Abstract |
Following our studies on the gastroprotective effect and cytotoxicity of terpene derivatives, new amides were prepared from the diterpene 8(17)-labden-15,19-dioic acid ( junicedric acid) and its 8(9)-en isomer with C-protected amino acids ( amino acid esters). The new compounds were evaluated for their gastroprotective effect in the ethanol/HCl-induced gastric lesions model in mice, as well as for cytotoxicity using the following human cell lines: normal lung fibroblasts (MRC-5), gastric adenocarcinoma cells (AGS) and liver hepatocellular carcinoma (Hep G2). A dose-response experiment showed that at 25 mg/kg the C-15 leucyl and C-15,19-dileucylester amides of junicedric acid reduced gastric lesions by about 65.6 and 49.6%, respectively, with an effect comparable to lansoprazole at 20 mg/kg (79.3% lesion reduction). The comparison of the gastroprotective effect of 18 new amino acid ester amides was carried out at a single oral dose of 25 mg/kg. Several compounds presented a strong gastroprotective effect, reducing gastric lesions in the 70.9-87.8% range. The diprolyl derivative of junicedric acid, the most active product of this study (87.8% lesion reduction at 25 mg/kg) presented a cytotoxicity value comparable with that of the reference compound lansoprazole. The structure-activity relationships are discussed.
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Authors | Guillermo Schmeda-Hirschmann, Mariano Walter Pertino, Jaime A Rodriguez, Francisco Monsalve, Daniel Droguett, Cristina Theoduloz |
Journal | Molecules (Basel, Switzerland)
(Molecules)
Vol. 15
Issue 10
Pg. 7378-94
(Oct 21 2010)
ISSN: 1420-3049 [Electronic] Switzerland |
PMID | 20966879
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amino Acids
- Diterpene Alkaloids
- Diterpenes
- diterpene 8(17)-labden-15,19-dioic acid
- Diamide
- Ethanol
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Topics |
- Amino Acids
(chemical synthesis, chemistry, pharmacology, therapeutic use)
- Animals
- Cell Line
- Diamide
(chemical synthesis, chemistry, pharmacology, therapeutic use)
- Diterpene Alkaloids
- Diterpenes
(chemical synthesis, chemistry, pharmacology, therapeutic use)
- Ethanol
(pharmacology)
- Gastric Mucosa
(pathology)
- Humans
- Male
- Mice
- Molecular Structure
- Stomach Ulcer
(chemically induced, drug therapy, pathology)
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