Synthesis of lupeol derivatives and their antileishmanial and antitrypanosomal activities |
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Authors: | Vanessa R Machado Louis P Sandjo Giovanni L Pinheiro Milene H Moraes Mario Steindel Moacir G Pizzolatti |
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Institution: | 1. Department of Pharmaceutical Sciences, Federal University of Santa Catarina (UFSC), Florianópolis, Santa Catarina, Brazil;2. Department of Chemistry, Federal University of Santa Catarina (UFSC), Florianópolis, Santa Catarina, Brazil;3. Department of Microbiology, Immunology and Parasitology, Federal University of Santa Catarina (UFSC), Florianópolis, Santa Catarina, Brazil |
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Abstract: | The natural product lupeol 1 was isolated from aerial parts of Vernonia scorpioides with satisfactory yield, which made it viable to be used as starting material in semisynthetic approach. Ten lupeol derivatives 2–11 were prepared by classical procedures. Including, five new esters derivatives 7–11, which were obtained by structural modifications in the isopropylidene fragment. All semisynthetic compounds and lupeol 1–11 were confirmed by 1H NMR, 13C NMR and HRMS. Their antiprotozoal activity was evaluated in vitro against L. amazonensis and T. cruzi. Derivative 6 showed the best antitrypanosomal activity (IC50 = 12.48 μg/mL) and the lowest cytotoxic derivative (CC50 = 161.50 μg/mL). The mechanism of action of the most active derivatives (4, 6 and 11) is not dependent from the enzyme trypanothione reductase. |
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Keywords: | Antileishmanial antitrypanosomal lupeol lupeol esters derivatives semisynthesis |
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