The activities of wortmannilactones against helminth electron transport chain enzymes, structure-activity relationships, and the effect on Trichinella spiralis infected mice
| Autor: | Yi-xin Ren, Xuan Shi, Yan Xing, Yu Cui, Yuesheng Dong, Aiyu Hao, Wen-Cai Liu, Zhilong Xiu, Sun Yu, Xue-Qiang Zhang |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Oxidoreductases Acting on CH-CH Group Donors Dihydropyran Trichinella spiralis Trichinella Reductase Electron Transport Mice Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Drug Discovery Animals Moiety Structure–activity relationship Quinone Reductases Anthelmintics Pharmacology chemistry.chemical_classification biology Trichinellosis biology.organism_classification In vitro Mitochondria Disease Models Animal 030104 developmental biology Enzyme Electron Transport Chain Complex Proteins Biochemistry chemistry Macrolides Energy Metabolism |
| Zdroj: | The Journal of Antibiotics. 71:731-740 |
| ISSN: | 1881-1469 0021-8820 |
| DOI: | 10.1038/s41429-018-0061-z |
| Popis: | Biotransformation of wortmannilactone F (3) using the marine-derived fungus DL1103 generated wortmannilactone M (1), a novel analog of wortmannilactone, which was a reduction product of 3 at the C-3 carbonyl group. The in vitro inhibitory activities of 10 wortmannilactones, including 1, against electron transport enzymes indicated that all the wortmannilactones were selective inhibitors of NADH-fumarate reductase and NADH-rhodoquinone reductase. The structure-activity relationship analysis showed that the relative configuration of C1" and C5", the positions of double bonds, the oxygen atoms in the dihydropyran moiety, and the keto-carbonyl group in the oxabicyclo-[2.2.1]-heptane moiety were important to the inhibitory activity of wortmannilactones. In vivo studies indicated that 3 significantly decreased the number and size of adult worms in Trichinella spiralis-infected mice in a dose-dependent manner. Notable changes in the cuticle and microvilli of T. spiralis were also observed. Our data provided useful information in the research and development of polyketides with dihydropyran and oxabicyclo [2.2.1] heptane moieties as antihelminthics. |
| Databáze: | OpenAIRE |
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