Universidade Federal da Paraíba, Centro de Ciências Exatas e da Natureza, Programa de Pós-Graduação em Biologia Celular e Molecular, João Pessoa, Paraíba, Brazil.
Parasitology. 2013 Jan;140(1):29-38. doi: 10.1017/S0031182012001291. Epub 2012 Aug 20.
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.
目前针对不同临床形式利什曼病的治疗方法并不令人满意，这些方法具有高度毒性，并因寄生虫耐药性的出现而导致失败率不断增加。巴西利什曼原虫（Viannia）是不同临床形式美洲皮肤利什曼病的主要病原体，包括黏膜型，其治疗失败率很高。本工作旨在研究 Morita-Baylis-Hillman 加成物，即甲基 2-{2-[羟基（2-硝基苯基）甲基]丙烯酰氧基}苯甲酸酯对来自不同皮肤利什曼病临床表现的患者分离株的体外活性：局限性皮肤利什曼病、黏膜型皮肤利什曼病和播散性皮肤利什曼病。该加成物有效抑制了不同巴西利什曼原虫分离株的前鞭毛体生长（IC50≤7.77μg/ml），并降低了感染这些寄生虫的巨噬细胞的感染率（EC50≤1.37μg/ml）。值得注意的是，该加成物对细胞内无鞭毛体更有效（P≤0.0045）。抗无鞭毛体活性与免疫调节作用相关，因为该加成物能够降低感染巨噬细胞中 IL-6 和 IL-10 的产生。然而，其作用独立于一氧化氮的产生。本工作证明了甲基 2-{2-[羟基（2-硝基苯基）甲基]丙烯酰氧基}苯甲酸酯的抗利什曼原虫活性，并表明其在治疗由巴西利什曼原虫引起的人类感染方面具有潜力。
