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Carbonic anhydrase inhibitors: Synthesis, molecular docking, cytotoxic and inhibition of the human carbonic anhydrase isoforms I, II, IX, XII with novel benzenesulfonamides incorporating pyrrole, pyrrolopyrimidine and fused pyrrolopyrimidine moieties.
Bioorg Med Chem. 2014 Jul 15; 22(14):3684-95.BM

Abstract

A series of novel pyrroles, pyrrolopyrimidines, pyrazolopyrrolopyrimidine, triazolopyrrolopyrimidines, tetrazolopyrrolopyrimidine, triazinopyrrolopyrimidines and pyrrolopyrimidotriazepines bearing the biologically active benzenesulfonamide moiety were synthesized by using pyrrole-o-amino-carbonitrile as key intermediate. All the synthesized compounds were evaluated for their in vitro carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects against the human (h) isoforms hCA I, II, IX and XII. Among the tested derivatives, compounds 16, 18 and 20-24 showed potent activity as inhibitors for the tumor associated transmembrane isoforms (hCA IX and XII) in the nanomolar and subnanomolar range, with high selectivity. All compounds underwent cytotoxic activity assays on human breast cancer cell line (MCF-7) showing effective activity, comparable to that of the clinically used drug doxorubicin.

Authors+Show Affiliations

Pharmacognosy Department, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia; Drug Radiation Research Department, National Center for Radiation Research & Technology, Atomic Energy Authority, Cairo, Egypt. Electronic address: mmsghorab@yahoo.com.Pharmacognosy Department, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr Al-Aini st., PO Box 11562, 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, 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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24878360

Citation

Ghorab, Mostafa M., et al. "Carbonic Anhydrase Inhibitors: Synthesis, Molecular Docking, Cytotoxic and Inhibition of the Human Carbonic Anhydrase Isoforms I, II, IX, XII With Novel Benzenesulfonamides Incorporating Pyrrole, Pyrrolopyrimidine and Fused Pyrrolopyrimidine Moieties." Bioorganic & Medicinal Chemistry, vol. 22, no. 14, 2014, pp. 3684-95.
Ghorab MM, Alsaid MS, Ceruso M, et al. Carbonic anhydrase inhibitors: Synthesis, molecular docking, cytotoxic and inhibition of the human carbonic anhydrase isoforms I, II, IX, XII with novel benzenesulfonamides incorporating pyrrole, pyrrolopyrimidine and fused pyrrolopyrimidine moieties. Bioorg Med Chem. 2014;22(14):3684-95.
Ghorab, M. M., Alsaid, M. S., Ceruso, M., Nissan, Y. M., & Supuran, C. T. (2014). Carbonic anhydrase inhibitors: Synthesis, molecular docking, cytotoxic and inhibition of the human carbonic anhydrase isoforms I, II, IX, XII with novel benzenesulfonamides incorporating pyrrole, pyrrolopyrimidine and fused pyrrolopyrimidine moieties. Bioorganic & Medicinal Chemistry, 22(14), 3684-95. https://doi.org/10.1016/j.bmc.2014.05.009
Ghorab MM, et al. Carbonic Anhydrase Inhibitors: Synthesis, Molecular Docking, Cytotoxic and Inhibition of the Human Carbonic Anhydrase Isoforms I, II, IX, XII With Novel Benzenesulfonamides Incorporating Pyrrole, Pyrrolopyrimidine and Fused Pyrrolopyrimidine Moieties. Bioorg Med Chem. 2014 Jul 15;22(14):3684-95. PubMed PMID: 24878360.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Carbonic anhydrase inhibitors: Synthesis, molecular docking, cytotoxic and inhibition of the human carbonic anhydrase isoforms I, II, IX, XII with novel benzenesulfonamides incorporating pyrrole, pyrrolopyrimidine and fused pyrrolopyrimidine moieties. AU - Ghorab,Mostafa M, AU - Alsaid,Mansour S, AU - Ceruso,Mariangela, AU - Nissan,Yassin M, AU - Supuran,Claudiu T, Y1 - 2014/05/14/ PY - 2014/03/27/received PY - 2014/05/05/revised PY - 2014/05/06/accepted PY - 2014/6/1/entrez PY - 2014/6/1/pubmed PY - 2014/12/30/medline KW - Carbonic anhydrase inhibitors KW - Cytotoxic activity KW - Molecular docking KW - Pyrrolopyrimidines KW - Sulfonamide SP - 3684 EP - 95 JF - Bioorganic & medicinal chemistry JO - Bioorg. Med. Chem. VL - 22 IS - 14 N2 - A series of novel pyrroles, pyrrolopyrimidines, pyrazolopyrrolopyrimidine, triazolopyrrolopyrimidines, tetrazolopyrrolopyrimidine, triazinopyrrolopyrimidines and pyrrolopyrimidotriazepines bearing the biologically active benzenesulfonamide moiety were synthesized by using pyrrole-o-amino-carbonitrile as key intermediate. All the synthesized compounds were evaluated for their in vitro carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects against the human (h) isoforms hCA I, II, IX and XII. Among the tested derivatives, compounds 16, 18 and 20-24 showed potent activity as inhibitors for the tumor associated transmembrane isoforms (hCA IX and XII) in the nanomolar and subnanomolar range, with high selectivity. All compounds underwent cytotoxic activity assays on human breast cancer cell line (MCF-7) showing effective activity, comparable to that of the clinically used drug doxorubicin. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/24878360/Carbonic_anhydrase_inhibitors:_Synthesis_molecular_docking_cytotoxic_and_inhibition_of_the_human_carbonic_anhydrase_isoforms_I_II_IX_XII_with_novel_benzenesulfonamides_incorporating_pyrrole_pyrrolopyrimidine_and_fused_pyrrolopyrimidine_moieties_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(14)00349-6 DB - PRIME DP - Unbound Medicine ER -