title: The synthesis and anticancer activity of analogs of the indole phytoalexins brassinin, 1-methoxyspirobrassinol methyl ether and cyclobrassinin.
abstract: An effective synthesis of analogs of the indole phytoalexin cyclobrassinin with NR1R2 group instead of SCH3 was developed starting from indole-3-carboxaldehyde. The target compounds were prepared by spirocyclization of 1-Boc-thioureas with the formation of isolable spiroindoline intermediates, followed by the trifluoroacetic acid-induced cascade reaction consisting of methanol elimination, deprotection and rearrangement of the iminium ion. The structures of novel products were elucided by the (1)H and (13)C NMR spectroscopy, including HMBC, HSQC, COSY, NOESY and DEPT measurements. Several newly synthesized compounds demonstrated significant antiproliferative/cytotoxic activity against human leukemia and solid tumor cell lines, as well as remarkable selectivity of these effects against cancer cells relative to the non-malignant HUVEC cells.
authors.affiliation: Department of Organic Chemistry, Institute of Chemical Sciences, Faculty of Science, P.J. Šafárik University, Moyzesova 11, 040 01 Košice, Slovak Republic. Electronic address: mariana.budovska@upjs.sk.
authors.forename: Mariana
authors.initials: M
authors.lastname: Budovská
authors.forename: Martina
authors.initials: M
authors.lastname: Pilátová
authors.forename: Lenka
authors.initials: L
authors.lastname: Varinská
authors.forename: Ján
authors.initials: J
authors.lastname: Mojžiš
authors.forename: Roman
authors.initials: R
authors.lastname: Mezencev
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D019169:Jurkat Cells; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D012717:Sesquiterpenes / Q000737:chemistry*; D013237:Stereoisomerism; D013859:Thiocarbamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000094162:Phytoalexins
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D012717:Sesquiterpenes; D013859:Thiocarbamates; C581768:cyclobrassinin; C089020:brassinin; C012381:indole-3-carbaldehyde; C030374:indole; D000094162:Phytoalexins
keywords: Antiproliferative activity; Cyclobrassinin; Indoles; Phytoalexins; Spirocyclization