Novel semisynthetic spin-labeled derivatives of podophyllotoxin with cytotoxic and antioxidative activity

被引：21

作者：

Zhang, Jia-Qiang ^{[1
]}

Zhang, Zhi-Wei ^{[1
]}

Hui, Ling ^{[3
]}

Chen, Shi-Wu ^{[1
,2
]}

Tian, Xuan ^{[1
]}

机构：

[1] Lanzhou Univ, State Key Lab Appl Organ Chem, Lanzhou 730000, Peoples R China

[2] Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China

[3] Lanzhou Gen Hosp, Ctr Med Expt, Lanzhou 730050, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 03期

关键词：

Podophyllotoxin; Nitroxides; Antitumor; Antioxidants; BIOLOGICAL EVALUATION; ANTITUMOR-ACTIVITY; DESIGN; ASSAY;

D O I：

10.1016/j.bmcl.2009.12.048

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel spin-labeled podophyllotoxin derivatives were synthesized by reacting the corresponding N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyloxy carbonyl)-amino acids with 4 beta-amino-4'-demethylepipodophyllotoxin. The synthesized derivatives 12a-g were evaluated for the partition coefficients, cytotoxicities in vitro against three tumor cell lines (A-549, HL-60, and RPMI-8226) and antioxidative activities in tissues of SD rats by the TBA method. The vast majority of target compounds have shown superior or comparable activities against A-549, HL-60, and RPMI-8226 compared to VP-16, and they have shown more significant antioxidative activities and superior water solubility than VP-16. (c) 2009 Elsevier Ltd. All rights reserved.

引用

页码：983 / 986

页数：4

共 24 条

[1] Podophyllotoxin [J].

Canel, C ;

Moraes, RM ;

Dayan, FE ;

Ferreira, D .

PHYTOCHEMISTRY, 2000, 54 (02) :115-120

[2] Synthesis and biological evaluation of new selective cytotoxic cyclolignans derived from podophyllotoxin [J].

Castro, MA ;

del Corral, JMM ;

Gordaliza, M ;

García, PA ;

Gómez-Zurita, MA ;

García-Grdvalos, MD ;

de la Iglesia-Vicente, J ;

Gajate, C ;

An, FY ;

Mollinedo, F ;

San Feliciano, A .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (05) :1214-1222

[3] Synthesis and anti-HIV-1 activities of novel podophyllotoxin derivatives [J].

Chen, Shi-Wu ;

Wang, Yun-Hua ;

Jin, Yan ;

Tian, Xuan ;

Zheng, Yong-Tang ;

Luo, Du-Qiang ;

Tu, Yong-Qiang .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (07) :2091-2095

[4] Synthesis of New Conjugates of Modified Podophyllotoxin and Stavudine [J].

Chen, Shi-Wu ;

Xiang, Rong ;

Tian, Xuan .

HELVETICA CHIMICA ACTA, 2009, 92 (08) :1568-1574

[5] Synthesis and biological evaluation of novel conjugates of podophyllotoxin and 5-FU as antineoplastic agents [J].

Chen, Shi-Wu ;

Xiang, Rong ;

Liu, Jian ;

Tian, Xuan .

BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (08) :3111-3117

[6] Synthesis and cytotoxic activity of novel derivatives of 4′-demethylepipodophyllotoxin [J].

Chen, SW ;

Xuan, T ;

Tu, YQ .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (20) :5063-5066

[7] Antitumor agents .163. Three-dimensional quantitative structure-activity relationship study of 4'-O-demethylepipodophyllotoxin analogs using the modified CoMFA/q(2)-GRS approach [J].

Cho, SJ ;

Tropsha, A ;

Suffness, M ;

Cheng, YC ;

Lee, KH .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (07) :1383-1395

[8] Lignoids in insects:: chemical probes for the study of ecdysis, excretion and Trypanosoma cruzi -: triatomine interactions [J].

Garcia, ES ;

Azambuja, P .

TOXICON, 2004, 44 (04) :431-440

[9] Natural products as leads to anticancer drugs [J].

Gordaliza, M. .

CLINICAL & TRANSLATIONAL ONCOLOGY, 2007, 9 (12) :767-776

[10] Synthesis and antineoplastic activity of cyclolignan aldehydes [J].

Gordaliza, M ;

Castro, A ;

del Corral, JM ;

López-Vázquez, L ;

García, PA ;

García-Grávalos, D ;

San Feliciano, A .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2000, 35 (7-8) :691-698

← 1 2 3 →