nM and 112.01±0.01-268.01±0.22nM for hCAI and hCA II isoenzymes, respectively. Molecular modeling approaches were also applied for studied compounds.
authors.affiliation: Ataturk University, Faculty of Science, Department of Chemistry, Erzurum, Turkey. Electronic address: sgoksu@atauni.edu.tr.
authors.forename: Süleyman
authors.initials: S
authors.lastname: Göksu
authors.affiliation: Ataturk University, Faculty of Science, Department of Chemistry, Erzurum, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Naderi
authors.affiliation: Erzurum Technical University, Faculty of Science, Department of Basic Sciences, Erzurum, Turkey.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Akbaba
authors.affiliation: Ataturk University, Faculty of Science, Department of Chemistry, Erzurum, Turkey.
authors.forename: Pınar
authors.initials: P
authors.lastname: Kalın
authors.affiliation: Agri Ibrahim Cecen University, Central Researching Laboratory, 04200 Agri, Turkey.
authors.forename: Akın
authors.initials: A
authors.lastname: Akıncıoğlu
authors.affiliation: Ataturk University, Faculty of Science, Department of Chemistry, Erzurum, Turkey; Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: İlhami
authors.initials: İ
authors.lastname: Gülçin
authors.affiliation: Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul, Turkey.
authors.forename: Serdar
authors.initials: S
authors.lastname: Durdagi
authors.affiliation: Department of chemistry, Istanbul Technical University, Istanbul, Turkey.
authors.forename: Ramin Ekhteiari
authors.initials: RE
authors.lastname: Salmas
mesh_terms: D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II
keywords: Benzyl amine; Carbonic anhydrase; Enzyme inhibition; Molecular modeling; Sulfamide; Sulfamoyl carbamate