title: Antiproliferative activity of Juglone derivatives on rat glioma.
abstract: Malignant gliomas are aggressive and life-threatening tumours that still show a poor prognosis: the current therapeutic approach based on surgical resection and chemotherapy combined with radiotherapy does not provide a satisfactory chance of long-term survival to patients. Natural bioactive compounds represent a precious source of molecules with antiproliferative activity, potentially effective also against glioma cells. Among these, Juglone is a known allelopathic compound extracted from the eastern black walnut (Juglans nigra) whose antimitotic effect has been extensively described in mammalian cells. We investigated the antiproliferative effect of a synthetic derivative of this natural compound, 2-(2,4-dihydroxyphenyl)-8-hydroxy-1,4-naphthoquinone (DiNAF), in rat glioma cells. We compared this molecule and its effect with the natural reference compound and with newly synthesised derivatives to build a preliminar structure-activity relationship. Biological assays and NMR-based redox experiments confirmed that DiNAF is a promising lead and supported the hypothesis of a redox mechanism underlying its cytotoxic activity.
authors.affiliation: a Department of Pharmaceutical and Pharmacological Sciences , University of Padova , Padova , Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Pavan
authors.affiliation: a Department of Pharmaceutical and Pharmacological Sciences , University of Padova , Padova , Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ribaudo
authors.affiliation: b Department of Molecular Medicine , University of Padova , Padova , Italy.
authors.forename: Maira
authors.initials: M
authors.lastname: Zorzan
authors.affiliation: b Department of Molecular Medicine , University of Padova , Padova , Italy.|d AIROB , Italian Association for Basic Oncological Research , Padova , Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Redaelli
authors.affiliation: c Department of Medical and Surgical Sciences-Operative Unit of Endocrinology , University of Padova , Padova , Italy.|d AIROB , Italian Association for Basic Oncological Research , Padova , Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Pezzani
authors.affiliation: b Department of Molecular Medicine , University of Padova , Padova , Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Mucignat-Caretta
authors.affiliation: a Department of Pharmaceutical and Pharmacological Sciences , University of Padova , Padova , Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zagotto
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy*; D031324:Juglans / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008938:Mitosis / Q000187:drug effects; D008958:Models, Molecular; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009285:Naphthoquinones; C005134:juglone
keywords: Glioma; Juglone; TMZ; naphthoquinones