4,5-Diaryl-3-aminopyrazole Derivatives as Analogs of Combretastatin A-4: Synthesis and Biological Evaluation

被引：20

作者：

Liu, Tao ^{[1
]}

Cui, Rong ^{[1
,2
]}

Chen, Jing ^{[1
]}

Zhang, Jun ^{[3
]}

He, Qiaojun ^{[3
]}

Yang, Bo ^{[3
]}

Hu, Yongzhou ^{[1
]}

机构：

[1] Zhejiang Univ, Coll Pharmaceut Sci, ZJU ENS Joint Lab Med Chem, Hangzhou 310058, Zhejiang, Peoples R China

[2] JinHua Coll Vocat & Technol, Jinhua, Peoples R China

[3] Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmacol & Toxicol, Hangzhou 310058, Zhejiang, Peoples R China

来源：

ARCHIV DER PHARMAZIE | 2011年 / 344卷 / 05期

关键词：

Antitumor agents; Combretastatin A-4 analogs; Cytotoxicity; 4,5-Diaryl-3-aminopyrazole derivatives; CIS-RESTRICTED ANALOGS; ANTITUMOR AGENTS; ANTINEOPLASTIC AGENTS; TUBULIN; COLCHICINE; DESIGN; INHIBITORS; BINDING; GROWTH;

D O I：

10.1002/ardp.201000069

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of cis-restricted 4,5-diaryl-3-aminopyrazole derivatives were synthesized and tested for their cytotoxic activity in vitro against five human cancer cell lines (K562, ECA-109, A549, SMMC-7721, and PC-3). Compounds 5a, 5b, 5d, and 6b showed potent cytotoxicity against all tested cell lines. Primary mechanism research on compound 5a indicated that it was a potent inhibitor of tubulin polymerization, arresting cell cycle in G(2)/M phase. The docking research showed the conformation of 5a overlaps well with CA-4 in the crystallized protein complex, suggesting the 4,5-diaryl-3-aminopyrazoles were good mimics of CA-4.

引用

页码：279 / 286

页数：8

共 50 条

[31] Synthesis of Combretastatin A-4 and 3′-Aminocombretastatin A-4 derivatives with Aminoacid Containing Pendants and Study of their Interaction with Tubulin and as Downregulators of the VEGF, hTERT and c-Myc Gene Expression [J].

Agut, Raul ;

Falomir, Eva ;

Murga, Juan ;

Martin-Beltran, Celia ;

Gil-Edo, Raquel ;

Pla, Alberto ;

Carda, Miguel ;

Marco, J. Alberto .

MOLECULES, 2020, 25 (03)

[32] Synthesis and evaluation of antiproliferative microtubule-destabilising combretastatin A-4 piperazine conjugates [J].

O'Boyle, Niamh M. ;

Ana, Gloria ;

Kelly, Patrick M. ;

Nathwani, Seema M. ;

Noorani, Sara ;

Fayne, Darren ;

Bright, Sandra A. ;

Twamley, Brendan ;

Zisterer, Daniela M. ;

Meegan, Mary J. .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2019, 17 (25) :6184-6200

[33] Design, synthesis, and biological evaluation of novel combretastatin A-4 thio derivatives as microtubule targeting agents [J].

Stefanski, Tomasz ;

Mikstacka, Renata ;

Kurczab, Rafal ;

Dutkiewicz, Zbigniew ;

Kucinska, Malgorzata ;

Murias, Marek ;

Zielinska-Przyjemska, Malgorzata ;

Cichocki, Michal ;

Teubert, Anna ;

Kaczmarek, Mariusz ;

Hogendorf, Adam ;

Sobiak, Stanislaw .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2018, 144 :797-816

[34] Synthesis and antiproliferative evaluation of novel benzoimidazole-contained oxazole-bridged analogs of combretastatin A-4 [J].

Zhou, Jie ;

Jin, Jing ;

Zhang, Yi ;

Yin, Yuwen ;

Chen, Xiaoguang ;

Xu, Bailing .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2013, 68 :222-232

[35] Synthesis of novel spin-labelled combretastatin A-4 derivatives as potential antineoplastic agents [J].

Li, Xiao-Jing ;

Yang, Liu ;

Liu, Ying-Qian ;

Li, Chong .

NATURAL PRODUCT RESEARCH, 2012, 26 (14) :1271-1277

[36] A diaryl sulfide, sulfoxide, and sulfone bearing structural similarities to combretastatin A-4 [J].

Barbosa, Euzebio G. ;

Bega, Luis A. S. ;

Beatriz, Adilson ;

Sarkar, Taradas ;

Hamel, Ernest ;

do Amaral, Marcos S. ;

de Lima, Denis Pires .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2009, 44 (06) :2685-2688

[37] In vitro and in vivo biological evaluation of new 4,5-disubstituted 1,2,3-triazoles as cis-constrained analogs of combretastatin A4 [J].

Blanch, Nuria Mur ;

Chabot, Guy G. ;

Quentin, Lionel ;

Scherman, Daniel ;

Bourg, Stephane ;

Dauzonne, Daniel .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2012, 54 :22-32

[38] Combretastatin a-4 analogs as anticancer agents [J].

Chaudhary, Anurag ;

Pandeya, S. N. ;

Kumar, P. ;

Sharma, Py. ;

Gupta, S. ;

Soni, N. ;

Verma, K. K. ;

Bhardwaj, G. .

MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2007, 7 (12) :1186-1205

[39] Synthesis and biological activity of pyrrole analogues of combretastatin A-4 [J].

Jung, Eun-Kyung ;

Leung, Euphemia ;

Barker, David .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2016, 26 (13) :3001-3005

[40] Design, synthesis, and biological evaluation of pyrazole-based combretastatin A-4 analogues as potential cytotoxic agents [J].

Omar, Mai H. ;

Emam, Soha H. ;

Mikhail, Demiana S. ;

Elmeligie, Salwa .

BIOORGANIC CHEMISTRY, 2025, 163

← 1 2 3 4 5 →