Cytotoxic betulin-derived hydroxypropargylamines trigger apoptosis

被引：35

作者：

Csuk, Rene ^{[1
]}

Sczepek, Ronny ^{[1
]}

Siewert, Bianka ^{[1
]}

Nitsche, Christoph ^{[1
]}

机构：

[1] Univ Halle Wittenberg, Bereich Organ Chem, D-06120 Halle, Saale, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2013年 / 21卷 / 02期

关键词：

Betulin; Hydroxypropargylamines; Mannich reaction; Cancer; SRB assay; Antitumor; DNA laddering; Annexin V assay; Apoptosis; NATURAL-PRODUCT BETULIN; MANNICH-BASES; BIOLOGICAL-ACTIVITY; EFFICIENT SYNTHESIS; ACID-DERIVATIVES; PHARMACOLOGICAL PROSPECTS; LUPANE DERIVATIVES; POLYMER SYNTHESIS; HUMAN-MELANOMA; IN-VITRO;

D O I：

10.1016/j.bmc.2012.11.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Several novel betulin derivatives were prepared and evaluated for their antitumor activity. Among others, 3-O-acetylbetulinic aldehyde served as an ideal starting material for the synthesis of 28-acetylenic derivatives that were further transformed into Mannich bases. These hydroxypropargylamines were screened for their antitumor activity in a panel of nine human cancer cell lines in a sulforhodamine B (SRB) assay. Several compounds showed a noteworthy antitumor activity. The results from acridine orange/propidium iodide staining and annexinV-FITC assays as well as DNA laddering experiments provided evidence for an apoptotic cell death. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：425 / 435

页数：11

共 76 条

[1]

Pharmacological properties of the ubiquitous natural product betulin [J].

Alakurtti, Sami ;

Makela, Taru ;

Koskimies, Salme ;

Yli-Kauhaluoma, J. .

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2006, 29 (01) :1-13

[2]

ANGIOLINI L, 1985, POLYM COMMUN, V26, P218

[3]

Oxidation of betulin and its monoacetates by "activated" DMSO [J].

Ashavina, OY ;

Flekhter, OB ;

Galin, FZ ;

Kabal'nova, NN ;

Baltina, LA ;

Tolstikov, GA .

CHEMISTRY OF NATURAL COMPOUNDS, 2003, 39 (02) :207-211

[4]

Oxidative transformations of betulinol [J].

Barthel, Alexander ;

Stark, Sebastian ;

Csuk, Rene .

TETRAHEDRON, 2008, 64 (39) :9225-9229

[5]

Mild and efficient synthesis of propargylamines by copper-catalyzed Mannich reaction [J].

Bieber, LW ;

da Silva, MF .

TETRAHEDRON LETTERS, 2004, 45 (45) :8281-8283

[6]

Solubilities of Betulinic Acid in Thirteen Organic Solvents at Different Temperatures [J].

Cheng, Yong ;

Shao, Yundong ;

Yan, Weidong .

JOURNAL OF CHEMICAL AND ENGINEERING DATA, 2011, 56 (12) :4587-4591

[7]

Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection [J].

Cichewicz, RH ;

Kouzi, SA .

MEDICINAL RESEARCH REVIEWS, 2004, 24 (01) :90-114

[8]

Tormentic acid derivatives: Synthesis and apoptotic activity [J].

Csuk, Rene ;

Siewert, Bianka ;

Dressel, Christian ;

Schaefer, Renate .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2012, 56 :237-245

[9]

Synthesis, Encapsulation and Antitumor Activity of New Betulin Derivatives [J].

Csuk, Rene ;

Barthel, Alexander ;

Sczepek, Ronny ;

Siewert, Bianka ;

Schwarz, Stefan .

ARCHIV DER PHARMAZIE, 2011, 344 (01) :37-49

[10]

Synthesis, cytotoxicity and liposome preparation of 28-acetylenic betulin derivatives [J].

Csuk, Rene ;

Barthel, Alexander ;

Kluge, Ralph ;

Stroehl, Dieter .

BIOORGANIC & MEDICINAL CHEMISTRY, 2010, 18 (20) :7252-7259

← 1 2 3 4 5 6 7 8 →