四种新的合成和抗癌机制 (II) 4'-替代-2,2':6',2''-特皮里丁复合物
Chun-Jie Liang1, Run-Chun Wu1, Xiao-Qiong Huang1
1Guangxi Key Lab of Agricultural Resources Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University, 1303 Jiaoyudong Road, Yulin 537000, PR China. qpqin2018@126.com.
Dalton transactions (Cambridge, England : 2003)
|January 8, 2024
概括
新 ((II) 抗癌药物选择性地向癌细胞中的线粒细胞衰变. 这些新型化合物对抗抗性卵巢癌具有很高的疗效,毒性最小,提供了一个有前途的新疗法策略.
科学领域:
- 药用化学 医学化学
- 癌症生物学 癌症生物学
- 线粒体生物学 线粒体生物学
背景情况:
- 线粒体,即功能失调的线粒体的选择性降解,是一个关键的细胞过程.
- 功能障碍的线粒体在癌症进展和耐药性方面发挥着作用.
- 基于的药物广泛用于癌症化疗,但可以表现出毒性和耐药性.
研究的目的:
- 设计和合成基于的新型化疗药物,具有菌细胞向性质.
- 评估这些化合物的抗瘤活性和作用机制,特别是对抗西斯胺耐药的癌细胞.
- 评估最有前途的化合物的治疗效率和毒性in vivo.
主要方法:
- 四个新型双核 (II) 复合物的合成和特征与4'-替代-2,2':6',2''-皮连接物.
- 选择性细胞毒性对抗抗西斯普拉丁 (SKO3cisR) 和敏感 (SKO3) 卵巢癌细胞和正常肝细胞的评估 (HL-7702).
- 调查线粒体细胞吸收途径的参与,包括线粒体膜潜力,水平,活性氧物种,线粒体DNA损伤,ATP水平和呼吸链功能.
- 在体内对化合物 (tpy1Pt) 的疗效和毒性研究.
主要成果:
- 合成的 (II) 复合物 (tpy1Pt-tpy4Pt) 与SKO3和HL-7702细胞相比,对SKO3cisR细胞表现出选择性细胞毒性.
- 发现Tpy1Pt和tpy2Pt通过线粒细胞衰变诱导癌细胞死亡,由被破坏的线粒细胞衰变蛋白质表达,线粒体功能障碍和改变的细胞能量证明.
- 双核化合物tpy1Pt表现出显著的治疗效率 (大约1. 52.4%) 在体内模型中具有微不足道的毒性.
结论:
- 新型 (II) 复合物有效地向细胞和表现出对抗抗西斯的卵巢癌细胞的选择性细胞毒性.
- 由于其强效和低毒性,Tpy1Pt代表了下一代双核 (II) 基抗癌药物候选人的前景.
- 向线粒菌提供了一个可行的策略,以克服抗在癌症治疗中.
相关概念视频
Targeted Cancer Therapies
7.6K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.6K
Electron Transport Chain: Complex I and II
13.4K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
13.4K
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
163
Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy. SP binds and activates...
163
Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists
292
Dopamine receptor antagonists, also known as antipsychotic agents, are critical in managing chemotherapy-induced vomiting. These antiemetic agents block dopamine receptors in the chemoreceptor trigger zone (CTZ), inhibiting signal transmission to the vomiting center. Antipsychotic agents encompass phenothiazines (PTZ), butyrophenones, benzamides, and thienobenzodiazepines (Zyprexa), which are utilized for their antiemetic and sedative properties.
Phenothiazines, such as prochlorperazine...
Phenothiazines, such as prochlorperazine...
292
Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists
205
5-HT3 receptor antagonists, such as dolasetron, granisetron (Kytril), ondansetron (Zofran), and palonosetron (Axoli), are crucial in managing chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea. These drugs selectively block 5-HT3 receptors in the visceral vagal and spinal afferent nerves, chemoreceptor trigger zone, and the vomiting center. They have a rapid onset of action and can be given as a single dose before chemotherapy. Ondansetron and granisetron, in particular,...
205


