title: Heteroannelated and 7-deoxygenated goniofufurone mimics with antitumour activity: design, synthesis and preliminary SAR studies.
abstract: Cytotoxic (+)-goniofufurone mimic such as benzoxepane 2 was preferentially formed after the treatment of 7-O-benzoyl-5-O-benzyl (+)-goniofufurone derivative 6 with titanium(IV) fluoride. However, the corresponding 7-epimer 5 (derivative of 7-epi-goniofufurone) under the similar reaction conditions gave mainly 7-deoxy derivative 7 as a result of an unexpected 1,5-hydride shift. Extension of this methodology to the enantiomer ent-6 provided cytotoxic (-)-goniofufurone mimics ent-2 and ent-7. Synthesized compounds showed diverse growth inhibitory effects against selected tumour cell lines, but were devoid of any significant toxicity towards the normal foetal lung fibroblasts (MRC-5). A SAR study reveals the structural features of these lactones that are beneficial for their antiproliferative activity, such as presence of an additional oxepane ring, the absolute stereochemistry and the presence of a deoxy function at the C-7 position.
authors.affiliation: Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia. Electronic address: velimir.popsavin@dh.uns.ac.rs.
authors.forename: Velimir
authors.initials: V
authors.lastname: Popsavin
authors.forename: Jovana
authors.initials: J
authors.lastname: Francuz
authors.forename: Bojana
authors.initials: B
authors.lastname: Srećo Zelenović
authors.forename: Goran
authors.initials: G
authors.lastname: Benedeković
authors.forename: Mirjana
authors.initials: M
authors.lastname: Popsavin
authors.forename: Vesna
authors.initials: V
authors.lastname: Kojić
authors.forename: Gordana
authors.initials: G
authors.lastname: Bogdanović
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003500:Cyclization; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005459:Fluorides / Q000737:chemistry; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014025:Titanium / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D007783:Lactones; C073080:7-goniofufurone; D014025:Titanium; D005459:Fluorides; C032240:titanium tetrafluoride
keywords: Analogue synthesis; Antitumour styryl lactones; Goniofufurone mimics; SAR; Titanium(IV) fluoride