FR182876, a new microtubule modulator with high water-solubility, from a Streptomyces.

Abstract

In the course of seeking new anti-tumor drugs, a new microtubule modulator with high water-solubility, FR182876, was isolated from a Streptomyces which also produces FR182877. Even modern spectroscopic methods could not solve the structure of FR182876 due to its structural complexity and chemical instability. Thus, we have combined chemical correlations with spectroscopic methods and determined its structure, which features a highly fused ring system and 3-methylhistidine. The latter is believed to contribute to both solubility in water and activity in promoting tubulin polymerization. FR182876 showed potent cytotoxicity against a panel of cancer cells at concentrations of 28-75 ng/ml.

• Authors: Seiji Yoshimura, Bunji Sato, Shigehiro Takase, Hiroshi Terano
• Journal: The Journal of antibiotics (J Antibiot (Tokyo)) Vol. 57 Issue 7 Pg. 429-35 (Jul 2004) ISSN: 0021-8820 [Print] England
• PMID: 15376555 (Publication Type: Journal Article)

Chemical References

• Antibiotics, Antineoplastic
• FR 182876
• Heterocyclic Compounds, 4 or More Rings

Topics

• Antibiotics, Antineoplastic (chemistry, isolation & purification, pharmacology)
• Cell Line, Tumor
• Heterocyclic Compounds, 4 or More Rings (chemistry, isolation & purification, pharmacology)
• Humans
• Microtubules (drug effects)
• Solubility
• Streptomyces (metabolism)