Synthesis and anticancer activity of heteroaromatic linked 4β-amido podophyllotoxins as apoptotic inducing agents

被引：33

作者：

Kamal, Ahmed ^{[1
]}

Tamboli, Jaki R. ^{[1
]}

Vishnuvardhan, M. V. P. S. ^{[2
]}

Adil, S. F. ^{[3
]}

Nayak, V. Lakshma ^{[2
]}

Ramakrishna, S. ^{[2
]}

机构：

[1] Indian Inst Chem Technol, CSIR, Div Organ Chem, Hyderabad 500007, Andhra Pradesh, India

[2] Indian Inst Chem Technol, CSIR, Div Pharmacol, Hyderabad 500007, Andhra Pradesh, India

[3] King Saud Univ, Coll Sci, Dept Chem, Riyadh 11451, Saudi Arabia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 01期

关键词：

Podophyllotoxin; Anticancer activity; Cell cycle analysis; Caspase-3; Apoptosis; DNA TOPOISOMERASE-II; CYCLIN-DEPENDENT KINASE; LUNG-CANCER CELLS; ANTITUMOR AGENTS; POTENT INHIBITORS; BIOLOGICAL EVALUATION; ANTIPROLIFERATIVE ACTIVITY; DERIVATIVES; ANALOGS; DESIGN;

D O I：

10.1016/j.bmcl.2012.10.099

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of different heteroaromatic linked 4 beta-amidopodophyllotoxin conjugates (16a-i, 17a-i and 18a-d) were synthesized and evaluated for anticancer activity against five human cancer cell lines. Among the series, one of the compound 17g showed significant antiproliferative activity in A549 (lung cancer) cell line. Flow cytometric analysis showed that 17g arrested the cell cycle in the G2/M phase leading to caspase-3 dependent apoptotic cell death. Further, Hoechst 33258 staining and DNA fragmentation assay also suggests that 17g induces cell death by apoptosis. (c) 2012 Elsevier Ltd. All rights reserved.

引用

页码：273 / 280

页数：8

共 53 条

[1] ETOPOSIDE - CURRENT STATUS AND FUTURE PERSPECTIVES IN THE MANAGEMENT OF MALIGNANT NEOPLASMS [J].

BELANI, CP ;

DOYLE, LA ;

AISNER, J .

CANCER CHEMOTHERAPY AND PHARMACOLOGY, 1994, 34 :S118-S126

[2] FADROZOLE HYDROCHLORIDE - A POTENT, SELECTIVE, NONSTEROIDAL INHIBITOR OF AROMATASE FOR THE TREATMENT OF ESTROGEN-DEPENDENT DISEASE [J].

BROWNE, LJ ;

GUDE, C ;

RODRIGUEZ, H ;

STEELE, RE ;

BHATNAGER, A .

JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (02) :725-736

[3] Podophyllotoxin [J].

Canel, C ;

Moraes, RM ;

Dayan, FE ;

Ferreira, D .

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

[4]

Chen Y, 2005, ANTICANCER RES, V25, P4203

[5] 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

[6] Synthesis of furopyrazole analogs of 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) as novel anti-leukemia agents [J].

Chou, Li-Chen ;

Huang, Li-Jiau ;

Yang, Jai-Sing ;

Lee, Fang-Yu ;

Teng, Che-Ming ;

Kuo, Sheng-Chu .

BIOORGANIC & MEDICINAL CHEMISTRY, 2007, 15 (04) :1732-1740

[7] Synthesis and antiproliferative activity of triazenoindazoles and triazenopyrazoles: a comparative study [J].

Daidone, G ;

Raffa, D ;

Maggio, B ;

Raimondi, MV ;

Plescia, F ;

Schillaci, D .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2004, 39 (03) :219-224

[8]

Daidone Giuseppe, 2004, Farmaco (Lausanne), V59, P413, DOI 10.1016/j.farmac.2004.01.016

[9] Regioselective synthesis and antitumor screening of some novel N-phenylpyrazole derivatives [J].

Farag, Ahmad M. ;

Mayhoub, Abdelrahman S. ;

Barakat, Saber E. ;

Bayomi, Ashraf H. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (02) :881-889

[10]

Gordaliza M., 1811, CURR PHARM DESIGN, V2000, P6

← 1 2 3 4 5 6 →