Linked parallel synthesis and MTT bioassay screening of substituted chalcones

被引：79

作者：

Lawrence, NJ

Rennison, D

McGown, AT

Ducki, S

Gul, LA

Hadfield, JA

Khan, N

机构：

[1] Univ Manchester, Inst Sci & Technol, Dept Chem, Manchester M60 1QD, Lancs, England

[2] Christie Hosp NHS Trust, Paterson Inst Canc Res, CRC, Sect Drug Dev, Manchester M20 4BX, Lancs, England

来源：

JOURNAL OF COMBINATORIAL CHEMISTRY | 2001年 / 3卷 / 05期

关键词：

D O I：

10.1021/cc000075z

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

A 644-membered library of chalcones was prepared by parallel synthesis using the Claisen-Schmidt base-catalyzed aldol condensation of substituted acetophenones and benzaldehydes. The cytotoxicity of these chalcones was conveniently determined upon the crude products directly in 96-well microtiter test plates by the conventional MTT assay. This method revealed seven chalcones Of IC50 less than 1 muM of which 4'-hydroxy-2,4,6,3'-tetramethoxychalcone (5a) was the most active [IC50 (K562), 30 nM]; it causes cell cycle arrest at the G(2)/M point and binds to tubulin at the colchicine binding site.

引用

收藏

页码：421 / 426

页数：6

相关论文

共 40 条

[1] The preparation and properties of an ene-diol. alpha-o-methoxyphenyl-beta-mesitoylacetylene glycol [J].

Barnes, RP ;

Lucas, WM .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1942, 64 :2260-2261

[2]

BELYAEV VF, 1964, J GEN CHEM USSR, V34, P856

[3] SYNTHESIS AND EVALUATION OF STILBENE AND DIHYDROSTILBENE DERIVATIVES AS POTENTIAL ANTICANCER AGENTS THAT INHIBIT TUBULIN POLYMERIZATION [J].

CUSHMAN, M ;

NAGARATHNAM, D ;

GOPAL, D ;

CHAKRABORTI, AK ;

LIN, CM ;

HAMEL, E .

JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (08) :2579-2588

[4]

Dark GG, 1997, CANCER RES, V57, P1829

[5] Potent antimitotic and cell growth inhibitory properties of substituted chalcones [J].

Ducki, S ;

Forrest, R ;

Hadfield, JA ;

Kendall, A ;

Lawrence, NJ ;

McGown, AT ;

Rennison, D .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (09) :1051-1056

[6] Synthesis and cell growth inhibitory properties of substituted (E)-1-phenylbut-1-en-3-ones [J].

Ducki, S ;

Hadfield, JA ;

Hepworth, LA ;

Lawrence, NJ ;

Liu, CY ;

McGown, AT .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (24) :3091-3094

[7]

Edmondson J.M., 1998, METHODS CELL SCI, V11, P15, DOI [10.1007/BF01404408, DOI 10.1007/BF01404408]

[8] CHALCONES - A NEW CLASS OF ANTIMITOTIC AGENTS [J].

EDWARDS, ML ;

STEMERICK, DM ;

SUNKARA, PS .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (07) :1948-1954

[9] The United Kingdom Chemical Database Service [J].

Fletcher, DA ;

McMeeking, RF ;

Parkin, D .

JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 1996, 36 (04) :746-749

[10] In vivo and in vitro evaluation of combretastatin A-4 and its sodium phosphate prodrug [J].

Grosios, K ;

Holwell, SE ;

McGown, AT ;

Pettit, GR ;

Bibby, MC .

BRITISH JOURNAL OF CANCER, 1999, 81 (08) :1318-1327

← 1 2 3 4 →