title: Molecular design of anticancer drug leads based on three-dimensional quantitative structure-activity relationship.
abstract: Heat shock protein 90 (Hsp90) takes part in the developments of several cancers. Novobiocin, a typically C-terminal inhibitor for Hsp90, will probably used as an important anticancer drug in the future. In this work, we explored the valuable information and designed new novobiocin derivatives based on a three-dimensional quantitative structure-activity relationship (3D QSAR). The comparative molecular field analysis and comparative molecular similarity indices analysis models with high predictive capability were established, and their reliabilities are supported by the statistical parameters. Based on the several important influence factors obtained from these models, six new novobiocin derivatives with higher inhibitory activities were designed and confirmed by the molecular simulation with our models, which provide the potential anticancer drug leads for further research.
authors.affiliation: College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, People's Republic of China.
authors.forename: Xiao Yan
authors.initials: XY
authors.lastname: Huang
authors.forename: Zhi Jie
authors.initials: ZJ
authors.lastname: Shan
authors.forename: Hong Lin
authors.initials: HL
authors.lastname: Zhai
authors.forename: Li Na
authors.initials: LN
authors.lastname: Li
authors.forename: Xiao Yun
authors.initials: XY
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D016018:Least-Squares Analysis; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D009675:Novobiocin / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D054852:Small Molecule Libraries; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D054852:Small Molecule Libraries; D009675:Novobiocin