Pyrazolo[4,3-e][1,2,4]triazine sulfonamides as carbonic anhydrase inhibitors with antitumor activity
- Bioorg Med Chem. 2014 May 1;22(9):2643-7. doi: 10.1016/j.bmc.2014.03.029.
Affiliations
- 1. Department of Chemistry, Siedlce University of Natural Sciences and Humanities, 3-go Maja 54, 08-110 Siedlce, Poland. Electronic address: [email protected].
- 2. Department of Medicinal Chemistry and Drug Technology, Medical University of Bialystok, Bialystok, Poland.
- 3. Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
- 4. Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy; Università degli Studi di Firenze, NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: [email protected].
PMID: 24713308
DOI: 10.1016/j.bmc.2014.03.029
Abstract
A series of sildenafil analogues and aniline substituted pyrazolo[4,3-e][1,2,4]triazine sulfonamides were prepared and evaluated as Carbonic Anhydrase (CA, EC 4.2.1.1) inhibitors and for their Anticancer activity against two human breast Cancer cell lines (MCF-7, MDA-MB-231). The new compounds were ineffective as CA I inhibitors, poorly inhibited CA II, but were more effective against the tumor-associated isoforms CA IX and XII, with some compounds acting as low nanomolar inhibitors. Evaluation of the cytotoxicity by using an MTT assay, the inhibition of [(3)H]thymidine incorporation into DNA as well as Collagen synthesis inhibition, demonstrated that these sulfonamides exhibit cytotoxic effects on breast Cancer cell lines ex vivo.
Keywords
Carbonic anhydrase inhibitors; Cytotoxicity; MCF-7; MDA-MB-231; Pyrazolo[4,3-e][1,2,4]triazine; Sulfonamides.