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: Akos Szilagyi, Ferenc Fenyvesi, Orsolya Majercsik, Istvan F Pelyvas, Ildikó Bacskay, Palma Fehér, Judit Varadi, Miklós Vecsernyés, Pal Herczegh
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 49 Issue 18 Pg. 5626-30 (Sep 07 2006) ISSN: 0022-2623 [Print] United States
• PMID: 16942037 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Lactams
• Macrolides
• Thiazoles
• Thiones
• leinamycin

Topics

• Antibiotics, Antineoplastic (chemical synthesis, chemistry, pharmacology)
• Drug Screening Assays, Antitumor
• HeLa Cells
• Humans
• Lactams (chemical synthesis, chemistry, pharmacology)
• Macrolides (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship
• Thiazoles (chemical synthesis, chemistry, pharmacology)
• Thiones (chemical synthesis, chemistry, pharmacology)