合成海洋灵感的多面DNA破坏性螺旋氧indoles与NSCLC和相关的细菌感染作斗争
Mohammad Shahidul Islam1, Assem Barakat1, Abdul Majeed Abdullah Alayyaf1
1Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia.
ACS medicinal chemistry letters
|May 14, 2025
概括
海洋灵感的螺旋氧indoles显示对非小细胞肺癌 (NSCLC) 和黄金葡萄球菌的双重作用. 化合物4p表现出强大的抗癌和抗菌作用,破坏DNA并诱导亡.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 药理学 药理学是指药理学的学科.
背景情况:
- 针对性治疗对于非小细胞肺癌 (NSCLC) 和细菌感染至关重要.
- 海洋天然产品为药物发现提供了有希望的支架.
研究的目的:
- 设计和合成具有双重抗瘤和抗菌活性的新型海洋灵感的螺旋氧.
- 评估这些化合物对NSCLC和黄金葡萄球菌的疗效.
主要方法:
- 合成的立体选择性 [3 + 2] 循环添加.
- 细胞毒性和选择性的MTT测定.
- 抗菌活性最小抑制度 (MIC). 抗菌活性最小抑制度 (MIC).
- 化生物传感器用于DNA损伤评估.
- 分子对接和亡试验.
主要成果:
- 化合物4p对高瘤选择性 (SI = 58.28) 的NSCLC细胞表现出强烈的细胞毒性 (IC50 = 0.042 μM).
- 化合物4p显示抗黄金菌的抗菌活性 (MIC = 25μg/mL).
- 在小牛胸腺和金黄色细菌DNA中观察到DNA损伤.
- 细胞亡研究显示,G1/S阶段细胞周期停止和A549细胞的细胞亡增加.
结论:
- 化合物4p是开发针对NSCLC和黄金色杆菌感染的双重作用药物的有希望的主要候选物.
- 这项研究证实了海洋灵感的螺旋氧indoles在药物发现的潜力.
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