Design, synthesis, and testing of an isoquinoline-3-carboxylic-based novel anti-tumor lead

被引：14

作者：

Gao, Fei ^{[1
]}

Liu, Haiqing ^{[1
]}

Li, Li ^{[1
]}

Guo, Jianpeng ^{[1
]}

Wang, Yuji ^{[1
]}

Zhao, Ming ^{[1
,2
]}

Peng, Shiqi ^{[1
]}

机构：

[1] Capital Med Univ, Beijing Lab Biomed Mat, Beijing Area Major Lab Peptide & Small Mol Drugs, Engn Res Ctr,Minist Educ China,Coll Pharmaceut Sc, Beijing 100069, Peoples R China

[2] Kaohsiung Med Univ, Fac Biomed Sci & Environm Biol, Kaohsiung, Taiwan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 20期

基金：

北京市自然科学基金; 中国国家自然科学基金;

关键词：

Isoquinoline-3-carboxylic acid; Anti-tumor; Benzoic acid; Multiple pharmacophores; Tris(2-aminoethyl)amine; POTENT; ANTAGONISTS; INHIBITORS;

D O I：

10.1016/j.bmcl.2015.09.014

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Compound 6, a novel isoquinoline comprising two isoquinoline-3-carboxylic acids and a benzoic acid conjugated together using tris(2-aminoethyl) amine, was synthesized and tested for anti-tumor activity. In vivo evaluations found 6 to be well tolerated, of high therapeutic efficacy and of low systemic toxicity, at effective doses. The results suggest 6 to be a promising lead for future study, and the use of multiple isoquinoline-3-carboxylic acid moieties as pharmacophores in the same molecule to be a useful strategy for the design of anti-tumor drugs. (C) 2015 Elsevier Ltd. All rights reserved.

引用

收藏

页码：4434 / 4436

页数：3

相关论文

共 25 条

[11] Synthesis and biological evaluation of a small molecule library of 3rd generation multidrug resistance modulators [J].

Klinkhammer, Werner ;

Mueller, Henrik ;

Globisch, Christoph ;

Pajeva, Ilza K. ;

Wiese, Michael .

BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (06) :2524-2535

[12] Synthesis and structure-activity relationship of 4-substituted 2-(2-acetyloxyethyl)-8-(morpholine-4-sulfonyl)pyrrolo[3,4-c]quinoline-1,3-diones as potent caspase-3 inhibitors [J].

Kravchenko, DV ;

Kuzovkova, YA ;

Kysil, VM ;

Tkachenko, SE ;

Maliarchouk, S ;

Okun, IM ;

Balakin, KV ;

Ivachtchenko, AV .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (11) :3680-3683

[13] Global, local and novel consensus quantitative structure-activity relationship studies of 4-(Phenylaminomethylene) isoquinoline-1, 3 (2H, 4H)-diones as potent inhibitors of the cyclin-dependent kinase 4 [J].

Lei, Beilei ;

Xi, Lili ;

Li, Jiazhong ;

Liu, Huanxiang ;

Yao, Xiaojun .

ANALYTICA CHIMICA ACTA, 2009, 644 (1-2) :17-24

[14] In vivo effects of fluconazole on lymphocyte subpopulations of the thymus and spleen in mice: Flow cytometry analysis [J].

Liu, J ;

Mengel, K ;

Friedberg, KD .

INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY, 1996, 18 (8-9) :449-457

[15] Derivatives of 7-amino-1,2,3,4-tetrahydroisoquinoline and isophthalic acids as novel fibrinogen receptor antagonists [J].

Malovichko, Olga L. ;

Petrus, Anna S. ;

Krysko, Andrei A. ;

Kabanova, Tatyana A. ;

Andronati, Sergel A. ;

Karaseva, Tamara L. ;

Kirlyak, Anna V. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (20) :5294-5297

[16] Drug development from marine natural products [J].

Molinski, Tadeusz F. ;

Dalisay, Doralyn S. ;

Lievens, Sarah L. ;

Saludes, Jonel P. .

NATURE REVIEWS DRUG DISCOVERY, 2009, 8 (01) :69-85

[17] Investigation of the lactam side chain length necessary for optimal indenoisoquinoline topoisomerase i inhibition and cytotoxicity in human cancer cell cultures [J].

Morrell, Andrew ;

Placzek, Michael S. ;

Steffen, Jamin D. ;

Antony, Smitha ;

Agama, Keli ;

Pommier, Yves ;

Cushman, Mark .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (09) :2040-2048

[18] Hijacking a hydroxyethyl unit from a central metabolic ketose into a nonribosomal peptide assembly line [J].

Peng, Chao ;

Pu, Jin-Yue ;

Song, Li-Qiang ;

Jian, Xiao-Hong ;

Tang, Man-Cheng ;

Tang, Gong-Li .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (22) :8540-8545

[19] Effects of higenamine and its 1-naphthyl analogs, YS-49 and YS-51, on platelet TXA2 synthesis and aggregation [J].

Pyo, Mi Kyung ;

Kim, Jeong Mi ;

Jin, Jing-Ling ;

Chang, Ki Churl ;

Lee, Duck Hyung ;

Yun-Choi, Hye Sook .

THROMBOSIS RESEARCH, 2007, 120 (01) :81-86

[20] Biomimetic divalent ligands for the acute disruption of synaptic AMPAR stabilization [J].

Sainlos, Matthieu ;

Tigaret, Cezar ;

Poujol, Christel ;

Olivier, Nelson B. ;

Bard, Lucie ;

Breillat, Christelle ;

Thiolon, Kevin ;

Choquet, Daniel ;

Imperiali, Barbara .

NATURE CHEMICAL BIOLOGY, 2011, 7 (02) :81-91