title: Design and synthesis of benzothiazole-6-sulfonamides acting as highly potent inhibitors of carbonic anhydrase isoforms I, II, IX and XII.
abstract: A series of novel 2-aminobenzothiazole derivatives bearing sulfonamide at position 6 was designed, synthesized and investigated as inhibitors of four isoforms of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), the cytosolic CA I and II, and the tumor-associated isozymes CA IX and XII. Docking and binding energy studies were carried out to reveal details regarding the favorable interactions between the scaffolds of these new inhibitors and the active sites of the investigated CA isoforms. Most of the novel compounds were acting as highly potent inhibitors of the tumor-associated hCA IX and hCA XII with KIs in the nanomolar range. The ubiquitous and dominant rapid cytosolic isozyme hCA II was also inhibited with KIs ranging from 3.5 to 45.4 nM. The favorable interactions between some of the new compounds and the active site of different CA isoforms were delineated by using molecular docking which may be useful for designing compounds with high affinity and selectivity for some CAs with biomedical applications.
authors.affiliation: Organic Chemistry Department, Faculty of Science, Jazan University, Jazan, Saudi Arabia; National Organization for Drug Control and Research, Cairo, Egypt. Electronic address: diaarnm@gmail.com.
authors.forename: Diaa A
authors.initials: DA
authors.lastname: Ibrahim
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, Egypt.
authors.forename: Deena S
authors.initials: DS
authors.lastname: Lasheen
authors.affiliation: National Organization for Drug Control and Research, Cairo, Egypt.
authors.forename: Maysoun Y
authors.initials: MY
authors.lastname: Zaky
authors.affiliation: National Organization for Drug Control and Research, Cairo, Egypt.
authors.forename: Amany W
authors.initials: AW
authors.lastname: Ibrahim
authors.affiliation: Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.affiliation: Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Ceruso
authors.affiliation: Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy; Università degli Studi di Firenze, Polo Scientifico, Dipartimento NEUROFABA, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Firenze), Italy. Electronic address: claudiu.supuran@unifi.it.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, Egypt.
authors.forename: Dalal A
authors.initials: DA
authors.lastname: Abou El Ella
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry / Q000378:metabolism; D052160:Benzothiazoles / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D024401:Carbonic Anhydrase I / Q000737:chemistry / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000737:chemistry / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D052160:Benzothiazoles; D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; C477378:carbonic anhydrase XII; C005465:benzothiazole
keywords: Benzothiazole-6-sulfonamides; Carbonic anhydrase; Cytosolic isoforms I and II; Docking; Tumor-associated isoforms IX; XII