Phenylpyrazolo[1,5-a]quinazolin-5(4H)-one: a suitable scaffold for the development of noncamptothecin topoisomerase I (Top1) inhibitors.

Sabrina Taliani (1) , Isabella Pugliesi (1) , Elisabetta Barresi (1) , Silvia Salerno (1) , Christophe Marchand (2) , Keli Agama (2) , Francesca Simorini (1) , Concettina La Motta (1) , Anna Maria Marini (1) , Francesco Saverio Di Leva , Luciana Marinelli , Sandro Cosconati (3) , Ettore Novellino (4) , Yves Pommier (5) , Roberto Di Santo (6) , Federico da Settimo (1)

1 Department of Pharmacy
2 Laboratory of Molecular Pharmacology
3 Department of Pharmaceutical Chemistry and Toxicology
4 Department of Pharmacy Naples
5 Laboratory of Molecular Pharmacology
6 Department of Medicinal Chemistry and Technologies

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.

Domains: Life Sciences [q-bio]; Pharmaceutical sciences

Sabrina Taliani, Isabella Pugliesi, Elisabetta Barresi, Silvia Salerno, Christophe Marchand, et al.. Phenylpyrazolo[1,5-a]quinazolin-5(4H)-one: a suitable scaffold for the development of noncamptothecin topoisomerase I (Top1) inhibitors.. Journal of Medicinal Chemistry, 2013, 56 (18), pp.7458-62. ⟨10.1021/jm400932c⟩. ⟨pasteur-00968854⟩