Synthesis and cytotoxicity of leinamycin antibiotic analogues

J Med Chem. 2006 Sep 7;49(18):5626-30. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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