Acid-catalyzed synthesis of 10-substituted triazolyl artemisinins and their growth inhibitory activity against various cancer cells

被引：38

作者：

Oh, Sangtae ^{[2
]}

Shin, Woon-Seob ^{[3
]}

Ham, Jungyeob ^{[1
]}

Lee, Seokjoon ^{[2
]}

机构：

[1] Korea Inst Sci & Technol, Gangneung Inst, Kangnung 210340, South Korea

[2] Kwandong Univ, Coll Med, Dept Basic Sci, Kangnung 210701, South Korea

[3] Kwandong Univ, Coll Med, Dept Microbiol, Kangnung 210701, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 14期

基金：

新加坡国家研究基金会;

关键词：

Artemisinin; Triazoyl artemisinin; Anticancer; Diastereomer; Regioisomer; SOLUBLE DIHYDROARTEMISININ DERIVATIVES; ANTIMALARIAL ACTIVITY; DIFLUOROMETHYLENE KETONES; ARTEETHER; TOXICITY; DRUG;

D O I：

10.1016/j.bmcl.2010.05.074

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A diastereomeric and regioisomeric library of 10-substituted triazolyl artemisinin compounds (6a-6h, 7a-7h, and 8a-8h) with a potent growth inhibitory activities against various cancer cell lines was established. These compounds were synthesized by a reaction with dihydroartemisinin (2) and various substituted triazoles (5a-5h) in methylene chloride using a BF(3)Et(2)O catalyst. Most of the compounds exhibited a strong potency in the submicromolar range, and, in particular, 6f, 7f, and 8f, which have a pentylphenyltriazole moiety, proved to be promising candidates for preclinical trials. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：4112 / 4115

页数：4

共 13 条

[1] NEUROTOXICITY IN ANIMALS DUE TO ARTEETHER AND ARTEMETHER [J].

BREWER, TG ;

PEGGINS, JO ;

GRATE, SJ ;

PETRAS, JM ;

LEVINE, BS ;

WEINA, PJ ;

SWEARENGEN, J ;

HEIFFER, MH ;

SCHUSTER, BG .

TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, 1994, 88 :33-36

[2] Synthesis of 10-substituted triazolyl artemisinins possessing anticancer activity via Huisgen 1,3-dipolar cylcoaddition [J].

Cho, Sungsik ;

Oh, Sangtae ;

Um, Yumi ;

Jung, Ji-Hee ;

Ham, Jungyeob ;

Shin, Woon-Seob ;

Lee, Seokjoon .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (02) :382-385

[3] Fluoro artemisinins:: Difluoromethylene ketones [J].

Chorki, F ;

Grellepois, F ;

Crousse, B ;

Ourévitch, M ;

Bonnet-Delpon, D ;

Bégué, JP .

JOURNAL OF ORGANIC CHEMISTRY, 2001, 66 (23) :7858-7863

[4] C-10-fluorinated derivatives of dihydroartemisinin:: difluoromethylene ketones [J].

Chorki, F ;

Crousse, B ;

Bonnet-Delpon, D ;

Bégué, JP ;

Brigaud, T ;

Portella, C .

TETRAHEDRON LETTERS, 2001, 42 (08) :1487-1489

[5] Behavioral and neural toxicity of the artemisinin antimalarial, arteether, but not artesunate and artelinate, in rats [J].

Genovese, RE ;

Newman, DB ;

Brewer, TG .

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 2000, 67 (01) :37-44

[6] Copper-catalyzed synthesis of N-unsubstituted 1,2,3-triazoles from nonactivated terminal alkynes [J].

Jin, T ;

Kamijo, S ;

Yamamoto, Y .

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2004, 2004 (18) :3789-3791

[7] QINGHAOSU (ARTEMISININ) - AN ANTIMALARIAL DRUG FROM CHINA [J].

KLAYMAN, DL .

SCIENCE, 1985, 228 (4703) :1049-1055

[8] A simple synthesis of C-10 substituted deoxoartemisinin and 9-epi-deoxoartemisinin with various organozinc reagents [J].

Lee, S ;

Oh, S .

TETRAHEDRON LETTERS, 2002, 43 (16) :2891-2894

[9] Artemisinin, promising lead natural product for various drug developments [J].

Lee, Seokjoon .

MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2007, 7 (04) :411-422

[10] ANTIMALARIAL ACTIVITY OF NEW DIHYDROARTEMISININ DERIVATIVES .6. ALPHA-ALKYLBENZYLIC ETHERS [J].

LIN, AJ ;

MILLER, RE .

JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (05) :764-770

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