Synthesis and antitumor activity of analogues of the antitumor antibiotic chartreusin.

Abstract

First isolated in 1953 from a fermentation broth, chartreusin (1) has received renewed interest as a result of substantial antitumor activities recently demonstrated in several murine test systems. Poor water solubility frustrated formulation attempts, and rapid biliary excretion observed in mice made 1 an improbable candidate for clinical development but an excellent candidate for an analogue synthesis program. From a common intermediate, which was prepared from 1, three analogues were synthesized wherein the disaccharide moiety of 1 was systematically replaced with fucose (6), glucose (7), and the disaccharide maltose (8). Each of the three analogues had a cytotoxic potency against cultured L1210 cells which was equal to, or better than, that shown by 1. Based on the structural similarity with the parent, an improved water solubility, and a favorable accessibility through synthesis, maltoside 8 was choe P388 leukemia, 8 showed reproducible activity comparable to chartreusin at similar dose levels. Although 8 caused no observable toxic effects at therapeutic dose levels when given ip, neither 1 nor 8 produced active indications when administered subcutnaeously.

• Authors: M Takai, Y Uehara, J A Beisler
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 23 Issue 5 Pg. 549-53 (May 1980) ISSN: 0022-2623 [Print] United States
• PMID: 7381855 (Publication Type: Journal Article)

Chemical References

• Antibiotics, Antineoplastic
• Benzopyrans
• Glycosides
• chartreusin

Topics

• Animals
• Antibiotics, Antineoplastic (chemical synthesis)
• Benzopyrans
• Cell Survival (drug effects)
• Chemical Phenomena
• Chemistry
• Glycosides (chemical synthesis, pharmacology)
• Leukemia L1210 (drug therapy)
• Leukemia P388 (drug therapy)
• Mice
• Neoplasms, Experimental (drug therapy)
• Solubility