6533b7dafe1ef96bd126edcc
RESEARCH PRODUCT
Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a gammadelta-T lymphocytes-mediated activation mechanism.
Daniele SimoniAaron KwaasiRiccardo BaruchelloJames E. DunfordCarla MarchioroL. MarinelliFrancesco DieliSimona BuccheriStefano ProveraNadia CaccamoNicola GebbiaFrancesco Paolo InvidiataEttore NovellinoRiccardo RondaninPaolo MarchettiManlio TolomeoMarco EleopraVittorio Limongellisubject
T cellAntineoplastic AgentsApoptosisMice SCIDLymphocyte ActivationMiceStructure-Activity RelationshipAntigenIn vivoCell Line TumorDrug DiscoverymedicineAnimalsHumansStructure–activity relationshipAminesCytotoxicityDiphosphonatesMolecular StructureChemistryReceptors Antigen T-Cell gamma-deltaBiological activityIn vitromedicine.anatomical_structureBiochemistryMechanism of actionDrug DesignCancer researchMolecular Medicinemedicine.symptomaminobisphosphonates gammadelta-T lymphocytesdescription
A small series of aminobisphosphonates (N-BPs) structurally related to zoledronic acid was synthesized with the aim of improving activity toward activation of human gammadelta T cells and in turn their in vivo antitumor activity. The absence of the 1-OH moiety, together with the position and the different basicity of the nitrogen, appears crucial for antitumor activity. In comparison to zoledronic acid, compound 6a shows a greater ability to activate gammadelta T cells expression (100 times more) and a proapoptotic effect that is better than zoledronic acid. The potent activation of gammadelta T cells, in addition to evidence of the in vivo antitumor activity of 6a, suggests it may be a new potential drug candidate for cancer treatment.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2008-01-01 |