甲酸介导的醇类化合物的环分裂导致重新设计的抗等离子体剂
Daniel C Schultz1, Alejandra Chávez-Riveros1, Michael G Goertzen1
1Department of Medicinal Chemistry, Center for Natural Product Drug Discovery & Development (CNPD3), College of Pharmacy, University of Florida, Gainesville, Florida 32610, USA. rhuigens@cop.ufl.edu.
Organic & biomolecular chemistry
|August 8, 2024
概括
天然产品的环状扭曲产生了47种来自印类化物的新分子. 一种保留素衍生物显示出对疟疾寄生虫有前途的抗质性活性.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 化学生物学 化学生物学
背景情况:
- 自然产品环扭曲策略为生物探索提供了复杂分子的访问.
- 印度醇化物是独特的化学支架的丰富来源.
- 迫切需要新的抗疟疾药物来对抗耐药疟疾.
研究的目的:
- 开发一个环分裂的策略,以印醇化物合成新型的小分子.
- 探索这些新化合物的化学空间和生物活动.
- 为了确定治疗疟疾的潜在候选药物.
主要方法:
- 在约欣宾,阿波文卡明,文伯宁和储上使用环分裂策略.
- 与甲酸盐和酒精/硫醇核友素反应的类化合物.
- 合成了47种新的小分子,并选它们的抗等离子体活性.
主要成果:
- 合成了47种新的小分子,根据起始类化合物,具有不同的二重选择性.
- 氨酸衍生品41显示出显著的抗菌活性 (EC50 = 0.50μM) 针对菌.
- 计算的自由能量计算解释了观察到的二极体选择性.
结论:
- 印类类化合物的环扭曲是一种有效的策略,用于生成多样化的化合物库.
- 新的衍生品可以具有重新设计的生物活动,例如抗等离子体效应.
- 这种方法为发现疟疾等人类疾病的新疗法提供了潜力.
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