3-烷氧基-1-苄基-5-硝基吲唑衍生物是有效的抗利什曼原虫化合物。
3-Alkoxy-1-Benzyl-5-Nitroindazole Derivatives Are Potent Antileishmanial Compounds.
机构信息
Centro de Bioactivos Químicos, Universidad Central "Marta Abreu" de Las Villas, Santa Clara, Villa Clara 250512, Cuba.
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México-Consejo Nacional de Humanidades, Ciencias y Tecnologías (CONAHCYT), Ciudad de México 14080, Mexico.
出版信息
Int J Mol Sci. 2024 Oct 1;25(19):10582. doi: 10.3390/ijms251910582.
Indazoles have previously been identified as molecules with antiprotozoal activity. In this study, we evaluate the in vitro activity of thirteen 3-alkoxy-1-benzyl-5-nitroindazole derivatives (series D) against , and . In vitro, cytotoxicity against mouse peritoneal macrophages and growth inhibitory activity in promastigotes were evaluated for all compounds, and those showing adequate activity and selectivity were tested against intracellular amastigotes. Transmission and scanning electron microscopy were employed to study the effects of 3-alkoxy-1-benzyl-5-nitroindazole and 2-benzyl-5-nitroindazolin-3-one derivatives on promastigotes of . Compounds NV6 and NV8 were active in the two life stages of the three species, with the latter showing the best indicators of activity and selectivity. 3-alkoxy-1-benzyl-5-nitroindazole derivatives (series D) showed in vitro activity comparable to that of amphotericin B against the promastigote stage of spp. Two compounds were also found to be active the amastigote stage. Electron microscopy studies confirmed the antileishmanial activity of the indazole derivatives studied and support future research on this family of compounds as antileishmanial agents.
先前已鉴定出吲唑类化合物具有抗原生动物活性。在这项研究中,我们评估了 13 种 3-烷氧基-1-苄基-5-硝基吲唑衍生物(D 系列)对 、 和 的体外活性。对所有化合物进行了体外对小鼠腹腔巨噬细胞的细胞毒性和对前鞭毛体的生长抑制活性评价,对显示出足够活性和选择性的化合物进行了针对细胞内无鞭毛体的测试。透射和扫描电子显微镜用于研究 3-烷氧基-1-苄基-5-硝基吲唑和 2-苄基-5-硝基吲唑啉-3-酮衍生物对 的前鞭毛体的影响。化合物 NV6 和 NV8 在三种生物的两个生活阶段均具有活性,后者表现出最佳的活性和选择性指标。3-烷氧基-1-苄基-5-硝基吲唑衍生物(D 系列)对 spp. 的前鞭毛体阶段显示出与两性霉素 B 相当的体外活性。两种化合物也被发现对无鞭毛体阶段具有活性。电子显微镜研究证实了所研究的吲唑衍生物的抗利什曼原虫活性,并支持对该类化合物作为抗利什曼原虫药物的进一步研究。