发现水溶性英达衍生物作为强大的微管聚合抑制剂
Ying-Jie Cui1, Yi Zhou1, Xi-Wu Zhang1
1Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250012, China.
European journal of medicinal chemistry
|October 27, 2023
概括
新的因达衍生物显示出强大的抗癌活性. 化合物8l通过准布林聚合,有效地抑制癌细胞生长和瘤进展,为癌症治疗提供了一个有前途的新药物.
科学领域:
- 药用化学 医学化学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 印达衍生物正在研究抗癌性质.
- 化合物1最初表现有希望,但需要提高溶解度.
- 结构修改集中在1和6位的因达核心上.
研究的目的:
- 设计和合成具有增强水溶性和强大的抗癌活性的新型因达衍生物.
- 评估这些衍生品对各种癌症细胞系的疗效,包括耐药变异.
- 阐明作用机制,并评估体内疗效和毒性.
主要方法:
- 印达核的系统结构修改.
- 在体外对抗A549,Huh-7和T24癌细胞的抗增殖活性进行了评估.
- 评估氨酸聚合抑制,细胞循环停止和亡诱导.
- 在体内研究以评估瘤生长抑制和毒性.
主要成果:
- 伊达衍生物8l和8m在对测试的癌细胞系,包括对Taxol耐药的A549/Tax细胞,表现出高强度 (低纳米范围).
- 化合物8l,作为化盐,显示显著改善水溶性和有利的日志P值.
- 机理学研究表明,8l通过与菌素部位结合来抑制氨酸聚合,从而导致细胞循环停止和细胞亡.
- 在体内,8l与化合物相比,表现出强大的瘤生长抑制,细胞迁移减少,没有明显的毒性.
结论:
- 英达衍生物8l是一种强大的抗癌剂,具有改善的物理化学特性和疗效.
- 它通过破坏蛋白聚合来起作用,诱导细胞循环停止和细胞亡.
- 8l显示了作为癌症治疗中的治疗剂的进一步研究的巨大潜力.
相关概念视频
01:15Drugs that Stabilize Microtubules
2.1K
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.1K
01:10Drugs that Destabilize Microtubules
2.0K
Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.0K
01:45Destabilization of Microtubules
2.7K
The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
2.7K
01:23Microtubule Formation
5.8K
Microtubules are dynamic structures that undergo continuous assembly and disassembly. They originate from specialized multi-protein complexes known as microtubule organizing centers or MTOCs. Within the MTOC, the point of origin of the microtubule is known as the minus end, while the end radiating outward is the plus end. Microtubules serve two primary functions — the organization of spindle complexes to separate sister chromatids during mitotic or meiotic cell division and the formation...
5.8K
01:35Microtubules
87.5K
There are three types of cytoskeletal structures in eukaryotic cells—microfilaments, intermediate filaments, and microtubules. With a diameter of about 25 nm, microtubules are the thickest of these fibers. Microtubules carry out a variety of functions that include cell structure and support, transport of organelles, cell motility (movement), and the separation of chromosomes during cell division.
87.5K
01:32Microtubule Associated Motor Proteins
8.1K
Eukaryotic cells have different motor proteins for transporting various cargo within the cell. These motor proteins differ based on the filament they associate with, the direction they move within the cell, and the type of cargo they transport. Motor proteins that associate with microtubules are known as microtubule-associated motor proteins. There are two families of microtubule-associated motor proteins —Kinesins and Dyneins. Both these proteins assist in the transport of cellular...
8.1K