权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

SYNTHESIS & PHARMACOLOGICAL EVAL OF POTENTIAL ANTI-CANCER & ANTI MICROBIAL AGENT

合成

基本信息

批准号：
7959139
负责人：
John S Cooperwood
金额：
$ 11.73万
依托单位：
FLORIDA AGRICULTURAL AND MECHANICAL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2010-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7959139
关键词：
4-Hydroxy-Tamoxifen Adjuvant Antibiotics Bacteria Breast Cancer Cell Breast Cancer Treatment Chalcone Chalcones Characteristics Collaborations Computer Retrieval of Information on Scientific Projects Database Disease Drug Delivery Systems Early Diagnosis Electronics Estradiol Estrogen Receptors Estrogen receptor positive Estrogens Ethers Flavonoids Funding Goals Grant Growth Incidence Individual Infection Institution Knowledge Lead MCF7 cell Malignant Neoplasms Molecular Models Mutate Nosocomial Infections Pharmaceutical Preparations Research Research Personnel Research Project Grants Resources Side Source Staphylococcus aureus State Interests Steroids Structure Testing United States National Institutes of Health Vaccines Work abstracting antimicrobial drug base cytotoxicity design drug candidate forging hormone therapy hydroxyl group improved interest malignant breast neoplasm methicillin resistant Staphylococcus aureus molecular modeling pathogen receptor success

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ABSTRACT This research project forges collaborations between a junior investigator (Cooperwood) and senior investigators (Du, Redda and Ablordeppey) who have vast knowledge in research. While some success in the treatment of breast cancer have been attained in the recent years through early detection and adjuvant systemic treatment, the incidence of this disease has steadily been on the incline. Endocrine therapy has been proven to be effective against estrogen receptor (ER) positive breast cancer through antagonism of estrogen at its receptor. We plan to target the ER using steroidal base compounds and flavonoids. We have several compounds, which have been designed and synthesized with inhibitory activity against MCF-7 breast cancer cells similar to that 4-hydroxytamoxifen. Another drug targeted disease state of interest is MRSA infections. Drs. Cooperwood, Du and Ablordeppey are involved in research concerning design of potential drugs for the treatment of MRSA and other infections. Among the major pathogens responsible for nosocomial infections is Staphylococcus aureus. Antibiotics have become less effective against S. aureus because the bacteria mutate to resist current treatments. While attempts to obtain vaccines are in the works, there is a need to develop new drugs against S. aureus, and more specifically against MRSA. Hypotheses: The design and synthesis of anti-breast cancer agents are based upon our FlexX molecular model. All of test compounds with MCF-7 inhibitory growth activity have rigid structures (steroids mentioned in preliminary studies) bearing two hydroxyl groups with a separation distance similar to than of estradiol with one hydroxyl group forming an alkylamino ether. We conceptualize that it may be possible to improve MCF-7 inhibitory growth activity by extension of alkylamino side chain. Furthermore, our FlexX molecular model strongly suggests that these concepts can be applied to other rigid structures such as flavonoids and chalcones. The design and synthesis of anti-Methicillin Resistant Staphylococcus aureus (MRSA) bacteria agents are based upon previously synthesized compounds that displayed activity. We conceptualize that by changing the electronic and hydrophobic characteristic of substituents on the phenyl portion of N-alkyl 3-Phenylthioquinolinium will improve potency and reduce cytotoxicity. The goals of this pilot are to design synthesis and develop drug candidates with activities against breast cancer and anti-MRSA agents. To achieve these goals, we will elicit the collaboration of individuals who have an invested interest in various disease states to carry out the specific aims which are (1) to design, synthesize and evaluate the pharmacological activities of compounds as potential anti-breast cancer, anti-Methicillin-Resistant Staphylococcus aureus (MRSA) and (2) lead compound(s) optimization based upon pharmacological activities and molecular modeling studies.

这个子项目是众多研究子项目之一