Deacetylravidomycin (syn: O-Deacetylravidomycin) is the more active and stable analog of the ravidomycin complex produced by Streptomyces ravidus. The metabolite shows potent, light-dependent antitumor activity. Deacetylravidomycin, like the related gilvocarcins and chrysomycins, is thought to act as a topoisomerase II inhibitor. The compound exhibits light-dependent antibacterial and anti-cancer activities.
Deacetylravidomycin is soluble in DMF and DMSO and is moderately soluble in methanol and ethanol.
| Mechanism of Action |
Deacetylravidomycin, like the related gilvocarcins and chrysomycins, is thought to act as a topoisomerase II inhibitor. It is a potent photosensitizing, DNA-damaging agent. |
| Cancer Applications |
Deacetylravidomycin was produced along with Ravidomycin in a culture medium containing sodium anthraquinone-beta-sulfonate when Streptomyces ravidus S50905 was grown. A new compound called deacetylravidomycin N-oxide was also formed. The structure was determined from NMR and mass spectrometric data, and further confirmed by chemical synthesis from deacetylravidomycin. It was found to have antitumor properties and was active against P388 leukemia and Meth A fibrosarcoma in a wide range of concentrations and was considerably less toxic than Deacetylravidomycin. Its antibacterial activity was less potent than deacetylravidomycin (Narita at al, 1989). |
| Eukaryotic Cell Culture Applications |
Deacetylravidomycin was studied using the lambda prophage induction assay. induction of the enzyme beta-galactosidase is measured as an indication of the ability of a compound to directly or indirectly damage DNA. Light in both the near UV and visible wave length ranges activated both Deacetylravidomycin and ravidomycin. Near UV and visible blue wavelengths were most effective, while 597-nm light was totally ineffective. The amount of induction varied directly with the dosage of light. Growth inhibition, along with cytotoxicity of a human colon carcinoma cell line was also enhanced dramatically by light. This data suggest that Deacetylravidomycin (and ravidomycin) are potent photosensitizing, DNA-damaging agents (Greenstein et al, 1986). |
| References |
Greenstein M et al (1986) Light-dependent activity of the antitumor antibiotics ravidomycin and Desacetylravidomycin. Antimicrob. Agents Chemother. 29:861 Lorico A et al (1993) Biochemical characterisation of elsamicin and other coumarin-related antitumor agents as potent inhibitors of human topoisomerase II. Eur. J. Cancer 29A:1985 Narita T et al (1989) Deacetylravidomycin N-oxide, a new antibiotic. Taxonomy and fermentation of the producing organism and isolation, structure and biological properties of the antibiotic. J. Antibiot (Tokyo). 42(3):347-356 PMID 2708127 Rakhit S et al (1986) Chemical modification of ravidomycin and evaluation of biological activities of its derivatives. Antimicrob. Agents Chemother. 29:861 Yamashita N et al (1998) New ravidomycin analogues, FE35A and FE35B, apoptosis inducers produced by Streptomyces rochei. J. Antibiot. 51:1105 |