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Tetroxanes as New Agents against Leishmania amazonensis
Author(s) -
Antolínez Isabel V.,
Barbosa Luiz C. A.,
Borgati Tatiane F.,
Baldaia Almodvar,
Ferreira Sebastião R.,
Almeida Raquel M.,
Fujiwara Ricardo T.
Publication year - 2020
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.202000142
Subject(s) - leishmaniasis , leishmania , amastigote , cytotoxicity , chemistry , parasite hosting , toxicity , pharmacology , in vitro , microbiology and biotechnology , biology , biochemistry , immunology , organic chemistry , world wide web , computer science
Leishmaniasis is a neglected disease, caused by a parasite of Leishmania genus and widespread in the tropical and subtropical areas of the world. Currents drugs are limited due to their toxicity and parasite resistance. Therefore, the discovery of new treatment, more effective and less toxic, is urgent. In this study, we report the synthesis of six gem ‐dihydroperoxides ( 2a – 2f ), with yields ranging from 10 % to 90 %, utilizing a new methodology. The dihydroperoxides were converted into ten tetroxanes ( 3a – 3j ), among which six ( 3b , 3c , 3d , 3g , 3h and 3j ) showed activity against intracellular amastigotes of Leishmania amazonensis . The cytotoxicity of all compounds was also evaluated against canine macrophages (DH82), human hepatoma (HepG2) and monkey renal cells (BGM). Most compounds were more active and less toxic than potassium antimonyl tartrate trihydrate, used as positive control. Amongst all tetroxanes, 3b (IC 50 =0.64 μ m ) was the most active, being more selective than positive control in relation to DH82, HepG2 and BGM cells. In summary, the results revealed a hit compound for the development of new drugs to treat leishmaniasis.