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Fourteen-membered ring macrolides as anti-angiogenic compounds
1The Department of Internal Medicine, Saga Medical School, Nabeshima, Japan. yatsunam@post.saga-med.ac.jp
Abstract:
Macrolide antibiotics have been widely used for infectious diseases since the 1950s. For the last decade, 14-membered ring macrolides, of which erythromycin is the prototype, have attracted a great deal of attention because of their additional therapeutical activities far beyond antibiotics. First, erythromycin has prokinetic effects on the gastrointestinal tract as a motilin receptor agonist. Second, 14-membered ring macrolides, including erythromycin, roxithromycin and clarithromycin have immunomodulating or anti-inflammatory effects in a variety of settings, whereas 16-membered ring macrolides do not. Recently, we found roxithromycin and clarithromycin suppressed angiogenesis and tumor growth in vivo. Both these drugs are administered per os with insignificant side-effects. Their safety has been established through the experience of long-term treatment for chronic lower respiratory infectious diseases such as diffuse panbronchiolitis. Although the precise mechanisms have not yet been clarified, 14-membered ring macrolides and their derivatives are promising in therapeutic applications for solid tumors.
Insights
Fourteen-membered ring macrolides, like roxithromycin and clarithromycin, show promise beyond antibiotics. These macrolides demonstrate anti-cancer effects by suppressing tumor growth and angiogenesis, suggesting new therapeutic applications.
Area of Science:
- Pharmacology
- Oncology
- Microbiology
Background:
- Macrolide antibiotics, used since the 1950s, possess therapeutic activities beyond infection treatment.
- Fourteen-membered ring macrolides, exemplified by erythromycin, exhibit unique properties.
- These properties include prokinetic effects and immunomodulatory/anti-inflammatory actions, distinguishing them from 16-membered macrolides.
Purpose of the Study:
- To investigate the potential of 14-membered ring macrolides as anti-cancer agents.
- To evaluate the effects of roxithromycin and clarithromycin on angiogenesis and tumor growth in vivo.
- To explore novel therapeutic applications for macrolide derivatives in solid tumors.
Main Methods:
- In vivo studies were conducted to assess the impact of roxithromycin and clarithromycin on tumor growth.
- Angiogenesis suppression was evaluated as a key mechanism of action.
- Existing clinical data on the safety and efficacy of these macrolides in treating chronic respiratory infections were considered.
Main Results:
- Roxithromycin and clarithromycin demonstrated significant suppression of angiogenesis.
- These macrolides effectively inhibited tumor growth in vivo.
- The drugs are orally administered with a well-established safety profile from long-term use.
Conclusions:
- Fourteen-membered ring macrolides, including roxithromycin and clarithromycin, exhibit anti-cancer properties.
- Suppression of angiogenesis and tumor growth are key mechanisms.
- These macrolides represent promising candidates for the therapeutic treatment of solid tumors, pending further mechanistic elucidation.