对泽尔科瓦米辛类似物的合成和抗癌活性评估
Xinrong Xie1, Hongshun Huang1, Yogini S Jaiswal2
1Key Laboratory of Chemistry and Engineering of Forest Products (State Ethnic Affairs Commission), Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning 530006, China.
Molecules (Basel, Switzerland)
|September 28, 2024
概括
研究人员合成了新型泽尔科瓦米辛类似物,即具有潜在生物活性的循环八. 合成的类似物体在体外没有显示出对Huh-7细胞的显著抗癌活性.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 类化学 类化学
背景情况:
- 泽尔科瓦米辛家族包括以强大的抗菌和抗病毒特性而闻名的循环八.
- 它们独特的结构和生物活性使它们成为合成化学家的有吸引力的目标.
- 之前的合成努力仅限于泽尔科瓦米辛和泽尔科瓦米辛G.
研究的目的:
- 为了合成新型泽尔科瓦米辛类似物.
- 为了评估这些类似物体的体外抗癌活性.
- 为了探索在访问特定的zelkovamycin结构中所面临的合成挑战.
主要方法:
- 使用Fmoc固相合成来构建线性前体.
- 在高稀释条件下的循环化被用来形成循环八.
- 核磁共振 (NMR) 分析被用于结构阐明.
- 在实验室中对Huh-7细胞进行了抗癌活性评估.
主要成果:
- 化合物21是一种泽尔科瓦米辛类似物,经过合成和表征,但被确定不是天然的泽尔科瓦米辛H.
- 在合成过程中,D-Abu残留物对L-Abu的表皮化被确定为一个关键挑战,导致一种中介物 (20),阻碍了泽尔科瓦米辛H合成.
- 通过修改氨基酸残留物来合成类型22和23.
- 合成的类似物21-23表现出较弱的抗癌活性,IC50值大于50μM对Huh-7细胞.
结论:
- 该研究成功合成了新型泽尔科瓦米辛类似物,扩大了这些循环八的库.
- 一个涉及氨基酸表皮化合成挑战被确定和描述.
- 合成的类似物在体外对测试细胞系的抗癌疗效有限.
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