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Biological Studies of alpha-Hydroxytropolones

α-羟基托酚酮的生物学研究

基本信息

批准号：
9271213
负责人：
Ryan Murelli
金额：
$ 39.25万
依托单位：
BROOKLYN COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9271213
关键词：
Adverse effects Animal Model Antimalarials Antiviral Agents Bacterial Infections Binding Biological Biological Assay Bipolar Disorder Chemicals Chemistry Clinical Collaborations Data Development Disease Evaluation Funding Goals Grant HIV Heart Diseases Hepatitis B Herpesvirus 1 International Knowledge Lead Malaria Medical Medicine Methodology Methods Mutagenesis Natural Products Oxygen Positioning Attribute Proteomics Public Health Publications RNA-Directed DNA Polymerase Research Resources Ribonuclease H Route Saints Science Series Simplexvirus Structure Study models Testing Therapeutic Therapeutic Agents Universities anti-hepatitis B anticancer activity base career clinical candidate college computational chemistry cycloaddition cytotoxic cytotoxicity design drug development experimental study human disease inhibitor/antagonist insight medical schools melanoma metalloenzyme novel pharmacophore programs public health relevance symposium therapeutic development

项目摘要

DESCRIPTION (provided by applicant): -Hydroxytropolones are promising pharmacophores for therapeutic development. However, structure-function studies on the molecules have been hampered due to a scarcity of synthetic methods available to access them. The following research will leverage a newly established oxidopyrylium cycloaddition/ring-opening strategy in a series of biological studies on a-hydroxytropolones, and expand the methodology to include a promising subclass of the molecules. Specifically, a computational chemistry-assisted structure-function study will be carried out toward a potent and selective a-hydroxytropolone-based HIV RT RNase H inhibitor. These compounds will also be tested for their antiviral activity for Hepatitis B and Herpes Simplex Virus 1 and 2. New chemical probes will also be synthesized for use in proteomic studies for studying a-hydroxytropolone cytotoxicity. Finally, the chemistry will be expanded to include 3, 7-dihydroxytropolones, which have shown promising cellular antiviral activity for HIV, and have demonstrated activity in animal model studies for malaria and melanoma comparable to current therapeutic agents. The molecules will be tested for their antiviral activity in preliminary structure-function studies against HIV, Hepatitis B and Herpes Simplex Virus. The research proposed is thus a critical step in what is anticipated to be a long-term research program aimed at thoroughly evaluating the therapeutic potential of -hydroxytropolones, with a major goal being the establishment of a new platform for drug development.