Pyrazolo[4,3-e][1,2,4]triazine sulfonamides as carbonic anhydrase inhibitors with antitumor activity.
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.
Department of Chemistry, Siedlce University of Natural Sciences and Humanities, 3-go Maja 54, 08-110 Siedlce, Poland. Electronic address: mmojzych@yahoo.com.
Mariusz
M
Mojzych
Department of Medicinal Chemistry and Drug Technology, Medical University of Bialystok, Bialystok, Poland.
Anna
A
Bielawska
Department of Medicinal Chemistry and Drug Technology, Medical University of Bialystok, Bialystok, Poland.
Krzysztof
K
Bielawski
Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
Mariangela
M
Ceruso
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: claudiu.supuran@unifi.it.
Claudiu T
CT
Supuran
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D011720:Pyrazoles / Q000737:chemistry*; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D014227:Triazines / Q000737:chemistry*
D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D014227:Triazines; C031280:pyrazole; D002256:Carbonic Anhydrases
Carbonic anhydrase inhibitors; Cytotoxicity; MCF-7; MDA-MB-231; Pyrazolo[4,3-e][1,2,4]triazine; Sulfonamides