title: Synthesis and biological evaluation of simplified pironetin analogues with modifications in the side chain and the lactone ring.
abstract: The preparation of several new analogues of the natural dihydropyrone pironetin is described. They differ from the natural product mainly in the nature of the side chain and the lactone ring. Their cytotoxic activity has been measured. In addition, their interaction with tubulin, their ability to inhibit the secretion of the vascular endothelial growth factor (VEGF) and the expression of angiogenesis and telomerase-related genes have been determined. Unexpectedly, and unlike pironetin, the lactones studied in this work do not interact with tubulin. Two of the compounds have been found to downregulate the expression of the hTERT and VEGF genes. Furthermore, one of them causes an appreciably decrease in the secretion of the VEGF protein.
authors.affiliation: Depart. de Q. Inorgánica y Orgánica, Univ. Jaume I, Castellón, E-12071 Castellón, Spain. jmurga@uji.es.
authors.forename: Steven
authors.initials: S
authors.lastname: Roldán
authors.affiliation: Depart. de Q. Inorgánica y Orgánica, Univ. Jaume I, Castellón, E-12071 Castellón, Spain. jmurga@uji.es.
authors.forename: Adrià
authors.initials: A
authors.lastname: Cardona
authors.affiliation: Depart. de Q. Inorgánica y Orgánica, Univ. Jaume I, Castellón, E-12071 Castellón, Spain. jmurga@uji.es.
authors.forename: Laura
authors.initials: L
authors.lastname: Conesa
authors.affiliation: Depart. de Q. Inorgánica y Orgánica, Univ. Jaume I, Castellón, E-12071 Castellón, Spain. jmurga@uji.es.
authors.forename: Juan
authors.initials: J
authors.lastname: Murga
authors.affiliation: Depart. de Q. Inorgánica y Orgánica, Univ. Jaume I, Castellón, E-12071 Castellón, Spain. jmurga@uji.es.
authors.forename: Eva
authors.initials: E
authors.lastname: Falomir
authors.affiliation: Depart. de Q. Inorgánica y Orgánica, Univ. Jaume I, Castellón, E-12071 Castellón, Spain. jmurga@uji.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: Carda
authors.affiliation: Depart. de Q. Orgánica, Univ. de Valencia, E-46100 Burjassot, Valencia, Spain. alberto.marco@uv.es.
authors.forename: J Alberto
authors.initials: JA
authors.lastname: Marco
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008870:Microtubules / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D019098:Telomerase / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007783:Lactones; D011753:Pyrones; D014404:Tubulin; D042461:Vascular Endothelial Growth Factor A; C088446:pironetin; D019098:Telomerase