Linked parallel synthesis and MTT bioassay screening of substituted chalcones.
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 IC(50) less than 1 microM of which 4'-hydroxy-2,4,6,3'-tetramethoxychalcone (5a) was the most active [IC(50) (K562), 30 nM]; it causes cell cycle arrest at the G(2)/M point and binds to tubulin at the colchicine binding site.
Lawrence
N J
NJ
Department of Chemistry, University of Manchester Institute of Science and Technology, P.O. Box 88, Manchester, M60 1QD, UK. Lawrencenj1@cardiff.ac.uk
Rennison
D
D
McGown
A T
AT
Ducki
S
S
Gul
L A
LA
Hadfield
J A
JA
Khan
N
N
D000098:Acetophenones / Q000138:chemical synthesis / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002599:Chalcone / Q000138:chemical synthesis* / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015203:Reproducibility of Results; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
D000098:Acetophenones; D000970:Antineoplastic Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D002599:Chalcone; C022616:thiazolyl blue