title: The discovery of new cytotoxic pyrazolopyridine derivatives.
abstract: A number of new 3,7-disubstituted pyrazolo[3,4-c]pyridines have been designed and synthesized from suitable 2-aminopyridines. The antiproliferative activity of the derivatives was determined against the pancreatic MIA PaCa-2 and ovarian SCOV3 cancer cell-lines. IC50values of the most promising analogue 46 lie in the submicromolar or low micromolar range. Furthermore, compound 46 shows similar inhibitory activities against DU145, A2058 and PC-3 cancer cells, blocks the cell cycle at the G0/G1phase and induce apoptosis, as determined by the appearance of apoptotic nuclei.
authors.affiliation: Division of Pharmaceutical Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis-Zografou, Athens 15771, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Giannouli
authors.affiliation: Division of Pharmaceutical Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis-Zografou, Athens 15771, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Lougiakis
authors.affiliation: Division of Pharmaceutical Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis-Zografou, Athens 15771, Greece.
authors.forename: Ioannis K
authors.initials: IK
authors.lastname: Kostakis
authors.affiliation: Division of Pharmaceutical Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis-Zografou, Athens 15771, Greece.
authors.forename: Nicole
authors.initials: N
authors.lastname: Pouli
authors.affiliation: Division of Pharmaceutical Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis-Zografou, Athens 15771, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Marakos
authors.affiliation: Division of Pharmacognosy & Natural Products Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis-Zografou, Athens 15771, Greece.
authors.forename: Alexios-Leandros
authors.initials: AL
authors.lastname: Skaltsounis
authors.affiliation: Beckman Research Institute, Comprehensive Cancer Center City of Hope, Los Angeles, USA.
authors.forename: Sangkil
authors.initials: S
authors.lastname: Nam
authors.affiliation: NSU Cell Therapy Institute, Nova Southeastern University, Fort Lauderdale, FL, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Jove
authors.affiliation: Beckman Research Institute, Comprehensive Cancer Center City of Hope, Los Angeles, USA.
authors.forename: David
authors.initials: D
authors.lastname: Horne
authors.affiliation: Department of Science of Nutrition & Dietetics, Harokopio University, 70 El. Venizelou Street, Athens 17671, Greece.
authors.forename: Roxane
authors.initials: R
authors.lastname: Tenta
authors.affiliation: Laboratory of Cell Proliferation and Ageing, Institute of Biosciences & Applications, NCSR ''Demokritos", 15310 Athens, Greece.
authors.forename: Harris
authors.initials: H
authors.lastname: Pratsinis
authors.affiliation: Laboratory of Cell Proliferation and Ageing, Institute of Biosciences & Applications, NCSR ''Demokritos", 15310 Athens, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kletsas
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D055808:Drug Discovery; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D011720:Pyrazoles; D011725:Pyridines; C118531:pyrazolopyridine
keywords: Antiproliferative activity; Cell-cycle selectivity; Deazapurines; Pyrazolo[3,4-c]pyridine; Suzuki coupling