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抗小鼠皮肤利什曼病的吲唑衍生物

Indazole Derivatives Against Murine Cutaneous Leishmaniasis.

作者信息

Mollineda-Diogo Niurka, Pérez-Castillo Yunierkis, Sifontes-Rodríguez Sergio, Marrero-Chang Osmani, Meneses-Marcel Alfredo, Escalona-Montaño Alma Reyna, Aguirre-García María Magdalena, Espinosa-Buitrago Teresa, Morales-Moreno Yeny, Arán-Redó Vicente

机构信息

Centro de Bioactivos Químicos, Universidad Central "Marta Abreu" de Las Villas, Santa Clara 54800, Villa Clara, Cuba.

Grupo de Bio-Quimioinformática and Facultad de Ingeniería y Ciencias Aplicadas, Universidad de Las Américas, Quito 170125, Ecuador.

出版信息

Pharmaceuticals (Basel). 2025 Jul 25;18(8):1107. doi: 10.3390/ph18081107.

Abstract

: Leishmaniasis is a zoonotic and anthropozoonotic disease with significant public health impact worldwide and is classified as a neglected tropical disease. The search for new affordable treatments, particularly oral and/or topical ones that are easy to administer and have fewer side effects, remains a priority for the scientific community in this field of research. In previous investigations, 3-alkoxy-1-benzyl-5-nitroindazole derivatives showed remarkable in vitro results against species, and predictions of absorption, distribution, metabolism, excretion, and toxicity properties, as well as pharmacological scores, of the compounds classified as active were superior to those of amphotericin B, indicating their potential as candidates for in vivo studies. Therefore, the aim of the present study was to evaluate the in vivo antileishmanial activity of the indazole derivatives NV6 and NV16. : The compounds were administered intralesionally at concentrations of 10 and 5 mg/kg in a BALB/c mouse model of cutaneous leishmaniasis caused by . To evaluate the efficacy of the compounds, indicators such as lesion size, ulcer area, lesion weight, and parasitic load were determined. Amphotericin B was used as a positive control. : The compound NV6 showed leishmanicidal activity comparable to that observed with amphotericin B, with a significant reduction in lesion development and parasite load, while NV16 caused a reduction in ulcer area. : These results provide strong evidence for the antileishmanial activity of NV6 and support future studies to improve its pharmacokinetic profile, as well as the investigation of combination therapies with other chemotherapeutic agents currently in use.

摘要

利什曼病是一种人畜共患和人兽共患病,在全球范围内对公共卫生有重大影响,被归类为被忽视的热带病。寻找新的经济实惠的治疗方法,特别是易于给药且副作用较少的口服和/或局部治疗方法,仍然是该研究领域科学界的首要任务。在先前的研究中,3-烷氧基-1-苄基-5-硝基吲唑衍生物对 物种显示出显著的体外效果,对被归类为活性化合物的吸收、分布、代谢、排泄和毒性特性以及药理学评分的预测优于两性霉素B,表明它们作为体内研究候选物的潜力。因此,本研究的目的是评估吲唑衍生物NV6和NV16的体内抗利什曼活性。:在由 引起的皮肤利什曼病的BALB/c小鼠模型中,以10和5mg/kg的浓度进行皮损内给药。为了评估化合物的疗效,测定了病变大小、溃疡面积、病变重量和寄生虫负荷等指标。两性霉素B用作阳性对照。:化合物NV6显示出与两性霉素B相当的杀利什曼活性,病变发展和寄生虫负荷显著降低,而NV16导致溃疡面积减小。:这些结果为NV6的抗利什曼活性提供了有力证据,并支持未来改善其药代动力学特征的研究,以及与目前使用的其他化疗药物联合治疗的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0059/12389175/08640066b09d/pharmaceuticals-18-01107-g001.jpg

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