作为新型抗血栓剂的结构多样化的fusicoccane类型diterpenoids的高效采矿及其对血小板抑制的不同机制
Alan Bao1, Xue Gong1, Shuang Lin1,2
1Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Journal of medicinal chemistry
|January 27, 2026
概括
研究人员在Trichoderma harzianum中发现了一个新的基因集群,产生了33个fusiococcane diterpenoids. 两种化合物通过抑制血小板激活而不会影响血静,显示出安全的抗血小板治疗的前景.
科学领域:
- 自然产品化学 自然产品化学
- 菌类学 菌类学是指菌类学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 富西科坎类型的二类是具有多种生物活动的自然产品的一类.
- 特里科德玛属因其生物控制特性而闻名,但以前没有与子二二类生物合成有关.
- 识别新型基因集群对于发现新的生物活性化合物至关重要.
研究的目的:
- 发现和描述来自Trichoderma harzianum的新型状类二类植物.
- 为了研究分离的化合物的抗血小板和抗血栓活性.
- 探索在血栓形成治疗中的潜在治疗应用.
主要方法:
- 挖掘Trichoderma harzianum的基因组,以识别Fusicoccane双类基因集群 (Thm).
- 在Aspergillus oryzae中的Thm集群的异质表达.
- 用染色学和光谱技术分离和阐明33个状类型的三角形体的结构.
- 确定涉及GPVI和ROCK1信号的抗血小板途径的机制研究.
主要成果:
- 在Trichoderma.com中发现了第一个5/8/5型状类二类基因群 (Thm).
- 隔离了33种化类型的二氧化,其中包括30种新化合物.
- 识别罕见的化-化物杂交物 (化合物1和2).
- 化合物6选择性地对抗GPVI通路,抑制Syk和PLCγ2酸化.
- 化合物31通过一种ROCK1依赖的途径表现出抗血小板作用,抑制细胞骨重组.
- 这两种化合物都表现出治疗性解离,防止血栓形成而不会损害血静.
结论:
- Thm基因集群代表了多种状类型二类生物的新型来源.
- 化合物6和31具有独特的抗血小板机制,具有安全抗血小板治疗的潜力.
- 这项研究为从真菌天然产品中发现药物的新途径打开了大门.
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