title: Phenylpyrazolo[1,5-a]quinazolin-5(4H)-one: a suitable scaffold for the development of noncamptothecin topoisomerase I (Top1) inhibitors.
abstract: In search for a novel chemotype to develop topoisomerase I (Top1) inhibitors, the pyrazolo[1,5-a]quinazoline nucleus, structurally related to the indenoisoquinoline system precursor of well-known Top1 poisons, was variously decorated (i.e., a substituted phenyl ring at 2- or 3-position, a protonable side chain at 4- or 5-position), affording a number of Top1 inhibitors with cleavage patterns common to CPT and MJ-III-65. SARs data were rationalized by means of an advanced docking protocol.
authors.affiliation: Department of Pharmacy, University of Pisa , via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Taliani
authors.forename: Isabella
authors.initials: I
authors.lastname: Pugliesi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Barresi
authors.forename: Silvia
authors.initials: S
authors.lastname: Salerno
authors.forename: Christophe
authors.initials: C
authors.lastname: Marchand
authors.forename: Keli
authors.initials: K
authors.lastname: Agama
authors.forename: Francesca
authors.initials: F
authors.lastname: Simorini
authors.forename: Concettina
authors.initials: C
authors.lastname: La Motta
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Marini
authors.forename: Francesco Saverio
authors.initials: FS
authors.lastname: Di Leva
authors.forename: Luciana
authors.initials: L
authors.lastname: Marinelli
authors.forename: Sandro
authors.initials: S
authors.lastname: Cosconati
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Yves
authors.initials: Y
authors.lastname: Pommier
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Santo
authors.forename: Federico
authors.initials: F
authors.lastname: Da Settimo
mesh_terms: D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000378:metabolism*; D055808:Drug Discovery; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D011758:Pyrroles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011799:Quinazolines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D059004:Topoisomerase I Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D006575:Heterocyclic Compounds, 3-Ring; D011758:Pyrroles; D011799:Quinazolines; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I