Laboratorio de Zoonosis Parasitarias, Instituto de Investigaciones en Producción, Sanidad y Ambiente (IIPROSAM), Facultad de Ciencias Exactas y Naturales (FCEyN), Universidad Nacional de Mar del Plata (UNMdP), Mar del Plata, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Instituto Académico Pedagógico de Ciencias Básicas y Aplicadas, Universidad Nacional de Villa María, Villa María, Córdoba, Argentina.
Acta Trop. 2020 May;205:105411. doi: 10.1016/j.actatropica.2020.105411. Epub 2020 Feb 23.
Alveolar echinococcosis is one of the most dangerous parasitic zoonoses. This disease, widely distributed in the northern hemisphere, is caused by the metacestode stage of the tapeworm Echinococcus multilocularis. All surgical and non-surgical patients should perform chemotherapy with benzimidazoles, mainly with albendazole. However, the efficacy of albendazole is variable due to its deficient pharmacokinetic properties. Therefore, the need to find new therapeutic alternatives for the treatment of alveolar echinococcosis is evident. Menthol is a natural compound of low toxicity, used in industries such as cosmetics and gastronomy and generally recognized as safe by the Food and Drug Administration. In addition, menthol has important pharmacological effects and is effective against a wide variety of organisms. The development of prodrugs allows improving the pharmacokinetic properties of the parental drug. To improve lipophilicity and therefore the bioavailability of menthol, a novel prodrug called menthol-pentanol was developed by masking the functional polar group of menthol by linking n-pentanol by a carbonate bond. The aim of the current work was to evaluate the in vitro and in vivo efficacy of menthol and menthol-pentanol against E. multilocularis. Menthol-pentanol had a greater protoscolicidal effect than menthol. In addition, the prodrug demonstrated a similar clinical efficacy to albendazole. The increase in lipophilicity of the prodrug with respect to menthol was reflected in an increase in its antiparasitic activity against E. multilocularis. Thus, menthol-pentanol appears as a promising candidate for further evaluation as a potential alternative for the treatment of alveolar echinococcosis.
泡型包虫病是最危险的寄生虫病之一。这种疾病广泛分布于北半球,是由带绦虫多房棘球蚴的囊尾蚴阶段引起的。所有手术和非手术患者都应使用苯并咪唑类药物进行化疗,主要是阿苯达唑。然而,由于其药代动力学特性不足,阿苯达唑的疗效存在差异。因此,显然需要寻找新的治疗替代方法来治疗泡型包虫病。薄荷醇是一种低毒性的天然化合物,用于化妆品和美食等行业,并且通常被食品和药物管理局认为是安全的。此外,薄荷醇具有重要的药理作用,对各种生物体都有效。前药的开发可以改善母体药物的药代动力学特性。为了提高薄荷醇的亲脂性,从而提高其生物利用度,通过用碳酸酯键将正戊醇连接到薄荷醇的功能极性基团上来开发一种新的前药薄荷醇-戊醇。目前这项工作的目的是评估薄荷醇和薄荷醇-戊醇对多房棘球蚴的体外和体内疗效。薄荷醇-戊醇比薄荷醇具有更大的原头蚴杀伤作用。此外,该前药表现出与阿苯达唑相似的临床疗效。前药相对于薄荷醇的亲脂性增加反映在其对多房棘球蚴的抗寄生虫活性增加。因此,薄荷醇-戊醇似乎是作为治疗泡型包虫病的潜在替代药物进一步评估的有前途的候选药物。
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