Asymmetric synthesis and evaluation of α-quaternary chiral lactam derivatives as novel anticancer agents

被引：4

作者：

Lee, Hwanhyuk ^{[1
]}

Hwang, Su Jung ^{[1
]}

Jung, Jisung ^{[1
]}

Hong, Suckchang ^{[2
,3
]}

Lee, Myungmo ^{[2
,3
]}

Park, Hyeung-geun ^{[2
,3
]}

Lee, Hyo-Jong ^{[1
]}

Park, Yohan ^{[1
]}

机构：

[1] Inje Univ, Coll Pharm, Gimhae 621749, Gyeongnam, South Korea

[2] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul 151742, South Korea

[3] Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea

来源：

ARCHIVES OF PHARMACAL RESEARCH | 2014年 / 37卷 / 10期

基金：

新加坡国家研究基金会;

关键词：

alpha-Quaternary chiral lactam; Phase-transfer catalytic alkylation; Colon; Lung; Breast cancers; Anticancer activity; PHASE-TRANSFER CATALYSIS; BETA-LACTAMS; AMINO-ACIDS; INHIBITORS; ESTERS; 5-FLUOROURACIL; ALKYLATION; SUNITINIB; DESIGN;

D O I：

10.1007/s12272-013-0274-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Asymmetric synthesis of alpha-quaternary chiral lactam derivatives as novel anticancer agents and evaluation of their cytotoxic potentials and spectrums are reported. Among the developed lactam derivatives, the most active new compounds (S)-4m and (S)-4n synthesized via asymmetric phase-transfer catalytic alkylation in very high optical yields (98 % ee) show promising in vitro anticancer activities with low micromolar IC50 values against colon, uterus, lung, and breast human cancer cells.

引用

页码：1264 / 1270

页数：7

共 26 条

[1] Selective anticancer activity of β-lactams derived from polyaromatic compound [J].

Banik, Bimal K. ;

Becker, Frederick F. .

MOLECULAR MEDICINE REPORTS, 2010, 3 (02) :315-316

[2] Synthesis of anticancer β-lactams:: mechanism of action [J].

Banik, BK ;

Becker, FF ;

Banik, I .

BIOORGANIC & MEDICINAL CHEMISTRY, 2004, 12 (10) :2523-2528

[3] Property-Based Optimization of Hydroxamate-Based γ-Lactam HDAC Inhibitors to Improve Their Metabolic Stability and Pharmacokinetic Profiles [J].

Choi, Eunhyun ;

Lee, Chulho ;

Cho, Misun ;

Seo, Jeong Jea ;

Yang, Jee Sun ;

Oh, Soo Jin ;

Lee, Kiho ;

Park, Song-Kyu ;

Kim, Hwan Mook ;

Kwon, Ho Jeong ;

Han, Gyoonhee .

JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (23) :10766-10770

[4] Sunitinib: From rational design to clinical efficacy [J].

Chow, Laura Q. M. ;

Eckhardt, S. Gail .

JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (07) :884-896

[5] THE MODE OF ACTION OF 5-FLUOROURACIL AND ITS DERIVATIVES [J].

COHEN, SS ;

FLAKS, JG ;

BARNER, HD ;

LOEB, MR ;

LICHTENSTEIN, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1958, 44 (10) :1004-1012

[6] Novel mammalian cell cycle inhibitors, spirotryprostatins A and B, produced by Aspergillus fumigatus, which inhibit mammalian cell cycle at G2/M phase [J].

Cui, CB ;

Kakeya, H ;

Osada, H .

TETRAHEDRON, 1996, 52 (39) :12651-12666

[7] Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial [J].

Demetri, George D. ;

van Oosterom, Allan T. ;

Garrett, Christopher R. ;

Blackstein, Martin E. ;

Shah, Manisha H. ;

Verweij, Jaap ;

McArthur, Grant ;

Judson, Ian R. ;

Heinrich, Michael C. ;

Morgan, Jeffrey A. ;

Desai, Jayesh ;

D Fletcher, Christopher ;

George, Suzanne ;

Bello, Carlo L. ;

Huang, Xin ;

Baum, Charles M. ;

Casali, Paolo G. .

LANCET, 2006, 368 (9544) :1329-1338

[8] Pyrrolidinyl-spirooxindole natural products as inspirations for the development of potential therapeutic agents [J].

Galliford, Chris V. ;

Scheidt, Karl A. .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2007, 46 (46) :8748-8758

[9] Recent development and application of chiral phase-transfer catalysts [J].

Hashimoto, Takuya ;

Maruoka, Keiji .

CHEMICAL REVIEWS, 2007, 107 (12) :5656-5682

[10] Cancer statistics, 2008 [J].

Jemal, Ahmedin ;

Siegel, Rebecca ;

Ward, Elizabeth ;

Hao, Yongping ;

Xu, Jiaquan ;

Murray, Taylor ;

Thun, Michael J. .

CA-A CANCER JOURNAL FOR CLINICIANS, 2008, 58 (02) :71-96

← 1 2 3 →