Cytochrome P450 1 enzyme inhibition and anticancer potential of chromene amides from Amyris plumieri

被引：23

作者：

Badal, S. ^{[1
]}

Williams, S. A. ^{[2
]}

Huang, G. ^{[3
]}

Francis, S. ^{[1
]}

Vendantam, P. ^{[3
]}

Dunbar, O. ^{[1
]}

Jacobs, H. ^{[2
]}

Tzeng, T. J. ^{[3
]}

Gangemi, J. ^{[3
]}

Delgoda, R. ^{[1
]}

机构：

[1] Univ W Indies, Fac Pure & Appl Sci, Nat Prod Inst, Mona, Jamaica

[2] Univ W Indies, Fac Pure & Appl Sci, Dept Chem, Mona, Jamaica

[3] Clemson Univ, Dept Biol Sci, Clemson, SC 29634 USA

来源：

FITOTERAPIA | 2011年 / 82卷 / 02期

关键词：

Anticancer; CYP450; Chemoprotection; Chemoprevention; Natural products; Jamaica; IN-VITRO; CYP1A1; EXPRESSION; ACTIVATION; P450;

D O I：

10.1016/j.fitote.2010.10.003

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Cytochrome P450 (CYP) enzyme inhibitory properties of six chromenylated amide compounds (CAs) from Amyris plumieri are described. Inhibition of CYP microsomes (CYP1A1, CYP1A2, CYP1B1, CYP2D6, CYP3A4 and CYP2C19) was monitored using a fluorescent assay. Potent inhibition was found against CYP1A1 with IC50 and K-i for CA1 (acetamide), being the lowest at 1.547+/-1.0 mu M and 0.37 mu M respectively, displaying non-competitive kinetics. The selectivity for CYP1A1 was increased in CA3 (butanamide), which also exhibited cytotoxicity against breast cancer cells, MCF7 with an IC50 of 47.46+/-1.62 mu M. Structure-activity relationship studies provide insight at a molecular level for CAs with implications in chemoprevention and chemotherapy. (C) 2010 Elsevier B.V. All rights reserved.

引用

页码：230 / 236

页数：7

共 31 条

[1]

Aggarwal BB, 2003, ANTICANCER RES, V23, P363

[2]

Badal S, 2008, PROCEEDINGS OF THE 17TH INTERNATIONAL SYMPOSIUM ON MICROSOMES AND DRUG OXIDATIONS, P63

[3] Cytochrome P450 CYP1B1 determines susceptibility to 7,12-dimethylbenz[a]anthracene-induced lymphomas [J].

Buters, JTM ;

Sakai, S ;

Richter, T ;

Pineau, T ;

Alexander, DL ;

Savas, U ;

Doehmer, J ;

Ward, JM ;

Jefcoate, CR ;

Gonzalez, FJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (05) :1977-1982

[4]

CALI J, SCREEN CYP450 INHIBI

[5] Fetal Mouse Cyp1b1 and Transplacental Carcinogenesis from Maternal Exposure to Dibenzo(a,l)pyrene [J].

Castro, David J. ;

Baird, William M. ;

Pereira, Clifford B. ;

Giovanini, Jack ;

Loehr, Christiane V. ;

Fischer, Kay A. ;

Yu, Zhen ;

Gonzalez, Frank J. ;

Krueger, Sharon K. ;

Williams, David E. .

CANCER PREVENTION RESEARCH, 2008, 1 (02) :128-134

[6] The flavonoid galangin is an inhibitor of CYP1A1 activity and an agonist/antagonist of the aryl hydrocarbon receptor [J].

Ciolino, HP ;

Yeh, GC .

BRITISH JOURNAL OF CANCER, 1999, 79 (9-10) :1340-1346

[7] Microtiter plate assays for inhibition of human, drug-metabolizing cytochromes P450 [J].

Crespi, CL ;

Miller, VP ;

Penman, BW .

ANALYTICAL BIOCHEMISTRY, 1997, 248 (01) :188-190

[8]

FORTI R, 2008, DRUG METAB DISPOS, V36, P523

[9]

FUENTE GDL, 1991, PHYTOCHEMISTRY, V30, P2677

[10] Mechanism-based in vitro screening of potential cancer chemopreventive agents [J].

Gerhäuser, C ;

Klimo, K ;

Heiss, E ;

Neumann, I ;

Gamal-Eldeen, A ;

Knauft, J ;

Liu, GY ;

Sitthimonchai, S ;

Frank, N .

MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2003, 523 :163-172

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