Novel naphthalimide derivatives as potential apoptosis-inducing agents: Design, synthesis and biological evaluation

被引：40

作者：

Wu, Aibin ^{[1
]}

Xu, Yufang ^{[1
]}

Qian, Xuhong ^{[1
]}

Wang, Jin ^{[1
]}

Liu, Jianwen ^{[1
]}

机构：

[1] E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 11期

基金：

国家高技术研究发展计划(863计划); 中国国家自然科学基金;

关键词：

Naphthalimide; Antitumor; Cytotoxicity; G(2)/M arrest; Apoptosis; CELL-CYCLE; INHIBITORS; BCL-2; DISCOVERY; GROWTH; DNA; PROLIFERATION; INTERCALATORS; CYTOTOXICITY; PROTEINS;

D O I：

10.1016/j.ejmech.2009.07.011

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel naphthalimide derivatives with flexible alkyl/aryl moieties were designed and synthesized. Their antitumor activities were evaluated against HeLa, A549, P388, HL-60, MCF-7, HCT-8 and A375 cancer cell lines in vitro. The preliminary results showed that most of the derivatives had comparable antitumor activities over Amonafide with the IC50 values of 10(-6) to 10(-5) M. More importantly, flow cytometric analysis indicated that the derivatives could effectively induce G(2)/M arrest and progress to apoptosis in HL-60 cell line after double staining with annexin V-FITC and propidium iodide. The present work provided a novel class of naphthalimide-based derivatives with potent apoptosis-inducing and antitumor activities for further optimization. (C) 2009 Elsevier Masson SAS. All rights reserved.

引用

页码：4674 / 4680

页数：7

共 43 条

[1] Substituted E-3-(2-chloro-3-indolylmethylene)1,3-dihydroindol-2-ones with antitumor activity.: Effect on the cell cycle and apoptosis [J].

Andreani, Aldo ;

Burnelli, Silvia ;

Granaiola, Massimiliano ;

Leoni, Alberto ;

Locatelli, Alessandra ;

Morigi, Rita ;

Rambaldi, Mirella ;

Varoli, Lucilla ;

Calonghi, Natalia ;

Cappadone, Concettina ;

Farruggia, Giovanna ;

Zini, Maddalena ;

Stefanelli, Claudio ;

Masotti, Lanfranco .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (14) :3167-3172

[2] Synthesis, biological activity, and quantitative structure-activity relationship study of azanaphthalimide and arylnaphthalimide derivatives [J].

Braña, MF ;

Gradillas, A ;

Gómez, A ;

Acero, N ;

Llinares, F ;

Muñoz-Mingarro, D ;

Abradelo, C ;

Rey-Stolle, F ;

Yuste, M ;

Campos, J ;

Gallo, MA ;

Espinosa, A .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (09) :2236-2242

[3] Intercalators as anticancer drugs [J].

Braña, MF ;

Cacho, M ;

Gradillas, A ;

de Pascual-Teresa, B ;

Ramos, A .

CURRENT PHARMACEUTICAL DESIGN, 2001, 7 (17) :1745-1780

[4] Studies leading to potent, dual inhibitors of bcl-2 and Bcl-xL [J].

Bruncko, Milan ;

Oost, Thorsten K. ;

Belli, Barbara A. ;

Ding, Hong ;

Joseph, Mary K. ;

Kunzer, Aaron ;

Martineau, Darlene ;

McClellan, William J. ;

Mitten, Michael ;

ng, Shi-Chu Ng ;

Nimmer, Paul M. ;

Oltersdorf, Tilman ;

Park, Cheol-Min ;

Petros, Andrew M. ;

Shoemaker, Alexander R. ;

Song, Xiaohong ;

Wang, Xilu ;

Wendt, Michael D. ;

Zhang, Haichao ;

Fesik, Stephen W. ;

Rosenberg, Saul H. ;

Elmore, Steven W. .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (04) :641-662

[5] Cell death: Critical control points [J].

Danial, NN ;

Korsmeyer, SJ .

CELL, 2004, 116 (02) :205-219

[6] An adamantyl-substituted retinoid-derived molecule that inhibits cancer cell growth and angiogenesis by inducing apoptosis and binds to small heterodimer partner nuclear receptor: Effects of modifying its carboxylate group on apoptosis, proliferation, and protein-tyrosine phosphatase activity [J].

Dawson, Marcia I. ;

Xia, Zebin ;

Liu, Gang ;

Fontana, Joseph A. ;

Farhana, Lulu ;

Patel, Bhamik B. ;

Arumugarajah, Sankari ;

Bhuiyan, Mohammad ;

Zhang, Xiao-Kun ;

Han, Young-Hoon ;

Stallcup, William B. ;

Fukushi, Jun-Ichi ;

Mustelin, Tomas ;

Tautz, Lutz ;

Su, Ying ;

Harris, Danni L. ;

Waleh, Nahid ;

Hobbs, Peter D. ;

Jong, Ling ;

Chao, Wan-ru ;

Schiff, Leonard J. ;

Sani, Brahma P. .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (11) :2622-2639

[7] Antiproliferative and apoptosis-inducing activities of alkyl gallate and gallamide derivatives related to (-)-epigallocatechin gallate [J].

Dodo, Kosuke ;

Minato, Taro ;

Noguchi-Yachide, Tomomi ;

Suganuma, Masami ;

Hashimoto, Yuichi .

BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (17) :7975-7982

[8]

FREI E, 1988, CANCER RES, V48, P6417

[9] Structure-activity relationships of Bak derived peptides: Affinity and specificity modulations by amino acid replacement [J].

Frey, Virginie ;

Viaud, Julien ;

Subra, Guy ;

Cauquil, Nicolas ;

Guichou, Jean-Francois ;

Casara, Patrick ;

Grassy, Gerard ;

Chavanieu, Alain .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2008, 43 (05) :966-972

[10] DNA and its associated processes as targets for cancer therapy [J].

Hurley, LH .

NATURE REVIEWS CANCER, 2002, 2 (03) :188-200

← 1 2 3 4 5 →