title: Synthesis and biological activity of 8-azapurine and pyrazolo[4,3-d]pyrimidine analogues of myoseverin.
abstract: The trisubstituted purine myoseverin has been recently identified as a novel inhibitor of microtubule assembly. To analyze the effects of modifying its heterocyclic skeleton, we prepared 8-azapurine and pyrazolo[4,3-d]pyrimidine analogues of myoseverin and compared their biological activities. Rearrangement of nitrogen atoms in the heterocycle changes the affinity of the compounds to purified tubulin, as demonstrated by the results of polymerization assays, and affects the proliferation of cancer cell lines. Surprisingly, compound E2GG, a pyrazolo[4,3-d]pyrimidine analogue of myoseverin, displayed inhibitory activity towards both tubulin polymerization and the activity of cyclin-dependent kinases 1, 2 and 7. Such a dual specificity-inhibitor offers a starting point for developing a novel class of antiproliferative agents.
authors.affiliation: Laboratory of Growth Regulators, Faculty of Science, Palacký University & Institute of Experimental Botany AS CR, Slechtitelů 11, 783 71 Olomouc, Czech Republic. krystof@prfholnt.upol.cz
authors.forename: Vladimír
authors.initials: V
authors.lastname: Krystof
authors.forename: Daniela
authors.initials: D
authors.lastname: Moravcová
authors.forename: Martina
authors.initials: M
authors.lastname: Paprskárová
authors.forename: Pascale
authors.initials: P
authors.lastname: Barbier
authors.forename: Vincent
authors.initials: V
authors.lastname: Peyrot
authors.forename: Alice
authors.initials: A
authors.lastname: Hlobilková
authors.forename: Libor
authors.initials: L
authors.lastname: Havlícek
authors.forename: Miroslav
authors.initials: M
authors.lastname: Strnad
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D011687:Purines; D011720:Pyrazoles; D011743:Pyrimidines; C407365:myoseverin; C014175:pyrazolo(3,4-d)pyrimidine; C015008:triazolopyrimidinone