Liu Xuelian, Liu Huihui, Yin Fahong, Li Yiyi, Jiang Jiazhen, Xiao Yumei, Wu Yanhua, Qin Zhaohai
College of Science, China Agricultural University, Beijing 100193, China.
School of Pharmaceutical Sciences and Institute of Materia Medica, Xinjiang University, Urumqi 830017, China.
J Fungi (Basel). 2024 Jun 27;10(7):450. doi: 10.3390/jof10070450.
The triphenylphosphonium (TPP) cation has been widely used as a carrier for mitochondria-targeting molecules. We synthesized two commonly employed targeting systems, namely, ω-triphenylphosphonium fatty acids (group 2) and ω-triphenylphosphonium fatty alcohols (group 3), to assess the impact of the TPP module on the biological efficacy of mitochondria-targeting molecules. We evaluated their fungicidal activities against nine plant pathogenic fungi in comparison to alkyl-1-triphenylphosphonium compounds (group 1). All three compound groups exhibited fungicidal activity and displayed a distinct "cut-off effect", which depended on the length of the carbon chain. Specifically, group compounds showed a cut-off point at C (compound -), while group and compounds exhibited cut-off points at C (compound -) and C (compound -), respectively. Notably, group compounds displayed significantly higher fungicidal activity compared to groups and 3. However, group and compounds showed similar activity to each other, although susceptibility may depend on the pathogen tested. Initial investigations into the mechanism of action of the most active compounds suggested that their fungicidal performance may be primarily attributed to their ability to damage the membrane, as well as uncoupling activity and inhibition of fungal respiration. Our findings suggest that the TPP module used in delivery systems as aliphatic acyl or alkoxyl derivatives with carbon chains length < 10 will contribute negligible fungicidal activity to the TPP-conjugate compared to the effect of high level of accumulation in mitochondria due to its mitochondria-targeting ability. These results provide a foundation for utilizing TPP as a promising carrier in the design and development of more effective mitochondria-targeting drugs or pesticides.
三苯基鏻（TPP）阳离子已被广泛用作线粒体靶向分子的载体。我们合成了两种常用的靶向系统，即ω-三苯基鏻脂肪酸（第2组）和ω-三苯基鏻脂肪醇（第3组），以评估TPP模块对线粒体靶向分子生物学功效的影响。与烷基-1-三苯基鏻化合物（第1组）相比，我们评估了它们对九种植物病原真菌的杀菌活性。所有三个化合物组均表现出杀菌活性，并呈现出明显的“截止效应”，这取决于碳链的长度。具体而言，第1组化合物在C（化合物-）处显示出截止点，而第2组和第3组化合物分别在C（化合物-）和C（化合物-）处表现出截止点。值得注意的是，第1组化合物相比第2组和第3组显示出显著更高的杀菌活性。然而，第2组和第3组化合物彼此显示出相似的活性，尽管敏感性可能取决于所测试的病原体。对最具活性化合物作用机制的初步研究表明，它们的杀菌性能可能主要归因于其破坏膜的能力以及解偶联活性和对真菌呼吸的抑制作用。我们的研究结果表明，在递送系统中用作碳链长度<10的脂肪酰基或烷氧基衍生物的TPP模块，与其由于线粒体靶向能力而在线粒体中高水平积累的影响相比，对TPP缀合物的杀菌活性贡献可忽略不计。这些结果为在设计和开发更有效的线粒体靶向药物或农药中利用TPP作为有前景的载体提供了基础。
