Ascofuranone (AF)是一种从各种丝状真菌中分离出的新型萜类化合物，包括埃及青霉菌，被认为是一种有潜力的药物先导化合物，可用于治疗寄生虫和癌症。在本研究中，我们证明了AF及其衍生物是有效的驱虫剂，尤其对引起泡状棘球绦虫病的多房棘球绦虫具有特别的抗菌活性。我们测量了AF及其衍生物对多房棘球绦虫幼虫线粒体有氧和无氧呼吸系统的抑制活性。一些衍生物抑制了II类复合物（琥珀酸：醌还原酶[SQR]; IC50 = 0.037至0.135μM），也抑制了I到III类复合物（NADH：细胞色素c还原酶; IC50 = 0.008至0.401μM），但未抑制I类复合物（NADH：醌还原酶），表明线粒体复合物II和III为其作用靶点。特别地，无氧途径中复合物II的抑制尤为显著，因为多房棘球绦虫除了使用NADH氧化酶（氧呼吸）外，还使用NADH：富马酸还原酶（富马酸呼吸），导致氧化磷酸化的ATP合成完全关闭。富马酸残基复合物II的构效关系研究表明，AF的功能基团对抑制作用至关重要。AF衍生物与复合物II结合位点内氨基酸残基之间有可能发生疏水作用和氢键作用的结合方式预测。体外培养实验证明，AF衍生物在有氧和无氧条件下逐渐降低了原始下壳的存活能力。这些研究结果证实，在多房棘球绦虫中，AF及其衍生物是第一批富马酸呼吸和氧呼吸的双重抑制剂，并且是开发抗棘球绦虫药物的潜在先导化合物。

Ascofuranone (AF), a meroterpenoid isolated from various filamentous fungi, including Acremonium egyptiacum, has been reported as a potential lead candidate for drug development against parasites and cancer. In this study, we demonstrated that AF and its derivatives are potent anthelminthic agents, particularly against Echinococcus multilocularis, which is the causative agent of alveolar echinococcosis. We measured the inhibitory activities of AF and its derivatives on the mitochondrial aerobic and anaerobic respiratory systems of E. multilocularis larvae. Several derivatives inhibited complex II (succinate:quinone reductase [SQR]; IC50 = 0.037 to 0.135 μM) and also complex I to III (NADH:cytochrome c reductase; IC50 = 0.008 to 0.401 μM), but not complex I (NADH:quinone reductase), indicating that mitochondrial complexes II and III are the targets. In particular, complex II inhibition in the anaerobic pathway was notable because E. multilocularis employs NADH:fumarate reductase (fumarate respiration), in addition to NADH oxidase (oxygen respiration), resulting in complete shutdown of ATP synthesis by oxidative phosphorylation. A structure-activity relationship study of E. multilocularis complex II revealed that the functional groups of AF are essential for inhibition. Binding mode prediction of AF derivatives to complex II indicated potential hydrophobic and hydrogen bond interactions between AF derivatives and amino acid residues within the quinone binding site. Ex vivo culture assays revealed that AF derivatives progressively reduced the viability of protoscoleces under both aerobic and anaerobic conditions. These findings confirm that AF and its derivatives are the first dual inhibitors of fumarate and oxygen respiration in E. multilocularis and are potential lead compounds in the development of anti-echinococcal drugs.