通过单一的氧气释放坎普托他-内氧化物克服多药性耐药性
Guangyu Zhang1, Lei Wang1, Yuan Qiao1
1State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Engineering, School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, P. R. China.
概括
坎普托素 (CPT) 的结构修改产生了释放单片氧的内氧化物 (ENDO-CPT). 这种ENDO-CPT衍生物显示出对抗多药耐药细胞系的改善细胞毒性.
科学领域:
- 药用化学 医学化学
- 有机化学 有机化学
- 癌症生物学 癌症生物学
背景情况:
- 坎普托西因 (CPT) 是一种强效的抗癌药物,但由于多药性耐药性 (MDR) 而面临限制.
- 研究了对CPT结构的修改,以克服抵抗机制并提高治疗疗效.
- P-glycoprotein (P-gp) 是一个关键的排泄,有助于各种癌症类型的MDR.
研究的目的:
- 合成和表征一种具有增强抗癌活性的新型坎普托塞辛衍生物.
- 调查内氧化物修饰的潜力,以改善药物输送和疗效.
- 评估改性化合物的细胞毒性对抗多药耐药性癌症细胞系.
主要方法:
- 通过在位置9和12添加甲基组,对坎普托素 (CPT) 进行结构修改.
- 修改后的CPT转换为内氧化物衍生物 (ENDO-CPT).
- 评估ENDO-CPT单片氧的热释放率及其在37°C的半衰期.
- 对MDR细胞系的细胞毒性评价与CPT和9,12-二甲基坎プト丁 (DM-CPT) 相比.
主要成果:
- 成功合成了一种新型的坎普托他的内氧化衍生物 (ENDO-CPT).
- ENDO-CPT通过热释放单片氧,在37°C时恢复为9,12-二甲基坎プト素 (DM-CPT),半衰期为1.4小时.
- 与CPT和DM-CPT相比,ENDO-CPT对MDR细胞系显著改善了细胞毒性.
结论:
- 坎普托丁的内氧化物修饰是一种有前途的策略,可以增强抗癌效果.
- 释放的单片氧和坎普托塞辛核的同时作用可能有效地准P-糖蛋白.
- 这种方法为克服癌症治疗中的多药耐药性提供了潜在的新途径.
相关概念视频
Treatment Resistant Cancers
3.3K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K
Combination Therapies and Personalized Medicine
4.9K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K
Cancer Therapies
7.6K
Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
7.6K
Targeted Cancer Therapies
7.5K
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...
7.5K
Electron Transport Chain: Complex I and II
12.1K
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...
12.1K


