One-pot synthesis and cytotoxicity studies of new Mannich base derivatives of polyether antibiotic-Lasalocid acid

被引：23

作者：

Huczynski, Adam ^{[1
]}

Rutkowski, Jacek ^{[1
]}

Borowicz, Izabela ^{[1
]}

Wietrzyk, Joanna ^{[2
]}

Maj, Ewa ^{[2
]}

Brzezinski, Bogumil ^{[1
]}

机构：

[1] Adam Mickiewicz Univ, Fac Chem, PL-60780 Poznan, Poland

[2] Polish Acad Sci, Ludwik Hierszfeld Inst Immunol & Expt Therapy, PL-53114 Wroclaw, Poland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 18期

关键词：

Mannich bases synthesis; Lasalocid acid derivatives; Structural and spectroscopic studies; Antiproliferative activity; Polyether ionophores; Anticancer properties; OVARIAN-CANCER CELLS; ANTIBACTERIAL ACTIVITY; FT-IR; SALINOMYCIN; MONENSIN; COMPLEXES; CATIONS; ACTIVATION; MOLECULES; CHEMISTRY;

D O I：

10.1016/j.bmcl.2013.07.040

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Seven Mannich base derivatives of polyether antibiotic Lasalocid acid (2a-2g) were synthesized and screened for their antiproliferative activity against various human cancer cell lines. A novel chemoselective one-pot synthesis of these Mannich bases was developed. Compounds 2a-2c and 2g with sterically smaller dialkylamine substituent, displayed potent antiproliferative activity (IC50: 3.2-7.3 mu M), and demonstrated higher than twofold selectivity for specific type of cancer. The nature of Mannich base substituent on C-2 atom at the aromatic ring may be critical in the search for selectivity towards a particular cancer cell. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：5053 / 5056

页数：4

共 28 条

[1] Enantioselective Mannich-type reaction catalyzed by a chiral Bronsted acid [J].

Akiyama, T ;

Itoh, J ;

Yokota, K ;

Fuchibe, K .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (12) :1566-1568

[2] o-Aminomethylderivatives of phenols. Part 3. Mechanistic investigation of a Mannich reaction of phenols with N-methylenealkylamines [J].

Bujnowski, Krzysztof ;

Adamczyk-Wozniak, Agnieszka ;

Synoradzki, Ludwik .

ARKIVOC, 2008, :106-+

[3] o-aminomethyl derivatives of phenols.: Part 2.: Benzoxazines and dibenzylamines:: Properties, structure, synthesis and purification [J].

Bujnowski, Krzysztof ;

Adamczyk, Agnieszka ;

Synoradzki, Ludwik .

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL, 2007, 39 (05) :417-446

[4]

Dhaheri Y. A., 2013, BIOCH BIOPHYS ACTA G, V1830, P3121

[5] Salinomycin induces apoptosis and overcomes apoptosis resistance in human cancer cells [J].

Fuchs, Dominik ;

Heinold, Andreas ;

Opelz, Gerhard ;

Daniel, Volker ;

Naujokat, Cord .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2009, 390 (03) :743-749

[6] Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening [J].

Gupta, Piyush B. ;

Onder, Tamer T. ;

Jiang, Guozhi ;

Tao, Kai ;

Kuperwasser, Charlotte ;

Weinberg, Robert A. ;

Lander, Eric S. .

CELL, 2009, 138 (04) :645-659

[7] Synthesis and antimicrobial properties of Monensin A esters [J].

Huczynski, Adam ;

Stefanska, Joanna ;

Przybylski, Piotr ;

Brzezinski, Bogumil ;

Bartl, Franz .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (08) :2585-2589

[8] Synthesis, FT-IR, 1H, 13C NMR, ESI MS and PM5 studies of a new Mannich base of polyether antibiotic - Lasalocid acid and its complexes with Li+, Na+ and K+ cations [J].

Huczynski, Adam ;

Rutkowski, Jacek ;

Brzezinski, Bogumil ;

Bartl, Franz .

SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY, 2013, 104 :497-504

[9] X-ray crystallographic, FT-IR and NMR studies as well as anticancer and antibacterial activity of the salt formed between ionophore antibiotic Lasalocid acid and amines [J].

Huczynski, Adam ;

Rutkowski, Jacek ;

Wietrzyk, Joanna ;

Stefanska, Joanna ;

Maj, Ewa ;

Ratajczak-Sitarz, Malgorzata ;

Katrusiak, Andrzej ;

Brzezinski, Bogumil ;

Bartl, Franz .

JOURNAL OF MOLECULAR STRUCTURE, 2013, 1032 :69-77

[10] Antiproliferative activity of salinomycin and its derivatives [J].

Huczynski, Adam ;

Janczak, Jan ;

Antoszczak, Michal ;

Wietrzyk, Joanna ;

Maj, Ewa ;

Brzezinski, Bogumil .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (23) :7146-7150

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