Synthesis and structure-activity relationships study of cytotoxic bufalin 3-nitrogen-containing-ester derivatives

被引：38

作者：

Ma, Biao ^{[1
]}

Xiao, Zhi-Yong ^{[1
]}

Chen, Yi-Jia ^{[1
]}

Lei, Min ^{[1
]}

Meng, Yu-Hui ^{[1
]}

Guo, De-An ^{[1
]}

Liu, Xuan ^{[1
]}

Hu, Li-Hong ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Res Ctr Modernizat Tradit Chinese Med, Shanghai 201203, Peoples R China

来源：

STEROIDS | 2013年 / 78卷 / 05期

基金：

中国国家自然科学基金;

关键词：

Bufalin; 3-nitrogen-containing-ester; Structure-activity relationships; Cytotoxicity; BUFADIENOLIDES; CARCINOMA; DIGITOXIN; APOPTOSIS;

D O I：

10.1016/j.steroids.2013.02.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of bufalin 3-nitrogen-containing-ester derivatives (2-6) were designed, synthesized, and evaluated for their proliferation inhibition activities against human cervical epithelial adenocarcinoma (HeLa) and non-small-cell lung cancer (A549) cell lines. The structure-activity relationships (SARs) of this new series were described in this paper. Cytotoxicity data revealed that C3 moiety had important influence on cytotoxic activity. On two cell lines, the bufalin-3-piperidinyl-4-carboxylate compound 2 (IC50 values on HeLa and A549 cell lines were 0.76 nM and 0.34 nM, respectively) displayed a significant cytotoxic potency compared to the parent compound bufalin. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：508 / 512

页数：5

共 23 条

[1] Configurational Reassignment and Improved Preparation of the Competitive IL-6 Receptor Antagonist 20R,21R-Epoxyresibufogenin-3-formate [J].

Boos, Terrence L. ;

Cheng, Kejun ;

Greiner, Elisabeth ;

Deschamps, Jeffrey R. ;

Jacobson, Arthur E. ;

Rice, Kenner C. .

JOURNAL OF NATURAL PRODUCTS, 2012, 75 (04) :661-668

[2]

Brown E., 1998, Ring Nitrogen and Key Biomolecules: The Biochemistry of N-Heterocycles

[3]

Chueh FS, 2011, ENV TOXICOL

[4]

Elbaz HA, 2012, EXP HEMATOL ONCOL, V1, DOI 10.1186/2162-3619-1-4

[5] Rapid Structural Identification of Cytotoxic Bufadienolide Sulfates in Toad Venom from Bufo melanosticus by LC-DAD-MSn and LC-SPE-NMR [J].

Gao, Huimin ;

Zehl, Martin ;

Kaehlig, Hanspeter ;

Schneider, Peter ;

Stuppner, Hermann ;

Banuls, Laetitia Moreno Y. ;

Kiss, Robert ;

Kopp, Brigitte .

JOURNAL OF NATURAL PRODUCTS, 2010, 73 (04) :603-608

[6] Anti-tumor activities and apoptosis-regulated mechanisms of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice [J].

Han, Ke-Qi ;

Huang, Guang ;

Gu, Wei ;

Su, Yong-Hua ;

Huang, Xue-Qiang ;

Ling, Chang-Quan .

WORLD JOURNAL OF GASTROENTEROLOGY, 2007, 13 (24) :3374-3379

[7] EFFECTS OF BUFADIENOLIDES AND SOME KINDS OF CARDIOTONICS ON GUINEA-PIG HEARTS [J].

HIRAI, Y ;

MORISHITA, S ;

ITO, C ;

SAKANASHI, M .

FOLIA PHARMACOLOGICA JAPONICA, 1992, 100 (02) :127-135

[8] Synthesis and evaluation of cardiac glycoside mimics as potential anticancer drugs [J].

Jensen, Marie ;

Schmidt, Steffen ;

Fedosova, Natalya U. ;

Mollenhauer, Jan ;

Jensen, Henrik H. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2011, 19 (07) :2407-2417

[9] Effects of bufalin on the proliferation of human lung cancer cells and its molecular mechanisms of action [J].

Jiang, Yongtao ;

Zhang, Ying ;

Luan, Jinling ;

Duan, Huiying ;

Zhang, Feng ;

Yagasaki, Kazumi ;

Zhang, Guoying .

CYTOTECHNOLOGY, 2010, 62 (06) :573-583

[10] QSAR evaluation of the Ch'an Su and related bufadienolides against the colchicine-resistant primary liver carcinoma cell line PLC/PRF/51 [J].

Kamano, Y ;

Yamashita, A ;

Nogawa, T ;

Morita, H ;

Takeya, K ;

Itokawa, H ;

Segawa, T ;

Yukita, A ;

Saito, K ;

Katsuyama, M ;

Pettit, GR .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (25) :5440-5447

← 1 2 3 →