title: Stabilization of the cyclodecadiene derivative isofuranodiene by silver (I) coordination. Mechanistic and biological aspects.
abstract: The industrial extraction and further applications of isofuranodiene are limited because at room temperature it spontaneously converts to curzerene, a structurally less active isomer. This work definitively identified the structure of isofuranodiene in the solid state, showing the two methyl groups in syn position. In addition, two bioactive metal cations, namely, silver(I) and copper(II) ions, were used in the attempt to obtain the chemical stability of isofuranodiene: in the case of silver(I), a labile adduct was formed, while in the case of copper(II), a more stable 1:1 adduct was achieved. In the former, the presence of silver did not significantly affect the biological activities of isofuranodiene, while in the latter, the copper(II) coordination suppressed them. The biological activities of the isofuranodiene adducts were then evaluated as antiproliferative agents against human tumor cell lines (HCT116, MDA-MB 231, and T98G). In addition, for the first time, isofuranodiene was tested as an inhibitor of DHFR (DiHydroFolateReductase) from Escherichia coli. Anticancer activity was observed in the isofuranodiene with the AgCF3SO3adduct, in the tested cell lines, with IC50values ranging from 4.89μM to 13.06μM, while inhibition assays highlighted a Ki of 6.22μM for isofuranodiene and of 0.17μM for the related silver adduct. Docking studies indicated a binding mode score of -6.83Kcal/mol for isofuranodiene, and an energy value of -11.82Kcal/mol for methotrexate (a classic DHFR inhibitor).
authors.affiliation: School of Pharmacy, University of Camerino, Via S. Agostino, 1, I-62032 Camerino, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Maggi
authors.affiliation: School of Science and Technology, Chemistry Division, University of Camerino, Via S. Agostino, 1, I-62032 Camerino, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Papa
authors.affiliation: School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, I-62032 Camerino, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pucciarelli
authors.affiliation: School of Pharmacy, University of Camerino, Via S. Agostino, 1, I-62032 Camerino, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bramucci
authors.affiliation: School of Pharmacy, University of Camerino, Via S. Agostino, 1, I-62032 Camerino, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Quassinti
authors.affiliation: School of Science and Technology, Chemistry Division, University of Camerino, Via S. Agostino, 1, I-62032 Camerino, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Barboni
authors.affiliation: School of Pharmacy, University of Camerino, Via S. Agostino, 1, I-62032 Camerino, Italy.
authors.forename: Diego Dal
authors.initials: DD
authors.lastname: Ben
authors.affiliation: School of Science and Technology, Chemistry Division, University of Camerino, Via S. Agostino, 1, I-62032 Camerino, Italy.
authors.forename: Anna Teresa
authors.initials: AT
authors.lastname: Ramadori
authors.affiliation: Dipartimento di Chimica, Università di Parma, Viale delle Scienze 17/A, 43100 Parma, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Graiff
authors.affiliation: School of Science and Technology, Chemistry Division, University of Camerino, Via S. Agostino, 1, I-62032 Camerino, Italy. Electronic address: rossana.galassi@unicam.it.
authors.forename: Rossana
authors.initials: R
authors.lastname: Galassi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry; D004926:Escherichia coli / Q000201:enzymology; D005493:Folic Acid Antagonists / Q000737:chemistry*; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D012834:Silver / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D005663:Furans; D012834:Silver; C017897:isofuranodiene; D003300:Copper
keywords: Cytotoxicity; DihydroFolateReductase; Docking study; Isofuranodiene; Silver adduct; Smyrnium olusatrum