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Thymol and eugenol derivatives as potential antileishmanial agents
Journal article   Peer reviewed

Thymol and eugenol derivatives as potential antileishmanial agents

Selene Maia de Morais, Nadja Soares Vila-Nova, Claudia Maria Leal Bevilaqua, Fernanda Cristina Rondon, Carlos Henrique Lobo, Arlindo de Alencar Araripe Noronha Moura, Antônia Débora Sales, Ana Paula Ribeiro Rodrigues, José Ricardo de Figuereido, Claudio Cabral Campello, …
Bioorganic & medicinal chemistry, Vol.22(21), pp.6250-6255
11/01/2014
DOI: 10.1016/j.bmc.2014.08.020
PMCID: PMC5106290
PMID: 25281268

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Abstract

Thymol and eugenol derivatives as anti-leishmanial agents 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 100mg/kg/day for 30days. The thymol derivatives demonstrated the greater activity than the eugenol derivatives, and benzoyl-thymol was the best inhibitor (8.67±0.28μg/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.
Thymol Eugenol Leishmania infatum chagasi

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