Design and multi-step synthesis of chalcone-polyamine conjugates as potent antiproliferative agents

被引：16

作者：

Rioux, Benjamin ^{[1
]}

Pouget, Christelle ^{[1
]}

Fidanzi-Dugas, Chloe ^{[1
]}

Gamond, Aurelie ^{[1
]}

Laurent, Aurelie ^{[1
]}

Semaan, Josiane ^{[1
]}

Pinon, Aline ^{[1
]}

Champavier, Yves ^{[2
]}

Leger, David Y. ^{[1
]}

Liagre, Bertrand ^{[1
]}

Duroux, Jean-Luc ^{[1
]}

Fagnere, Catherine ^{[1
]}

Sol, Vincent ^{[1
]}

机构：

[1] Univ Limoges, Lab Chim Subst Nat, EA 1069, F-87000 Limoges, France

[2] Univ Limoges, BISCEm, F-87000 Limoges, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 18期

关键词：

Chalcones; Polyamines; Organic synthesis; Antiproliferative activity; Prostate and colorectal cancer cell lines; TARGETING TOPOISOMERASE-II; PROSTATE-CANCER CELLS; BIOLOGICAL EVALUATION; INDUCED APOPTOSIS; TRANSPORT-SYSTEM; DERIVATIVES; PATHWAY; CYTOTOXICITY; RESISTANCE; INHIBITORS;

D O I：

10.1016/j.bmcl.2017.08.024

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The aim of this study is to synthesize chalcone-polyamine conjugates in order to enhance bioavailability and selectivity of chalcone core towards cancer cells, using polyamine-based vectors. 3-hydroxy-3',4,4',5'-tetramethoxychalcone (1) and 3',4,4',5'-tetramethoxychalcone (2) were selected as parent chalcones since they were found to be efficient anti-proliferative agents on various cancer cells. A series of ten chalcone-polyamine conjugates was obtained by reacting carboxychalcones with different polyamine tails. Chalcones 1 and 2 showed a strong cytotoxic activity against two prostatic cancer (PC-3 and DU-145) and two colorectal cancer (HT-29 and HCT-116) cell lines. Then, chalcone-spermine conjugates 7d and 8d were shown to be the most active of the series and could be considered as promising compounds for colon and prostatic cancer adjuvant therapy. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：4354 / 4357

页数：4

共 35 条

[1] F14512, a Potent Antitumor Agent Targeting Topoisomerase II Vectored into Cancer Cells via the Polyamine Transport System [J].

Barret, Jean-Marc ;

Kruczynski, Anna ;

Vispe, Stephane ;

Annereau, Jean-Philippe ;

Brel, Viviane ;

Guminski, Yves ;

Delcros, Jean-Guy ;

Lansiaux, Amelie ;

Guilbaud, Nicolas ;

Imbert, Thierry ;

Bailly, Christian .

CANCER RESEARCH, 2008, 68 (23) :9845-9853

[2] Synthesis of extended conjugated indolyl chalcones as potent anti-breast cancer, anti-inflammatory and antioxidant agents [J].

Bhale, Pravin S. ;

Chavan, Hemant V. ;

Dongare, Sakharam B. ;

Shringare, Sadanand N. ;

Mule, Yoginath B. ;

Nagane, Samadhan S. ;

Bandgar, Babasaheb P. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2017, 27 (07) :1502-1507

[3] Practical synthesis of unsymmetrical polyamine amides [J].

Blagbrough, IS ;

Geall, AJ .

TETRAHEDRON LETTERS, 1998, 39 (5-6) :439-442

[4] A novel chalcone derivative which acts as a microtubule depolymerising agent and an inhibitor of P-gp and BCRP in in-vitro and in-vivo glioblastoma models [J].

Boumendjel, Ahcene ;

McLeer-Florin, Anne ;

Champelovier, Pierre ;

Allegro, Diane ;

Muhammad, Dima ;

Souard, Florence ;

Derouazi, Madiha ;

Peyrot, Vincent ;

Toussaint, Bertrand ;

Boutonnat, Jean .

BMC CANCER, 2009, 9

[5] Cytotoxicity and cell death mechanisms induced by the polyamine-vectorized anti-cancer drug F14512 targeting topoisomerase II [J].

Brel, Viviane ;

Annereau, Jean-Philippe ;

Vispe, Stephane ;

Kruczynski, Anna ;

Bailly, Christian ;

Guilbaud, Nicolas .

BIOCHEMICAL PHARMACOLOGY, 2011, 82 (12) :1843-1852

[6] Design, synthesis and antimalarial/anticancer evaluation of spermidine linked artemisinin conjugates designed to exploit polyamine transporters in Plasmodium falciparum and HL-60 cancer cell lines [J].

Chadwick, James ;

Jones, Michael ;

Mercer, Amy E. ;

Stocks, Paul A. ;

Ward, Stephen A. ;

Park, B. Kevin ;

O'Neill, Paul M. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2010, 18 (07) :2586-2597

[7] Design, Synthesis, and Biological Evaluation of Mitochondria Targeted Flavone-Naphthalimide- Polyamine Conjugates with Antimetastatic Activity [J].

Dai, Fujun ;

Li, Qian ;

Wang, Yuxia ;

Ge, Chaochao ;

Feng, Chenyang ;

Xie, Songqiang ;

He, Haoying ;

Xu, Xiaojuan ;

Wang, Chaojie .

JOURNAL OF MEDICINAL CHEMISTRY, 2017, 60 (05) :2071-2083

[8] Potent antimitotic and cell growth inhibitory properties of substituted chalcones [J].

Ducki, S ;

Forrest, R ;

Hadfield, JA ;

Kendall, A ;

Lawrence, NJ ;

McGown, AT ;

Rennison, D .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (09) :1051-1056

[9] Isolation of E-1-(4'-hydroxyphenyl)-but-1-en-3-one from Scutellaria barbata [J].

Ducki, S ;

Hadfield, JA ;

Lawrence, NJ ;

Liu, CY ;

McGown, AT ;

Zhang, XG .

PLANTA MEDICA, 1996, 62 (02) :185-186

[10] Combretastatin-like chalcones as inhibitors of microtubule polymerization. Part 1: Synthesis and biological evaluation of antivascular activity [J].

Ducki, Sylvie ;

Rennison, David ;

Woo, Meiko ;

Kendall, Alexander ;

Chabert, Jeremie Fournier Dit ;

McGown, Alan T. ;

Lawrence, Nicholas J. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (22) :7698-7710

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