绿色合成和亚利法性N替代型甘氨酸衍生物的生物活性
Ameneh Jafari1, Mahboube Eslami Moghadam1, Hassan Mansouri-Torshizi2
1Chemistry and Chemical Engineering Research Center of Iran, Tehran, Iran.
ACS omega
|August 28, 2023
概括
这项研究介绍了通过绿色化学合成的新型N替代甘氨酸衍生物. 奥克提尔和2-氨基乙基氨基酸在细胞透和DNA相互作用方面表现出有前途的脂性,具有显著的毒性概况.
科学领域:
- 有机化学 有机化学
- 生物化学 生物化学
- 计算化学的计算化学
背景情况:
- 标准的氨基酸具有不对称的α-碳原子,甘氨酸是最简单的例外.
- 自然氨基酸是糖氨酸的C替代衍生物.
- 这项研究的重点是合成和表征新型N替代甘氨酸衍生物.
研究的目的:
- 设计和合成具有不同R组的新型N替代甘氨酸衍生物.
- 用光谱和计算方法来描述这些衍生品.
- 评估它们对生物-宏分子相互作用和毒性的潜力.
主要方法:
- 用N替代的甘氨酸衍生物的绿色合成.
- 使用点,FT-IR,质谱学,1H NMR和13C NMR进行表征.
- 密度功能理论 (DFT) 研究,ADME分析,生物可用性雷达,吸收光谱学,循环二元化,分子对接,粘度测量和光发射.
- 在体外对人类前皮纤维细胞 (HFF) 细胞系进行毒性测试.
主要成果:
- 合成的N替代型甘氨酸衍生物具有多种R组 (propyl到octyl).
- DFT研究确定了2-aminoheptyl glycine作为一种潜在的双酸联体.
- 奥克提尔和2-氨基乙基氨酸表现出高脂友性,这表明细胞透性很好.
- 和2-氨基乙基氨酸与DNA和人血清白蛋白 (HSA) 显著相互作用.
- 分子对接表明基和2-氨基基甘氨酸与DNA的强烈相互作用倾向.
- 结合DNA的研究证实了沟结合机制.
- 合成的衍生品对HFF细胞显示IC50值在127-344μM之间,其中2-aminoheptyl glycine是最有毒的.
结论:
- 成功合成和表征了N替代的甘氨酸衍生物.
- 由于有利的脂友性和DNA相互作用,octil和2-aminoheptyl glycine显示出作为候选药物的潜力.
- 需要进一步的研究来探索它们的治疗应用,并优化它们的特性.
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