Light-dependent activity of the antitumor antibiotics ravidomycin and desacetylravidomycin

Abstract

The antitumor antibiotics ravidomycin and desacetylravidomycin were studied by the biochemical A prophage induction assay. In this assay, induction of the enzyme j8-galactosidase is measured as a specific indication of the ability of an agent to directly or indirectly damage DNA. Induction was observed only when these two antibiotics were irradiated with light in the presence of the indicator organism. Drug treated with light followed by incubation with the indicator organism in the dark did not cause induction. Light in both the near UV and visible wave length ranges activated these antibiotics; near UV and visible blue wavelengths were most effective, while 597-nm light was totally ineffective. The amount of induction caused by these drugs varied directly with the dosage of light provided. Bacterial growth inhibition, as well as cytotoxicity for a human colon carcinoma cell line, was also dramatically enhanced by light. These data suggest that ravidomycin and desacetylravidomycin are potent photosensitizing, DNA-damaging agents.

Cloning and Characterization of the Ravidomycin and Chrysomycin Biosynthetic Gene Clusters

“…[8] However, they differ in their C -glycosidically linked sugar moieties: ravidomycin V (RMV, 1 , also known as ravidomycin) possesses an amino pyranose, 4′- O -acetyl- d -ravidosamine, whereas chrysomycin V (CMV, 9 , also known as chrysomycin A) possesses a branched neutral pyranose, d -virenose. [4,9–11] RMV shows a broad range of biological activities, such as antibacterial and antitumor both in vivo and in vitro. [11] Such activities primarily arise from the inhibitory effect of 1 on bacterial DNA and RNA synthesis.…”

“…[4,9–11] RMV shows a broad range of biological activities, such as antibacterial and antitumor both in vivo and in vitro. [11] Such activities primarily arise from the inhibitory effect of 1 on bacterial DNA and RNA synthesis. [12] In addition, excellent cytotoxicity of 1 was reported for human colon carcinoma cell lines.…”

“…[12] In addition, excellent cytotoxicity of 1 was reported for human colon carcinoma cell lines. [1,11] Furthermore, 1 has been reported to act as potent inhibitor of human topoisomerase II . [13] Similarly, antitumor activities of CMV have been reported against various cancer cell lines.…”

Bioactive C-Glycosides from Bacterial Secondary Metabolism

“…It primarily acts by inhibiting the biosynthesis of DNA processing and also suppresses formation of RNA to a lesser extent [190]. Bacterial growth inhibition by 115 was dramatically increased by irradiation with visible (blue) or near-UV light, as was its cytotoxicity towards a human colon carcinoma cell line [191]. These observations support an intercalating and cross-linking mode of action similar to that of gilvocarcin V described above.…”

An Esr Study of the Visible Light Photochemistry of Gilvocarcin V

“…singlet oxygen. vinyl group has been consistently associated with the greatest biological activity, be it antimicrobial (Nakano et al, 1981;Balitz et al, 1981), prophage inducing (Elespuru and Gonda, 1984), or antitumor (Balitz et al, 1981;Morimoto et al, 1981). In the presence of UV or visible radiation, GV becomes a DNA damaging agent at low doses in both bacterial (Elespuru and Gonda, 1984;Misra et al, 1985) and mammalian cells (Greenstein et al, 1986). Radiation-dependent DNA strand breaking (Wei et al, 1982b;Tse-Dinh and McGee, 1987) and DNA interaction (Elespuru and Look, 1988) of GV with DNA in vitro have been observed.…”