Synthesis and cytotoxicity of leinamycin antibiotic analogues

  • J Med Chem. 2006 Sep 7;49(18):5626-30. doi: 10.1021/jm060471h.
Akos Szilagyi  1 ,  Ferenc Fenyvesi ,  Orsolya Majercsik ,  Istvan F Pelyvas ,  Ildikó Bacskay ,  Palma Fehér ,  Judit Varadi ,  Miklós Vecsernyés ,  Pal Herczegh
Affiliations
  • 1. 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.
PMID: 16942037 DOI: 10.1021/jm060471h
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.