6533b85ffe1ef96bd12c1b7a
RESEARCH PRODUCT
1-methil-3H-pyrazolo[1-2-a]benzo[1-2-3-4]tetrazin-3-ones, design synthesis and biological activity of new antitumoral agents
Girolamo CirrincioneAntonino LauriaPatrizia DianaAnna Maria AlmericoFrancesco MingoiaGaetano DattoloAlessandra MontalbanoPaola Barrajasubject
antiproliferative activityQuantitative structure–activity relationshipStereochemistry2-a]benzotetrazinoneQuantitative Structure-Activity RelationshipRifamycinsAntineoplastic Agents1-Methylpyrazolo[12-a]benzo[1234]tetrazin-3-oneChemical synthesischemistry.chemical_compoundantiproliferativeCell Line TumorDrug DiscoveryCOMPARE and 3D-MIND analysisHumansComputer Simulationpyrazolo[1CytotoxicityBiological activityCytidinechemistryDrug Designantitumor agentMolecular MedicinePyrazolesDrug Screening Assays AntitumorSelectivityHeterocyclic Compounds 3-RingMethyl groupdescription
1-Methylpyrazolo[1,2-a]benzo[1,2,3,4]tetrazin-3-ones 4, synthesized in good to excellent yields, were designed as novel alkylating agents because of their peculiar chemical behavior. All derivatives showed antiproliferative activity against more than 50 types of tumor cell lines with GI50 reaching sub-micromolar values. SAR studies revealed that the presence of a chlorine atom is well-tolerated in both positions 8 and 9, whereas in the case of the methyl group, switching from the 8 to the 9 position gives rise to the most active compound of the series, 4g, either for the number of cell lines inhibited and for selectivity against leukaemia and renal cancer subpanels. COMPARE and 3D-MIND computations indicate, for compounds 4, an activity profile analogous to rifamycins and cytidine analogues.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2005-01-01 |