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Eur J Med Chem. 2014 Nov 24;87:186-96. doi: 10.1016/j.ejmech.2014.09.059. Epub 2014 Sep 19.

Novel sulfonamides bearing pyrrole and pyrrolopyrimidine moieties as carbonic anhydrase inhibitors: Synthesis, cytotoxic activity and molecular modeling.

Author information

1
Pharmacognosy Department, College of Pharmacy, King Saud University, P.O.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.
2
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Firenze, Italy.
3
Pharmacognosy Department, College of Pharmacy, King Saud University, P.O.Box 2457, Riyadh 11451, Saudi Arabia.
4
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr Al-Aini st., P.O.Box 11562, Cairo, Egypt.
5
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.

Abstract

Novel pyrrole and pyrrolopyrimidine scaffold-based sulfonamides were designed and synthesized. The carbonic anhydrase (CA) inhibition ability of all derivatives was assessed against the human (h) cytosolic isoforms hCA I and II and the transmembrane, tumor-associated isoforms hCA IX and XII. Some of these sulfonamides were 6-8 fold more potent than the reference drug acetazolamide (AZA, Ki = 5.7 nM)) against hCA XII showing subnanomolar activity. The in vitro cytotoxicity of these derivatives was evaluated against MCF-7, where some derivatives were more cytotoxic than doxorubicin (IC50 = 8.02 μM) displaying IC50 values between 6.46 and 7.56 μM. Docking of these sulfonamides with CA XII was performed and their binding modes were comparable with that of AZA.

KEYWORDS:

Carbonic anhydrase; Cytotoxic activity; Pyrroles; Pyrrolopyrimidines; Sulfonamides

PMID:
25255434
DOI:
10.1016/j.ejmech.2014.09.059
[Indexed for MEDLINE]

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