Synthesis and Biological Evaluation of New Amino Acid and Dipeptide Derivatives of Neocryptolepine as Anticancer Agents

被引：43

作者：

Sidoryk, Katarzyna ^{[1
]}

Switalska, Marta ^{[2
]}

Wietrzyk, Joanna ^{[2
]}

Jaromin, Anna ^{[3
]}

Pietka-Ottlik, Magdalena ^{[4
]}

Cmoch, Piotr ^{[1
,5
]}

Zagrodzka, Joanna ^{[1
]}

Szczepek, Wojciech ^{[1
]}

Kaczmarek, Lukasz ^{[1
]}

Peczynska-Czoch, Wanda ^{[4
]}

机构：

[1] Pharmaceut Res Inst, PL-01793 Warsaw, Poland

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

[3] Univ Wroclaw, Fac Biotechnol, Dept Lipids & Liposomes, PL-51148 Wroclaw, Poland

[4] Wroclaw Univ Technol, Fac Chem, Div Organ Chem, PL-50370 Wroclaw, Poland

[5] Polish Acad Sci, Inst Organ Chem, PL-01224 Warsaw, Poland

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 55卷 / 11期

关键词：

TUMOR; ANTITUMOR; PHARMACOKINETICS; INDOLOQUINOLINES; TROVAFLOXACIN; DOXORUBICIN; PRODRUG;

D O I：

10.1021/jm300468t

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The syntheses of neocryptolepine derivatives containing an amino acid or a dipeptide at the C-9 position and their evaluation for antitumor activity in vitro and in vivo are reported. To establish the influence of an amino acid or a peptide on the physicochemical properties of 5H-indolo[2,3-b]quinoline (DiMIQ), lipophilic and hemolytic properties were investigated. Most of the compounds displayed a high antiproliferative activity in vitro and strongly inhibited growth of tumor in mice compared to cyclophosphamide. The attachment of the hydrophilic amino acid or the peptide to the hydrophobic DiMIQ increased its hydrophilic properties and decreased its hemolytic activity. The glycylglycine conjugate (7a) was the most promising derivative. It strongly inhibited the growth of the tumor in mice (at dose 50 mg kg(-1) day(-1) it inhibited the tumor growth by 46-63% on days 11-16 and by 29-43% on days 18-23) and significantly decreased hemolytic activity and lowered the in vivo toxicity compared to DiMIQ.

引用

页码：5077 / 5087

页数：11

共 28 条

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