title: New approaches to the synthesis of sildenafil analogues and their enzyme inhibitory activity.
abstract: In the search for new biologically active chemotypes, several sildenafil analogs were prepared and characterized. The presence of the pyrazolo[4,3-e][1,2,4]triazine core is thought to be of interest for the enzyme inhibitory activity of these compounds. The designed derivatives incorporating the sildenafil scaffold were assayed as carbonic anhydrase inhibitors, and for their cytotoxic activity against MCF-7 and K562 cell lines. The X-ray analysis of one of these model compounds was performed and its crystal structure is described/compared to that of sildenafil.
authors.affiliation: Department of Chemistry, Siedlce University of Natural Sciences and Humanities, 3 Maja 54, 08-110 Siedlce, Poland. Electronic address: mmojzych@yahoo.com.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Mojzych
authors.affiliation: Department of Chemistry, Siedlce University of Natural Sciences and Humanities, 3 Maja 54, 08-110 Siedlce, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Karczmarzyk
authors.affiliation: Department of Chemistry, Siedlce University of Natural Sciences and Humanities, 3 Maja 54, 08-110 Siedlce, Poland.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Wysocki
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Ceruso
authors.affiliation: 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.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.affiliation: Laboratory of Growth Regulators, Faculty of Science, Palacký University & Institute of Experimental Botany AS CR, Šlechtitelů 11, 78371 Olomouc, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kryštof
authors.affiliation: Università degli Studi di Firenze, NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Urbańczyk-Lipkowska
authors.affiliation: Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
authors.forename: Przemysław
authors.initials: P
authors.lastname: Kalicki
mesh_terms: D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D006801:Humans; D020014:K562 Cells; D061986:MCF-7 Cells; D058986:Phosphodiesterase 5 Inhibitors / Q000138:chemical synthesis; D000068677:Sildenafil Citrate / Q000031:analogs & derivatives* / Q000138:chemical synthesis*
chemical_list: D004791:Enzyme Inhibitors; D058986:Phosphodiesterase 5 Inhibitors; D000068677:Sildenafil Citrate
keywords: DFT calculations; Pyrazolo[4,3-e][1,2,4]triazine; Sildenafil analogues; Sulfonamides; X-ray structure analysis