Synthesis of novel pyrazole carboxamide derivatives and discovery of modulators for apoptosis or autophagy in A549 lung cancer cells

被引：47

作者：

Ding, Xiao-Ling ^{[1
,3
]}

Zhang, Hai-Yan ^{[2
]}

Qi, Lei ^{[2
]}

Zhao, Bao-Xiang ^{[1
]}

Lian, Song ^{[1
]}

Lv, Hong-Shui ^{[1
]}

Miao, Jun-Ying ^{[2
]}

机构：

[1] Shandong Univ, Sch Chem & Chem Engn, Inst Organ Chem, Jinan 250100, Peoples R China

[2] Shandong Univ, Sch Life Sci, Inst Dev Biol, Jinan 250100, Peoples R China

[3] Qingdao Univ, Coll Adv Profess Technol, Qingdao 266061, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 18期

基金：

中国国家自然科学基金;

关键词：

Pyrazole; Carboxamide; A549; cells; Apoptosis; Autophagy; BIOLOGICAL EVALUATION; RECEPTOR ANTAGONISTS; POTENTIAL AGENTS; DESIGN; INHIBITORS;

D O I：

10.1016/j.bmcl.2009.07.131

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel 3-aryl-1-arylmethyl-1H-pyrazole-5-carboxamide derivatives 3a-1, were synthesized by the reaction of 3-aryl-1-arylmethyl-1H-pyrazole-5-carbonyl chloride with substituted amine in excellent yields. The compounds 3e-h could suppress A549 lung cancer cell growth, More interestingly, compounds 3e and 3f might inhibit the A549 cell growth by inducing apoptosis; whereas compounds 3g and 3h with fluorine group might inhibit the A549 cell growth by inducing autophagy. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：5325 / 5328

页数：4

共 27 条

[11] Role of autophagy in breast cancer [J].

Karantza-Wadsworth, Vassiliki ;

White, Eileen .

AUTOPHAGY, 2007, 3 (06) :610-613

[12] Design and synthesis of substituted 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxamides, novel HIV-1 integrase inhibitors [J].

Langford, H. Marie ;

Williams, Peter D. ;

Homnick, Carl F. ;

Vacca, Joseph P. ;

Felock, Peter J. ;

Stillmock, Kara A. ;

Witmer, Marc V. ;

Hazuda, Daria J. ;

Gabryelski, Lori J. ;

Schleif, William A. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (02) :721-725

[13] Cell biology - Autophagy and cancer [J].

Levine, Beth .

NATURE, 2007, 446 (7137) :745-747

[14] Apoptosis in cancer [J].

Lowe, SW ;

Lin, AW .

CARCINOGENESIS, 2000, 21 (03) :485-495

[15] Rational design, synthesis and biological evaluation of new 1,5-diarylpyrazole derivatives as CB1 receptor antagonists, structurally related to rimonabant [J].

Menozzi, Giulia ;

Fossa, Paola ;

Cichero, Elena ;

Spallarossa, Andrea ;

Ranise, Angelo ;

Mosti, Luisa .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2008, 43 (12) :2627-2638

[16] Autophagy: process and function [J].

Mizushima, Noboru .

GENES & DEVELOPMENT, 2007, 21 (22) :2861-2873

[17]

Paglin S, 2001, CANCER RES, V61, P439

[18] Pyrazole inhibitors of coactivator associated arginine methyltransferase 1 (CARM1) [J].

Purandare, Ashok V. ;

Chen, Zhong ;

Huynh, Tram ;

Pang, Suhong ;

Geng, Jieping ;

Vaccaro, Wayne ;

Poss, Michael A. ;

Oconnell, Jonathan ;

Nowak, Kimberly ;

Jayaraman, Lata .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (15) :4438-4441

[19] Achieving structural diversity using the perpendicular conformation of alpha-substituted phenylcyclopropanes to mimic the bioactive conformation of ortho-substituted biphenyl P4 moieties:: Discovery of novel, highly potent inhibitors of Factor Xa [J].

Qiao, Jennifer X. ;

Cheney, Daniel L. ;

Alexander, Richard S. ;

Smallwood, Angela M. ;

King, Sarah R. ;

He, Kan ;

Rendina, Alan R. ;

Luettgen, Joseph M. ;

Knabb, Robert M. ;

Wexler, Ruth R. ;

Lam, Patrick Y. S. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (14) :4118-4123

[20] Highly efficacious factor Xa inhibitors containing α-substituted phenylcycloalkyl P4 moieties [J].

Qiao, Jennifer X. ;

King, Sarah R. ;

He, Kan ;

Wong, Pancras C. ;

Rendina, Alan R. ;

Luettgen, Joseph M. ;

Xin, Baomin ;

Knabb, Robert M. ;

Wexler, Ruth R. ;

Lam, Patrick Y. S. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (02) :462-468

← 1 2 3 →