Thymol and eugenol derivatives as potential antileishmanial agents
Autor: | Cláudio Cabral Campello, Ana Paula Ribeiro Rodrigues, Heitor Franco de Andrade, Arlindo A. Moura, Fernanda Cristina Macedo Rondon, Claudia Maria Leal Bevilaqua, Selene Maia de Morais, Nadja S. Vila-Nova, A.D. Sales, Mary E. Wilson, José Ricardo de Figuereido, C.H. Lobo |
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Rok vydání: | 2014 |
Předmět: |
Male
Clinical Biochemistry Antiprotozoal Agents Pharmaceutical Science Pharmacology Biochemistry Article Cell Line chemistry.chemical_compound Mice In vivo Drug Discovery parasitic diseases Eugenol medicine Animals Humans Leishmania infantum Amastigote Molecular Biology Thymol Mice Inbred BALB C biology Macrophages Organic Chemistry biology.organism_classification medicine.disease Leishmania Visceral leishmaniasis chemistry Molecular Medicine Leishmaniasis Visceral Growth inhibition ANTI-INFECCIOSOS |
Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
ISSN: | 1464-3391 |
Popis: | In Northeastern Brazil visceral leishmaniasis is endemic with lethal cases among humans and dogs. Treatment is toxic and 5–10% of humans die despite treatment. The aim of this work was to survey natural active compounds to find new molecules with high activity and low toxicity against Leishmania infantum chagasi. The compounds thymol and eugenol were chosen to be starting compounds to synthesize acetyl and benzoyl derivatives and to test their antileishmanial activity in vitro and in vivo against L. i. chagasi. A screening assay using luciferase-expressing promastigotes was used to measure the growth inhibition of promastigotes, and an ELISA in situ was performed to evaluate the growth inhibition of amastigote. For the in vivo assay, thymol and eugenol derivatives were given IP to BALB/c mice at 100 mg/kg/day for 30 days. The thymol derivatives demonstrated the greater activity than the eugenol derivatives, and benzoyl- thymol was the best inhibitor (8.67 ± 0.28 μg/mL). All compounds demonstrated similar activity against amastigotes, and acetyl-thymol was more active than thymol and the positive control drug amphotericin B. Immunohistochemistry demonstrated the presence of Leishmania amastigote only in the spleen but not the liver of mice treated with acetyl-thymol. Thus, these synthesized derivatives demonstrated anti-leishmanial activity both in vitro and in vivo. These may constitute useful compounds to generate new agents for treatment of leishmaniasis. |
Databáze: | OpenAIRE |
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