title: Synthesis and biological evaluation of analogues of butyrolactone I and molecular model of its interaction with CDK2.
abstract: A series of analogues of butyrolactone I, a natural product isolated from Aspergillus terreus that selectively inhibits the CDK2 and CDK1 kinases and that has been found to exhibit an interesting antiproliferative activity, have been synthesized. Its antitumor activity has been tested. Molecular models of the complex between butyrolactone I and the CDK2 active site have been built using a combination of conformational search and automated docking techniques. The stability of the resulting complexes has been assessed by molecular dynamics simulations and the experimental results obtained for the synthesized analogues are rationalized based on the molecular models.
authors.affiliation: Departamento de CC Químicas, Facultad de CC, Experimentales y de la Salud, Universidad San Pablo CEU, Urb. Montepríncipe, Boadilla del Monte, 28668 Madrid, Spain.
authors.forename: Miguel F
authors.initials: MF
authors.lastname: Braña
authors.forename: M Luisa
authors.initials: ML
authors.lastname: García
authors.forename: Berta
authors.initials: B
authors.lastname: López
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Pascual-Teresa
authors.forename: Ana
authors.initials: A
authors.lastname: Ramos
authors.forename: Jose M
authors.initials: JM
authors.lastname: Pozuelo
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Domínguez
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017434:Protein Structure, Tertiary
chemical_list: D004952:Esters; D047428:Protein Kinase Inhibitors; C082868:butyrolactone I; D015107:4-Butyrolactone