title: Synthesis of 5-deazaflavin derivatives and their activation of p53 in cells.
abstract: A family of 5-deazaflavin derivatives has been synthesised using a two-step convergent strategy. The biological activity of these compounds was evaluated in cells, by assessing their ability to stabilize and activate p53. These compounds may act as low molecular weight inhibitors of the E3 activity of HMD2 in tumours that retain wild-type p53. Importantly, we have demonstrated that the nitro group present in all three of the original lead compounds [1-3 (HL198C-E)] is not essential for observation of this biological activity.
authors.affiliation: WestCHEM, Department of Chemistry, The Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Wilson
authors.forename: Graham
authors.initials: G
authors.lastname: Henderson
authors.forename: Fiona
authors.initials: F
authors.lastname: Black
authors.forename: Andrew
authors.initials: A
authors.lastname: Sutherland
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ludwig
authors.forename: Karen H
authors.initials: KH
authors.lastname: Vousden
authors.forename: David J
authors.initials: DJ
authors.lastname: Robins
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D005415:Flavins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D015394:Molecular Structure; D008970:Molecular Weight; D051736:Proto-Oncogene Proteins c-mdm2 / Q000187:drug effects / Q000502:physiology; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects* / Q000378:metabolism
chemical_list: D005415:Flavins; D016159:Tumor Suppressor Protein p53; C019319:5-deazaflavin; D004317:Doxorubicin; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2