含有的andrographolide衍生物在癌细胞中具有反转多药耐药性的效果
Joana R L Ribeiro1, Nikoletta Szemerédi2, Bruno M F Gonçalves1
1Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa Av. Prof. Gama Pinto 1649-003 Lisbon Portugal mjuferreira@ff.ulisboa.pt.
RSC medicinal chemistry
|April 26, 2024
概括
研究人员开发了来自andrographolide的新抗癌剂,以对抗多药性耐药性 (MDR). 几种化合物有效抑制了P-glycoprotein (P-gp),在癌症治疗中有望克服抗药性.
科学领域:
- 自然产品化学 自然产品化学
- 药用化学 医学化学
- 癌症药理学 癌症药理学
背景情况:
- 多药性耐药性 (MDR) 是有效的癌症化疗的一个重大障碍.
- 克服MDR需要新的治疗策略和可以逆转药物耐药性的药物.
研究的目的:
- 合成和评估新的andrographolide衍生物作为克服MDR的潜在药物.
- 为了研究P-glycoprotein (P-gp) 抑制活性和与多克索鲁比的协同效应.
主要方法:
- 通过迈克尔类添加和消除反应合成23种含有的andrographolide新衍生物.
- 使用1D和2DNMR光谱学进行结构阐明.
- 评估MDR逆转潜力使用功能和化学敏感性测试在耐药L5178Y小鼠淋巴瘤细胞,ATPase测试和抗增殖活性测试.
主要成果:
- 几种合成衍生物显示出显著的P-gp抑制活性.
- 化合物13和20 (thiosemicarbazide衍生物) 在2μM时显示出强大的MDR逆转.
- 化合物5表现出附带敏感性和强烈的抗扩散活性 (IC50 = 5.47 ± 0.22 μM).
- 所有测试的化合物都与多克索鲁比辛表现出协同作用,其中化合物3是最有效的.
结论:
- 新型andrographolide衍生物显示出克服癌症中MDR的显著潜力.
- 13,20和3的化合物是作为MDR逆转剂进一步开发的有希望的候选物.
- 化合物5的附带敏感性要求对向癌症治疗进行进一步调查.
更多相关视频
09:13Author Spotlight: Developing Multiplexed Kinetic Assays for Organoid-Based Drug Response Analysis
Published on: January 5, 2024
1.2K
19:44Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
Published on: May 30, 2012
18.7K
相关概念视频
02:57Targeted 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
02:56Treatment 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
01:15Drugs that Stabilize Microtubules
2.0K
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...
2.0K
02:50Combination 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
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
02:49Cancer 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