Synthesis of novel α-santonin derivatives as potential cytotoxic agents

被引：29

作者：

Arantes, Francisco F. P. ^{[1
]}

Barbosa, Luiz C. A. ^{[1
]}

Maltha, Celia R. A. ^{[1
]}

Demuner, Antonio J. ^{[1
]}

da Costa, Patricia Marcal ^{[2
]}

Ferreira, Jose R. O. ^{[2
]}

Costa-Lotufo, Leticia V. ^{[2
]}

Moraes, Manoel O. ^{[2
]}

Pessoa, Claudia ^{[2
]}

机构：

[1] Univ Fed Vicosa, Dept Chem, BR-36570000 Vicosa, MG, Brazil

[2] Univ Fed Ceara, Dept Physiol & Pharmacol, BR-60431970 Fortaleza, CE, Brazil

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 45卷 / 12期

关键词：

Parishin A synthesis; Sesquiterpene lactones; alpha-methylene-gamma-lactone; Endoperoxide bridge; Cytotoxicity; SIYEKUCAI IXERIS-CHINENSIS; SESQUITERPENE LACTONES; PSEUDOGUAIANOLIDE SKELETON; PHYTOTOXIC ACTIVITY; ANTITUMOR-ACTIVITY; CONCISE SYNTHESIS; GAMMA-LACTONES; GROWTH; APOPTOSIS; CELLS;

D O I：

10.1016/j.ejmech.2010.10.003

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

Ten novel alpha-santonin derivatives have been synthesized as cytotoxic agents. The in vitro antitumor activity of these compounds has been evaluated against cancer cells lines. Structure-activity relationships indicate that alpha-methylene-gamma-lactone and endoperoxide functionalities play important roles in conferring cytotoxicity. The compounds 2-4, possessing the alpha-methylene-gamma-lactone group showed IC50 values between 5.70 and 16.40 mu M. Mixture of isomers 5 and 6, with the alpha-methylene-gamma-lactone and endoperoxide functionalities, displayed the greatest activity, with IC50 values between 1.45 and 4.35 mu M. The biological assays conducted with normal cells revealed that the compounds 2, 5 and 6 are selective against cancer cells lines tested. Bioactive lactones described herein and in our previous report did not cause disruption of the cell membrane in mouse erythrocytes. (C) 2010 Elsevier Masson SAS. All rights reserved.

引用

页码：6045 / 6051

页数：7

共 46 条

[1]

A NEW RAPID AND SIMPLE NONRADIOACTIVE ASSAY TO MONITOR AND DETERMINE THE PROLIFERATION OF LYMPHOCYTES - AN ALTERNATIVE TO [H-3] THYMIDINE INCORPORATION ASSAY [J].

AHMED, SA ;

GOGAL, RM ;

WALSH, JE .

JOURNAL OF IMMUNOLOGICAL METHODS, 1994, 170 (02) :211-224

[2]

DRUG-BINDING TO HUMAN ERYTHROCYTES IN THE PROCESS OF IONIC DRUG-INDUCED HEMOLYSIS - FLOW MICROCALORIMETRIC APPROACHES [J].

AKI, H ;

YAMAMOTO, M .

BIOCHEMICAL PHARMACOLOGY, 1991, 41 (01) :133-138

[3]

SYNTHESIS AND EVALUATION OF THE PHYTOTOXIC ACTIVITY OF α-SANTONIN DERIVATIVES [J].

Alvarenga, Elson S. ;

Barbosa, Luiz C. A. ;

Saliba, William A. ;

Arantes, Francisco F. P. ;

Demuner, Antonio J. ;

Silva, Antonio A. .

QUIMICA NOVA, 2009, 32 (02) :401-406

[4]

[Anonymous], 1991, DICT TERPENOIDS

[5]

Synthesis and cytotoxic activity of α-santonin derivatives [J].

Arantes, Francisco F. P. ;

Barbosa, Luiz C. A. ;

Alvarenga, Elson S. ;

Demuner, Antonio J. ;

Bezerra, Daniel P. ;

Ferreira, Jose R. O. ;

Costa-Lotufo, Leticia V. ;

Pessoa, Claudia ;

Moraes, Manoel O. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2009, 44 (09) :3739-3745

[6]

Barbosa LCA, 1997, J BRAZIL CHEM SOC, V8, P19

[7]

BARBOSA LCD, 1992, J CHEM SOC PERK T 1, P337

[8]

Barbosa LCD, 2004, Z NATURFORSCH C, V59, P803

[9]

Synthesis and phytotoxic activity evaluation of lactone derivatives of 2,4-dimethyl-8-oxabicyclo[3.2.1]-oct-6-en-3-one. [J].

Barbosa, LCD ;

Maltha, CRA ;

Borges, EEL .

QUIMICA NOVA, 2002, 25 (02) :203-208

[10]

BARBOSA LCD, 1990, J CHEM SOC PERK T 1, P177

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