1. Synthesis and cytotoxicity of leinamycin antibiotic analogues.
- Author
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Szilagyi A, Fenyvesi F, Majercsik O, Pelyvas IF, Bacskay I, Fehér P, Varadi J, Vecsernyés M, and Herczegh P
- Subjects
- Antibiotics, Antineoplastic chemistry, Antibiotics, Antineoplastic pharmacology, Drug Screening Assays, Antitumor, HeLa Cells, Humans, Lactams chemistry, Lactams pharmacology, Macrolides chemistry, Macrolides pharmacology, Structure-Activity Relationship, Thiazoles chemistry, Thiazoles pharmacology, Thiones chemistry, Thiones pharmacology, Antibiotics, Antineoplastic chemical synthesis, Lactams chemical synthesis, Macrolides chemical synthesis, Thiazoles chemical synthesis, Thiones chemical synthesis
- 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.
- Published
- 2006
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