2. Academic Validation
  3. Synthesis and anti-cancer evaluation of folic acid-peptide- paclitaxel conjugates for addressing drug resistance

Synthesis and anti-cancer evaluation of folic acid-peptide- paclitaxel conjugates for addressing drug resistance

  • Eur J Med Chem. 2019 Jun 1:171:104-115. doi: 10.1016/j.ejmech.2019.03.031.
Yuxuan Dai 1,  Xingguang Cai 1,  Xinzhou Bi 1,  Chunxia Liu 1,  Na Yue 1,  Ying Zhu 1,  Jiaqi Zhou 1,  Mian Fu 2,  Wenlong Huang 3,  Hai Qian 4
Affiliations

Affiliations

  • 1 Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
  • 2 Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Department of Biochemistry and Molecular Biology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, PR China.
  • 3 Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
  • 4 Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China. Electronic address: qianhai24@163.com.
PMID: 30913525 DOI: 10.1016/j.ejmech.2019.03.031
Abstract

The drug resistance and the poor water solubility are major limitations of paclitaxel (PTX) of based chemotherapy. To conquer the two problems, targeting folate (FA) receptor PTX-lytic Peptides conjugates were synthesized and evaluated. Compared with PTX, FA-P3-PTX and FA-P7-PTX displayed significantly enhanced cell toxicity in many Cancer cells, particularly drug resistant Cancer cells MCF-7/PTX. FA-P7-PTX possessed stronger effect on cell toxicity (IC50 = 2.92 ± 0.2 μM), membrane disrupting activity and pro-apoptosis in MCF-7/PTX cells than FA-P3-PTX. Further investigation displayed that the anti-cancer mechanisms of FA-P3-PTX and FA-P7-PTX might be a mitochondrial impairment and caspase-3-dependent apoptotic cell death. Furthermore, the in vivo antitumor efficacy study confirmed that FA-P7-PTX performed more stronger potency in inhibition of tumors growth than PTX. The study demonstrated that conjugate FA-P7-PTX with superior properties for antineoplastic activity, which makes it a promising potential candidate for drug-resistant Cancer therapy.

Keywords

Apoptosis; Conjugates of paclitaxel; Drug resistance; Folate receptor targeted; Lytic peptides; Membranolytic; Paclitaxel.

Figures
我们的 Cookie 政策

我们使用 Cookies 和类似技术以提高网站的性能和提升您的浏览体验，部分功能也使用 Cookies 帮助我们更好地理解您的需求，为您提供相关的服务。 如果您有任何关于我们如何处理您个人信息的疑问，请阅读我们的《隐私声明》。

嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z