Triphenylphosphonium (TPP)-Conjugated Quinolone Analogs Displayed Significantly Enhanced Fungicidal Activity Superior to Its Parent Molecule
Although 1-hydroxy-4-quinolone derivatives, such as 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO), aurachin C, and floxacrine, have been reported as effective cytochrome <i>bc</i><sub>1</sub> complex inhibitors, the bioactivity of these products is not ideal, presumably due to t...
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/9/6/685 |
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| author | Jiayao Wang Xuelian Liu Fahong Yin Yanjun Xu Bin Fu Jiaqi Li Zhaohai Qin |
| author_facet | Jiayao Wang Xuelian Liu Fahong Yin Yanjun Xu Bin Fu Jiaqi Li Zhaohai Qin |
| author_sort | Jiayao Wang |
| collection | DOAJ |
| description | Although 1-hydroxy-4-quinolone derivatives, such as 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO), aurachin C, and floxacrine, have been reported as effective cytochrome <i>bc</i><sub>1</sub> complex inhibitors, the bioactivity of these products is not ideal, presumably due to their low bioavailability in tissues, particularly their poor solubility and low mitochondrial accumulation. In order to overcome the drawbacks of these compounds and develop their use as agricultural fungicides acting by cytochrome <i>bc</i><sub>1</sub> inhibition, in this study, three novel mitochondria-targeting quinolone analogs (mitoQNOs) were designed and synthesized by conjugating triphenylphosphonium (TPP) with quinolone. They exhibited greatly enhanced fungicidal activity compared to the parent molecule, especially mitoQNO<sub>11</sub>, which showed high antifungal activity against <i>Phytophthora capsici</i> and <i>Sclerotinia sclerotiorum</i> with EC<sub>50</sub> values of 7.42 and 4.43 μmol/L, respectively. In addition, mitoQNO<sub>11</sub> could inhibit the activity of the cytochrome <i>bc</i><sub>1</sub> complex of <i>P. capsici</i> in a dose-dependent manner and effectively depress its respiration and ATP production. The greatly decreased mitochondrial membrane potential and massively generated reactive oxygen species (ROS) strongly suggested that the inhibition of complex III led to the leakage of free electrons, which resulted in the damage of the pathogen cell structure. The results of this study indicated that TPP-conjugated QNOs might be used as agricultural fungicides by conjugating them with TPP. |
| first_indexed | 2024-03-11T02:16:01Z |
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| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-11T02:16:01Z |
| publishDate | 2023-06-01 |
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| series | Journal of Fungi |
| spelling | doaj.art-00dabd65c2f64172b456293435614ca22023-11-18T11:09:25ZengMDPI AGJournal of Fungi2309-608X2023-06-019668510.3390/jof9060685Triphenylphosphonium (TPP)-Conjugated Quinolone Analogs Displayed Significantly Enhanced Fungicidal Activity Superior to Its Parent MoleculeJiayao Wang0Xuelian Liu1Fahong Yin2Yanjun Xu3Bin Fu4Jiaqi Li5Zhaohai Qin6College of Science, China Agricultural University, Beijing 100193, ChinaPharmaceutical Institute, Xinjiang University, Urumqi 830046, ChinaCollege of Science, China Agricultural University, Beijing 100193, ChinaCollege of Science, China Agricultural University, Beijing 100193, ChinaCollege of Science, China Agricultural University, Beijing 100193, ChinaCollege of Science, China Agricultural University, Beijing 100193, ChinaCollege of Science, China Agricultural University, Beijing 100193, ChinaAlthough 1-hydroxy-4-quinolone derivatives, such as 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO), aurachin C, and floxacrine, have been reported as effective cytochrome <i>bc</i><sub>1</sub> complex inhibitors, the bioactivity of these products is not ideal, presumably due to their low bioavailability in tissues, particularly their poor solubility and low mitochondrial accumulation. In order to overcome the drawbacks of these compounds and develop their use as agricultural fungicides acting by cytochrome <i>bc</i><sub>1</sub> inhibition, in this study, three novel mitochondria-targeting quinolone analogs (mitoQNOs) were designed and synthesized by conjugating triphenylphosphonium (TPP) with quinolone. They exhibited greatly enhanced fungicidal activity compared to the parent molecule, especially mitoQNO<sub>11</sub>, which showed high antifungal activity against <i>Phytophthora capsici</i> and <i>Sclerotinia sclerotiorum</i> with EC<sub>50</sub> values of 7.42 and 4.43 μmol/L, respectively. In addition, mitoQNO<sub>11</sub> could inhibit the activity of the cytochrome <i>bc</i><sub>1</sub> complex of <i>P. capsici</i> in a dose-dependent manner and effectively depress its respiration and ATP production. The greatly decreased mitochondrial membrane potential and massively generated reactive oxygen species (ROS) strongly suggested that the inhibition of complex III led to the leakage of free electrons, which resulted in the damage of the pathogen cell structure. The results of this study indicated that TPP-conjugated QNOs might be used as agricultural fungicides by conjugating them with TPP.https://www.mdpi.com/2309-608X/9/6/685mitochondria-targetedquinolone analogsfungicidal activity |
| spellingShingle | Jiayao Wang Xuelian Liu Fahong Yin Yanjun Xu Bin Fu Jiaqi Li Zhaohai Qin Triphenylphosphonium (TPP)-Conjugated Quinolone Analogs Displayed Significantly Enhanced Fungicidal Activity Superior to Its Parent Molecule Journal of Fungi mitochondria-targeted quinolone analogs fungicidal activity |
| title | Triphenylphosphonium (TPP)-Conjugated Quinolone Analogs Displayed Significantly Enhanced Fungicidal Activity Superior to Its Parent Molecule |
| title_full | Triphenylphosphonium (TPP)-Conjugated Quinolone Analogs Displayed Significantly Enhanced Fungicidal Activity Superior to Its Parent Molecule |
| title_fullStr | Triphenylphosphonium (TPP)-Conjugated Quinolone Analogs Displayed Significantly Enhanced Fungicidal Activity Superior to Its Parent Molecule |
| title_full_unstemmed | Triphenylphosphonium (TPP)-Conjugated Quinolone Analogs Displayed Significantly Enhanced Fungicidal Activity Superior to Its Parent Molecule |
| title_short | Triphenylphosphonium (TPP)-Conjugated Quinolone Analogs Displayed Significantly Enhanced Fungicidal Activity Superior to Its Parent Molecule |
| title_sort | triphenylphosphonium tpp conjugated quinolone analogs displayed significantly enhanced fungicidal activity superior to its parent molecule |
| topic | mitochondria-targeted quinolone analogs fungicidal activity |
| url | https://www.mdpi.com/2309-608X/9/6/685 |
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