title: Discovery of novel small-molecule compounds with selective cytotoxicity for Burkitt's lymphoma cells using 3D ligand-based virtual screening.
abstract: We describe a ligand-based approach towards compounds with more specific targeting for Burkitt's lymphoma. Using three-dimensional ligand-based similarity searches and a previously described hit compound, we have identified six compounds that are chemically different but with similar spatial conformations. Biological evaluation revealed that one compound has better growth inhibition and improved selectivity towards Burkitt's lymphoma cells than the query compound. However, initial mechanism-of-action studies show a different target profile in comparison with the previous hit compound, which does not involve the inhibition of the proteasome or the NFκB pathway. The data from this study provide a solid basis for further efforts in the search for selective agents against Burkitt's lymphoma.
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Aškerčeva cesta 7, Ljubljana 1000, Slovenia. martina.gobec@ffa.uni-lj.si.
authors.forename: Martina
authors.initials: M
authors.lastname: Gobec
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Aškerčeva cesta 7, Ljubljana 1000, Slovenia. izidor.sosic@ffa.uni-lj.si.
authors.forename: Izidor
authors.initials: I
authors.lastname: Sosič
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Aškerčeva cesta 7, Ljubljana 1000, Slovenia. boris.brus@ffa.uni-lj.si.
authors.forename: Boris
authors.initials: B
authors.lastname: Brus
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Aškerčeva cesta 7, Ljubljana 1000, Slovenia. ales.obreza@ffa.uni-lj.si.
authors.forename: Aleš
authors.initials: A
authors.lastname: Obreza
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Aškerčeva cesta 7, Ljubljana 1000, Slovenia. stanislav.gobec@ffa.uni-lj.si.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Gobec
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Aškerčeva cesta 7, Ljubljana 1000, Slovenia. irena.mlinaric@ffa.uni-lj.si.
authors.forename: Irena
authors.initials: I
authors.lastname: Mlinarič-Raščan
mesh_terms: D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D008024:Ligands; D016328:NF-kappa B / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D008024:Ligands; D016328:NF-kappa B; D054852:Small Molecule Libraries; D046988:Proteasome Endopeptidase Complex