title: Synthesis and Biological Evaluation of Pyrazolo[3,4-b]pyridin-4-ones as a New Class of Topoisomerase II Inhibitors.
abstract: A series of 1,3,6-triphenylpyrazolo[3,4-b]pyridin-4-one derivatives was designed, synthesized and evaluated for cytotoxic activity in A375 human melanoma and human erythroleukemia (HEL) cells. The new pyrazolopyridones displayed comparable activities to the antitumor compound etoposide. The inhibitory effect of compounds 17, 18, 27 and 32 against topoisomerase II-mediated cleavage activities was measured finding good correlation with the results obtained from MTS assay. Docking studies into bacterial topoisomerase II (DNA Gyrase), topoisomerase IIα and topoisomerase IIβ binding sites in the DNA binding interface were performed.
authors.forename: Mojgan Aghazadeh
authors.initials: MA
authors.lastname: Tabrizi
authors.forename: Pier Giovanni
authors.initials: PG
authors.lastname: Baraldi
authors.forename: Stefania
authors.initials: S
authors.lastname: Baraldi
authors.forename: Filippo
authors.initials: F
authors.lastname: Prencipe
authors.forename: Delia
authors.initials: D
authors.lastname: Preti
authors.forename: Giulia
authors.initials: G
authors.lastname: Saponaro
authors.forename: Romeo
authors.initials: R
authors.lastname: Romagnoli
authors.forename: Stefania
authors.initials: S
authors.lastname: Gessi
authors.forename: Stefania
authors.initials: S
authors.lastname: Merighi
authors.forename: Angela
authors.initials: A
authors.lastname: Stefanelli
authors.forename: Debora
authors.initials: D
authors.lastname: Fazzi
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Borea
authors.forename: Rodolfo Couto
authors.initials: RC
authors.lastname: Maia
authors.forename: Nelilma C
authors.initials: NC
authors.lastname: Romeiro
authors.forename: Carlos A M
authors.initials: CA
authors.lastname: Fraga
authors.affiliation: Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Via Fossato di Mortara 17- 19, 44121, Ferrara, Italy.
authors.forename: Eliezer J
authors.initials: EJ
authors.lastname: Barreiro
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000037:antagonists & inhibitors / Q000737:chemistry; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D062105:Molecular Docking Simulation; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011728:Pyridones / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D011720:Pyrazoles; D011728:Pyridones; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; D004247:DNA; D004250:DNA Topoisomerases, Type II