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Molecules 2010, 15(10), 7378-7394; doi:10.3390/molecules15107378
Article

Synthesis, Gastroprotective Effect and Cytotoxicity of New Amino Acid Diterpene Monoamides and Diamides

1,* , 1, 2, 3, 4 and 2
Received: 9 August 2010; in revised form: 5 October 2010 / Accepted: 14 October 2010 / Published: 21 October 2010
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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.
Keywords: labdane diterpenes; amino acid ester amides; gastroprotective effect; cytotoxicity labdane diterpenes; amino acid ester amides; gastroprotective effect; cytotoxicity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Schmeda-Hirschmann, G.; Pertino, M.W.; Rodriguez, J.A.; Monsalve, F.; Droguett, D.; Theoduloz, C. Synthesis, Gastroprotective Effect and Cytotoxicity of New Amino Acid Diterpene Monoamides and Diamides. Molecules 2010, 15, 7378-7394.

AMA Style

Schmeda-Hirschmann G, Pertino MW, Rodriguez JA, Monsalve F, Droguett D, Theoduloz C. Synthesis, Gastroprotective Effect and Cytotoxicity of New Amino Acid Diterpene Monoamides and Diamides. Molecules. 2010; 15(10):7378-7394.

Chicago/Turabian Style

Schmeda-Hirschmann, Guillermo; Pertino, Mariano Walter; Rodriguez, Jaime A.; Monsalve, Francisco; Droguett, Daniel; Theoduloz, Cristina. 2010. "Synthesis, Gastroprotective Effect and Cytotoxicity of New Amino Acid Diterpene Monoamides and Diamides." Molecules 15, no. 10: 7378-7394.


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