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Design and synthesis of benzothiazole-6-sulfonamides acting as highly potent inhibitors of carbonic anhydrase isoforms I, II, IX and XII.
Bioorg Med Chem. 2015 Aug 01; 23(15):4989-4999.BM

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+Show Affiliations

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.Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, Egypt.National Organization for Drug Control and Research, Cairo, Egypt.National Organization for Drug Control and Research, Cairo, Egypt.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, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.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.Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26048024

Citation

Ibrahim, Diaa A., et al. "Design and Synthesis of Benzothiazole-6-sulfonamides Acting as Highly Potent Inhibitors of Carbonic Anhydrase Isoforms I, II, IX and XII." Bioorganic & Medicinal Chemistry, vol. 23, no. 15, 2015, pp. 4989-4999.
Ibrahim DA, Lasheen DS, Zaky MY, et al. Design and synthesis of benzothiazole-6-sulfonamides acting as highly potent inhibitors of carbonic anhydrase isoforms I, II, IX and XII. Bioorg Med Chem. 2015;23(15):4989-4999.
Ibrahim, D. A., Lasheen, D. S., Zaky, M. Y., Ibrahim, A. W., Vullo, D., Ceruso, M., Supuran, C. T., & Abou El Ella, D. A. (2015). Design and synthesis of benzothiazole-6-sulfonamides acting as highly potent inhibitors of carbonic anhydrase isoforms I, II, IX and XII. Bioorganic & Medicinal Chemistry, 23(15), 4989-4999. https://doi.org/10.1016/j.bmc.2015.05.019
Ibrahim DA, et al. Design and Synthesis of Benzothiazole-6-sulfonamides Acting as Highly Potent Inhibitors of Carbonic Anhydrase Isoforms I, II, IX and XII. Bioorg Med Chem. 2015 Aug 1;23(15):4989-4999. PubMed PMID: 26048024.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design and synthesis of benzothiazole-6-sulfonamides acting as highly potent inhibitors of carbonic anhydrase isoforms I, II, IX and XII. AU - Ibrahim,Diaa A, AU - Lasheen,Deena S, AU - Zaky,Maysoun Y, AU - Ibrahim,Amany W, AU - Vullo,Daniela, AU - Ceruso,Mariangela, AU - Supuran,Claudiu T, AU - Abou El Ella,Dalal A, Y1 - 2015/05/19/ PY - 2015/03/10/received PY - 2015/05/06/revised PY - 2015/05/09/accepted PY - 2015/6/7/entrez PY - 2015/6/7/pubmed PY - 2016/5/5/medline KW - Benzothiazole-6-sulfonamides KW - Carbonic anhydrase KW - Cytosolic isoforms I and II KW - Docking KW - Tumor-associated isoforms IX KW - XII SP - 4989 EP - 4999 JF - Bioorganic & medicinal chemistry JO - Bioorg. Med. Chem. VL - 23 IS - 15 N2 - 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. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/26048024/Design_and_synthesis_of_benzothiazole_6_sulfonamides_acting_as_highly_potent_inhibitors_of_carbonic_anhydrase_isoforms_I_II_IX_and_XII_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(15)00419-8 DB - PRIME DP - Unbound Medicine ER -