title: Synthesis and cytotoxicity of leinamycin antibiotic analogues.
abstract: A simple synthesis of 1,2-dithiolan-3-ones from alpha,beta-unsaturated thiophenyl esters is reported. Introduction of the biologically active 1,2-dithiolan-3-one-1-oxide moiety of leinamycin into aldehydo-d-arabinose 11, the uridine derivative 16, and the deoxythymidine 21 was established. An extended bioactive part of leinamycin carrying a carbon-carbon triple bond was also synthesized. All of these analogues of leinamycin showed cytotoxic activity against HeLa3 tumor cells. Interestingly, the lipophilic, silyl group-containing derivatives proved to be more active than the hydrophilic counterparts.
authors.affiliation: Department of Pharmaceutical Chemistry and Research Group for Antibiotics of the Hungarian Academy of Sciences, University of Debrecen, Egyetem tér 1, P.O. Box 70 H-4010 Debrecen, Hungary.
authors.forename: Akos
authors.initials: A
authors.lastname: Szilagyi
authors.forename: Ferenc
authors.initials: F
authors.lastname: Fenyvesi
authors.forename: Orsolya
authors.initials: O
authors.lastname: Majercsik
authors.forename: Istvan F
authors.initials: IF
authors.lastname: Pelyvas
authors.forename: Ildikó
authors.initials: I
authors.lastname: Bacskay
authors.forename: Palma
authors.initials: P
authors.lastname: Fehér
authors.forename: Judit
authors.initials: J
authors.lastname: Varadi
authors.forename: Miklós
authors.initials: M
authors.lastname: Vecsernyés
authors.forename: Pal
authors.initials: P
authors.lastname: Herczegh
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013871:Thiones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D007769:Lactams; D018942:Macrolides; D013844:Thiazoles; D013871:Thiones; C059000:leinamycin