title: Novel juglone and plumbagin 5-O derivatives and their in vitro growth inhibitory activity against apoptosis-resistant cancer cells.
abstract: Juglone 1 an plumbagin 2 are plant secondary metabolites nowadays well known for their anticancer properties. In this study we synthesized analogues of 1 and 2 deriving from the functionalization of the OH group in position 5 with different side chains in form of esters and ethers. Therefore the growth inhibitory activities of these adducts were evaluated in vitro on six cancer cell lines using the MTT colorimetric assays along with the two natural parent compounds. The data revealed that these latter displayed the strongest growth inhibitory activities in vitro. Quantitative videomicroscopy analyses were then carried out on human U373 glioblastoma cells, which are characterized by various level of resistance to pro-apoptotic stimuli. We compared the naturally occurring reference compounds 1 and 2 with the derivatives exerting the best activities in terms of IC50 growth inhibitory values. These analyses showed that both juglone and plumbagin had a cytostatic effect on U373 cells and were able to overcome the intrinsic resistance of U373 cancer cells to pro-apoptotic stimuli.
authors.affiliation: Dipartimento di Farmacia, Università 'G. D'Annunzio' Chieti-Pescara, Via dei Vestini 31, 66100 Chieti Scalo (CH), Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Fiorito
authors.affiliation: Dipartimento di Farmacia, Università 'G. D'Annunzio' Chieti-Pescara, Via dei Vestini 31, 66100 Chieti Scalo (CH), Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Genovese
authors.affiliation: Dipartimento di Farmacia, Università 'G. D'Annunzio' Chieti-Pescara, Via dei Vestini 31, 66100 Chieti Scalo (CH), Italy.
authors.forename: Vito Alessandro
authors.initials: VA
authors.lastname: Taddeo
authors.affiliation: Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles, 1050 Brussels, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Mathieu
authors.affiliation: Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles, 1050 Brussels, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
authors.affiliation: Dipartimento di Farmacia, Università 'G. D'Annunzio' Chieti-Pescara, Via dei Vestini 31, 66100 Chieti Scalo (CH), Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Epifano
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D009285:Naphthoquinones; C005134:juglone; C014758:plumbagin
keywords: 1,4-Naphthoquinones; Cancer; In vitro growth inhibition; Juglone; Plumbagin