Combretastatin-like chalcones as inhibitors of microtubule polymerisation. Part 2: Structure-based discovery of alpha-aryl chalcones.

2.50
Hdl Handle:
http://hdl.handle.net/10541/109326
Title:
Combretastatin-like chalcones as inhibitors of microtubule polymerisation. Part 2: Structure-based discovery of alpha-aryl chalcones.
Authors:
Ducki, Sylvie W; Mackenzie, Grant; Greedy, Ben; Armitage, Simon; Chabert, Jérémie Fournier Dit; Bennett, Elizabeth; Nettles, Jim; Snyder, James P; Lawrence, Nicholas J
Abstract:
Tubulin is an important molecular target in cancer chemotherapy. Antimitotic agents able to bind to the protein are currently under study, commonly used in the clinic to treat a variety of cancers and/or exploited as probes to investigate the protein's structure and function. Here we report the binding modes for a series of colchicinoids, combretastatin A4 and chalcones established from docking studies carried out on the structure of tubulin in complex with colchicine. The proposed models, in agreement with published biochemical data, show that combretastatin A4 binds to the colchicine site of beta-tubulin and that chalcones assume an orientation similar to that of podophyllotoxin. The models can be used to design a new class of podophyllotoxin mimics, the alpha-aryl chalcones, capable of binding to the colchicine-binding site of beta-tubulin with higher affinity.
Affiliation:
Department of Chemistry, UMIST, Manchester M60 1QD, UK. Sylvie.DUCKI@univ-bpclermont.fr
Citation:
Combretastatin-like chalcones as inhibitors of microtubule polymerisation. Part 2: Structure-based discovery of alpha-aryl chalcones. 2009, 17 (22):7711-22 Bioorg. Med. Chem.
Journal:
Bioorganic & Medicinal Chemistry
Issue Date:
15-Nov-2009
URI:
http://hdl.handle.net/10541/109326
DOI:
10.1016/j.bmc.2009.09.044
PubMed ID:
19837594
Type:
Article
Language:
en
ISSN:
1464-3391
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorDucki, Sylvie Wen
dc.contributor.authorMackenzie, Granten
dc.contributor.authorGreedy, Benen
dc.contributor.authorArmitage, Simonen
dc.contributor.authorChabert, Jérémie Fournier Diten
dc.contributor.authorBennett, Elizabethen
dc.contributor.authorNettles, Jimen
dc.contributor.authorSnyder, James Pen
dc.contributor.authorLawrence, Nicholas Jen
dc.date.accessioned2010-08-09T14:52:45Z-
dc.date.available2010-08-09T14:52:45Z-
dc.date.issued2009-11-15-
dc.identifier.citationCombretastatin-like chalcones as inhibitors of microtubule polymerisation. Part 2: Structure-based discovery of alpha-aryl chalcones. 2009, 17 (22):7711-22 Bioorg. Med. Chem.en
dc.identifier.issn1464-3391-
dc.identifier.pmid19837594-
dc.identifier.doi10.1016/j.bmc.2009.09.044-
dc.identifier.urihttp://hdl.handle.net/10541/109326-
dc.description.abstractTubulin is an important molecular target in cancer chemotherapy. Antimitotic agents able to bind to the protein are currently under study, commonly used in the clinic to treat a variety of cancers and/or exploited as probes to investigate the protein's structure and function. Here we report the binding modes for a series of colchicinoids, combretastatin A4 and chalcones established from docking studies carried out on the structure of tubulin in complex with colchicine. The proposed models, in agreement with published biochemical data, show that combretastatin A4 binds to the colchicine site of beta-tubulin and that chalcones assume an orientation similar to that of podophyllotoxin. The models can be used to design a new class of podophyllotoxin mimics, the alpha-aryl chalcones, capable of binding to the colchicine-binding site of beta-tubulin with higher affinity.en
dc.language.isoenen
dc.subject.meshAlgorithms-
dc.subject.meshBibenzyls-
dc.subject.meshBinding Sites-
dc.subject.meshCell Line-
dc.subject.meshChalcones-
dc.subject.meshColchicine-
dc.subject.meshDrug Discovery-
dc.subject.meshHumans-
dc.subject.meshHydrocarbons, Cyclic-
dc.subject.meshMicrotubules-
dc.subject.meshStructure-Activity Relationship-
dc.subject.meshTubulin Modulators-
dc.titleCombretastatin-like chalcones as inhibitors of microtubule polymerisation. Part 2: Structure-based discovery of alpha-aryl chalcones.en
dc.typeArticleen
dc.contributor.departmentDepartment of Chemistry, UMIST, Manchester M60 1QD, UK. Sylvie.DUCKI@univ-bpclermont.fren
dc.identifier.journalBioorganic & Medicinal Chemistryen

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