DDR SUBPROJ 4: SYNTHESIS OF N-AMINOTETRAHYDROPYRIDINES AS ANTICANCER

DDR 子项目 4：作为抗癌剂的 N-氨基四氢吡啶的合成

• 批准号: 7715246
• 负责人: KINFE KEN REDDA
• 金额: $ 14.67万
• 依托单位: FLORIDA AGRICULTURAL AND MECHANICAL UNIV
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715246
• 关键词: Animals; Arachidonic Acids; Aspirin; Brain; Colon Carcinoma; Colonic Neoplasms; Colorectal; Computer Retrieval of Information on Scientific Projects Database; Development; Electronics; Enzymes; Esophageal; Funding; Grant; Human; Immune; Inflammation; Institution; Lung; Lung Neoplasms; Malignant - descriptor; Malignant Neoplasms; Mediating; Metabolism; Mind; Non-Steroidal Anti-Inflammatory Agents; PTGS2 gene; Personal Satisfaction; Piroxicam; Property; Prostaglandin-Endoperoxide Synthase; Publishing; Reporting; Research; Research Personnel; Resources; Role; Series; Source; Stomach; Structure; Sulindac; Testing; United States National Institutes of Health; Work; analog; chemotherapeutic agent; cyclooxygenase 1; cyclooxygenase 2

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. The objective of the proposed research is to develop effective chemotherapeutic agents that can be utilized for the treatment of lung and colon cancers. The role of non steroidal anti-inflammatory agents (NSAIDs) such as aspirin, piroxicam, and sulindac in colon cancer has been well-documented in epidemiological and animal studies. Accumulating evidence indicates that the inhibition of colon tumor development by NSAIDs is mediated through the modulation of arachidonic acid metabolism via the cyclooxygenase enzymes, which in turn inhibit immune responsiveness. The increased expression of cyclooxygenase-2 (COX-2) enzyme has been reported to correlate with the malignant changes observed in a variety of human cancers, including colorectal, gastric, esophageal, brain, and lung tumors. With this in mind, it is reasonable to postulate that compounds that induce COX-2 could predipose to cancer or inflammation. Our earlier published work established that the N-aminocarbonyl-1,2,3,6-tetrahydropyridine analogs we synthesized were effective non steroidal anti-inflammatory agents with strong cyclooxygenae-1 (COX-1) and (COX-2) inhibitory activities. The proposed analogs can be tested so that a series of compounds related to the most active analogs could be prepared. Structure activity analysis to study the electronic, steric and lipophilic effects of substituents on the physicochemical properties of the molecule will be carried out.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该研究的目的是开发有效的化疗药物，可用于治疗肺癌和结肠癌。非甾体抗炎药（NSAID）如阿司匹林、吡罗昔康和舒林酸在结肠癌中的作用已在流行病学和动物研究中得到充分证实。越来越多的证据表明，NSAID对结肠肿瘤发展的抑制作用是通过环加氧酶调节花生四烯酸代谢介导的，而环加氧酶反过来又抑制免疫反应。环氧合酶-2（考克斯-2）酶的表达增加已被报道与在多种人类癌症（包括结肠直肠、胃、食管、脑和肺肿瘤）中观察到的恶性变化相关。考虑到这一点，合理的假设是诱导考克斯-2的化合物可能倾向于癌症或炎症。我们早期发表的工作表明，我们合成的N-氨基羰基-1，2，3，6-四氢吡啶类似物是有效的非甾体抗炎药，具有强的环氧合酶-1（考克斯-1）和（考克斯-2）抑制活性。可以测试所提出的类似物，从而可以制备与最具活性的类似物相关的一系列化合物。将进行结构活性分析，以研究取代基对分子物理化学性质的电子、空间和亲脂效应。