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Low level toxicity and antitumor activity of butyric mono- and polyester monosaccharide derivates in mice
P Pouillart1, G Ronco, I Cerutti
1Laboratoire de Chimie Organique et Cinétique, UFR des Sciences, Université de Picardie, Amiens, France.
Abstract:
This study compares the antitumor activity of five mono- and polyesters of n-butyric acid derived from monosaccharides in the murine model of Crocker 180 TG Sarcoma. Tumor incidence at ten days, mean survival time and final survival rate were significantly affected in all cases. Combined treatment by butyric esters, alpha/beta interferon (IFN) and/or Corynebacterium parvum used as immunestimulator improved the antitumor protection. Studies of acute toxicity in mice, performed by i.p. and oral routes, showed the low toxicity of butyric esters, which were devoid of detectable side effects with no incidence on ponderal growth when administered per os in rats daily for one month. Finally, a comparative study of antitumor activity, toxicity and water-solubility of various butyric esters enabled us to select among these new molecules two isomers (carbon-3 and carbon-6 of the glucose ring substituted with n-butyric acid) derived from monoacetone glucose for further investigations of their biological mechanism in vivo and in vitro.
Insights
This study investigated butyric acid esters derived from monosaccharides for antitumor activity against Crocker Sarcoma. These compounds demonstrated low toxicity and improved antitumor effects when combined with immunotherapy.
Area of Science:
- Biochemistry
- Pharmacology
- Oncology
Background:
- Monosaccharide-derived butyric acid esters are novel compounds with potential therapeutic applications.
- The Crocker 180 TG Sarcoma is a murine model used to evaluate antitumor agents.
Purpose of the Study:
- To compare the antitumor activity of five n-butyric acid esters derived from monosaccharides.
- To assess the acute toxicity and side effects of these esters.
- To identify promising candidates for further in vivo and in vitro investigation.
Main Methods:
- Antitumor activity was evaluated in the murine model of Crocker 180 TG Sarcoma.
- Tumor incidence, mean survival time, and survival rate were measured.
- Acute toxicity was assessed via intraperitoneal and oral routes in mice and rats.
- Water-solubility and comparative antitumor activity were analyzed.
Main Results:
- All tested butyric esters significantly affected tumor incidence, mean survival time, and survival rate.
- Combined treatment with butyric esters, interferon (IFN), and Corynebacterium parvum enhanced antitumor protection.
- Butyric esters exhibited low acute toxicity with no observable side effects or impact on growth in rats.
- Two specific isomers, derived from monoacetone glucose, were identified as promising candidates.
Conclusions:
- Monosaccharide-derived n-butyric acid esters show significant antitumor potential.
- These compounds possess a favorable toxicity profile, making them suitable for further research.
- Combination therapy with immunotherapy agents can potentiate antitumor effects.
- Specific isomers warrant further investigation for their therapeutic mechanisms.