Isern Jaime A, Carlucci Renzo, Labadie Guillermo R, Porta Exequiel O J
Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Rössle-Str. 10, 13125 Berlin, Germany.
Instituto de Química Rosario, Universidad Nacional de Rosario, CONICET, S2002LRK Rosario, Argentina.
Trop Med Infect Dis. 2025 May 20;10(5):142. doi: 10.3390/tropicalmed10050142.
Parasitic diseases represent a severe global burden, with current treatments often limited by toxicity, drug resistance, and suboptimal efficacy in chronic infections. This review examines the emerging role of triazole-based compounds, originally developed as antifungals, in advanced antiparasitic therapy. Their unique structural properties, particularly those of 1,2,3- and 1,2,4-triazole isomers, facilitate diverse binding interactions and favorable pharmacokinetics. By leveraging innovative synthetic approaches, such as click chemistry (copper-catalyzed azide-alkyne cycloaddition) and structure-based design, researchers have repurposed and optimized triazole scaffolds to target essential parasite pathways, including sterol biosynthesis via CYP51 and other novel enzymatic routes. Preclinical studies in models of Chagas disease, leishmaniasis, malaria, and helminth infections demonstrate that derivatives like posaconazole, ravuconazole, and DSM265 exhibit potent in vitro and in vivo activity, although their primarily static effects have limited their success as monotherapies in chronic cases. Combination strategies and hybrid molecules have demonstrated the potential to enhance efficacy and mitigate drug resistance. Despite challenges in achieving complete parasite clearance and managing potential toxicity, interdisciplinary efforts across medicinal chemistry, parasitology, and clinical research highlight the significant potential of triazoles as components of next-generation, patient-friendly antiparasitic regimens. These findings support the further optimization and clinical evaluation of triazole-based agents to improve treatments for neglected parasitic diseases.
寄生虫病是一项严峻的全球负担，当前的治疗方法常常受到毒性、耐药性以及在慢性感染中疗效欠佳的限制。本综述探讨了最初作为抗真菌药物开发的三唑类化合物在先进抗寄生虫治疗中的新作用。它们独特的结构特性，特别是1,2,3 - 和1,2,4 - 三唑异构体的结构特性，促进了多种结合相互作用和良好的药代动力学。通过利用创新的合成方法，如点击化学（铜催化的叠氮化物 - 炔烃环加成）和基于结构的设计，研究人员对三唑支架进行了重新利用和优化，以靶向寄生虫的关键途径，包括通过CYP51的甾醇生物合成和其他新的酶促途径。恰加斯病、利什曼病、疟疾和蠕虫感染模型的临床前研究表明，泊沙康唑、雷夫康唑和DSM265等衍生物在体外和体内均表现出强大的活性，尽管它们主要的静态作用限制了它们在慢性病单药治疗中的成功。联合策略和杂合分子已显示出增强疗效和减轻耐药性的潜力。尽管在实现完全清除寄生虫和管理潜在毒性方面存在挑战，但药物化学、寄生虫学和临床研究的跨学科努力突出了三唑类化合物作为下一代患者友好型抗寄生虫治疗方案组成部分的巨大潜力。这些发现支持对基于三唑的药物进行进一步优化和临床评估，以改善对被忽视寄生虫病的治疗。
