PDF(Pubmed)
Abstract：
Human mycoses cover a diverse field of fungal diseases from skin disorders to systemic invasive infections and pose an increasing global health problem based on ineffective treatment options, the hampered development of new efficient drugs, and the emergence of resistant fungal strains. Niclosamide is currently applied for the treatment of worm infections. Its mechanisms of action, which include the suppression of mitochondrial oxidative phosphorylation (also known as mitochondrial uncoupling), among others, has led to a repurposing of this promising anthelmintic drug for the therapy of further human diseases such as cancer, diabetes, and microbial infections. Given the urgent need to develop new drugs against fungal infections, the considerable antifungal properties of niclosamide are highlighted in this review. Its chemical and pharmacological properties relevant for drug development are also briefly mentioned, and the described mitochondria-targeting mechanisms of action add to the current arsenal of approved antifungal drugs. In addition, the activities of further salicylanilide-based niclosamide analogs against fungal pathogens, including agents applied in veterinary medicine for many years, are described and discussed for their feasibility as new antifungals for humans. Preliminary structure-activity relationships are determined and discussed. Various salicylanilide derivatives with antifungal activities showed increased oral bioavailabilities when compared with niclosamide. The simple synthesis of salicylanilide-based drugs also vouchsafes a broad and cost-effective availability for poorer patient groups. Pertinent literature is covered until 2024.
摘要：
人类真菌病涵盖了从皮肤疾病到全身侵袭性感染的多种真菌疾病领域，并且基于无效的治疗选择，造成了越来越多的全球健康问题。阻碍了新的有效药物的开发，以及耐药真菌菌株的出现。氯硝柳胺目前用于治疗蠕虫感染。其作用机制,其中包括抑制线粒体氧化磷酸化（也称为线粒体解偶联），其中,导致了这种有前途的驱虫药的用途，用于治疗其他人类疾病，如癌症，糖尿病,和微生物感染。鉴于迫切需要开发针对真菌感染的新药，在这篇综述中强调了氯硝柳胺的抗真菌特性。还简要提到了与药物开发相关的化学和药理特性，所描述的线粒体靶向作用机制增加了目前批准的抗真菌药物库。此外,进一步的基于水杨酸苯胺的氯硝柳胺类似物对真菌病原体的活性，包括应用于兽医学多年的药物，描述和讨论了它们作为人类新抗真菌药的可行性。确定并讨论了初步的结构-活性关系。与氯硝柳胺相比，具有抗真菌活性的各种水杨酸酰苯胺衍生物显示出增加的口服生物利用度。基于水杨酰苯胺的药物的简单合成也为贫困患者群体提供了广泛且具有成本效益的可用性。相关文献一直覆盖到2024年。
