SORPTION AND BIODEGRADATION OF PHARMACEUTICAL COMPOUNDS IN BIOLOGICAL SYSTEMS

生物系统中药物化合物的吸附和生物降解

• 批准号: 8364216
• 负责人: Willie Frank Harper
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364216
• 关键词: Biodegradation; Biomedical Research; Chemicals; Cleaved cell; Computers; Coupled; Estradiol; Estriol; Estrone; Ethinyl Estradiol; Funding; Grant; High Performance Computing; Hydrophobicity; Laboratory Research; Literature; Metabolic Biotransformation; Metabolic Pathway; Modeling; National Center for Research Resources; Parents; Pathway interactions; Pharmacologic Substance; Principal Investigator; Research; Research Infrastructure; Resources; Self Care; Source; Testing; Toxic effect; United States National Institutes of Health; biological systems; cost; electron density; frontier

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The purpose of this research is to develop a quantitative structural analysis relationship (QSAR) between the toxicity of pharmaceutical compounds and personal care products (PPCPs) and their chemical composition. In the first year of research using the super computer, an organizing principle with which to predict and understand the biotransformation of (PPCPs) was developed. Frontier electron density (FED), coupled with previous laboratory research and literature on the degradation of PPCPs, was used to develop a model for predicting the biotransformation pathways. The focus of this years research is to determine the change in toxicity as a function of biotransformation. The hypothesis is that the toxicity will be related to the hydrophobicity of the parent compounds and their metabolites and that the toxicity will depend on which ring is cleaved first in the metabolic pathway. We are testing this hypothesis for various PPCPs, including Estriol, 17? Ethinylestradiol, Estrone, and 17 ? Estradiol.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其他NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 本研究的目的是建立药物化合物和个人护理产品（PPCPs）的毒性与其化学成分之间的定量结构分析关系（QSAR）。在使用超级计算机进行研究的第一年，开发了预测和理解PPCPs生物转化的组织原则。前线电子密度（FED），加上以前的实验室研究和文献上的降解PPCPs，被用来开发一个模型预测的生物转化途径。今年研究的重点是确定毒性的变化作为生物转化的函数。假设毒性将与母体化合物及其代谢物的疏水性相关，并且毒性将取决于代谢途径中哪个环首先裂解。我们正在测试这一假设的各种PPCPs，包括雌三醇，17？炔雌醇雌酮和17号埃弗里