Morita-Baylis-Hillman adduct shows in vitro activity against Leishmania (Viannia) braziliensis associated with a reduction in IL-6 and IL-10 but independent of nitric oxide.
Current treatments for different clinical forms of leishmaniasis are unsatisfactory, highly toxic and associated with increasing failure rates resulting from the emergence of resistant parasites. Leishmania (Viannia) braziliensis is the main aetiological agent of different clinical forms of American tegumentary leishmaniasis, including the mucosal form for which treatment has high failure rates. The aim of this work was to investigate the activity of the Morita-Baylis-Hillman adduct, methyl 2-{2-[hydroxy(2-nitrophenyl)methyl])acryloyloxy} benzoate in vitro against isolates of L. (V.) braziliensis obtained from patients with different clinical manifestations of tegumentary leishmaniasis: localized cutaneous leishmaniasis, mucosal leishmaniasis and disseminated cutaneous leishmaniasis. The adduct effectively inhibited the growth of promastigotes of the different isolates of L. (V.) braziliensis (IC(50) ≤ 7·77 μg/ml), as well as reduced the infection rate of macrophages infected with these parasites (EC(50) ≤ 1·37 μg/ml). It is remarkable to state that the adduct was more effective against intracellular amastigotes (P ≤ 0·0045). The anti-amastigote activity correlated with an immunomodulatory effect, since the adduct was able to decrease the production of IL-6 and IL-10 by the infected macrophages. However, its effect was independent of nitric oxide production. This work demonstrates the anti-leishmanial activity of methyl 2-{2-[hydroxy(2-nitrophenyl)methyl])acryloyloxy} benzoate and suggests its potential in the treatment of human infections caused by L. (V.) braziliensis.
Universidade Federal da Paraíba, Centro de Ciências Exatas e da Natureza, Programa de Pós-Graduação em Biologia Celular e Molecular, João Pessoa, Paraíba, Brazil.
F M
FM
Amorim
Y K S
YK
Rodrigues
T P
TP
Barbosa
P L N
PL
Néris
J P A
JP
Caldas
S C O
SC
Sousa
J A
JA
Leite
S
S
Rodrigues-Mascarenhas
M L A A
ML
Vasconcellos
M R
MR
Oliveira
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D007892:Leishmania braziliensis / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000981:Antiprotozoal Agents; D001565:Benzoates; D007155:Immunologic Factors; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C579295:methyl 2-(2-(hydroxy(2-nitrophenyl)methyl)acryloyloxy)benzoate; D016753:Interleukin-10; D009569:Nitric Oxide; C044605:methyl benzoate