MARINE NATURAL PRODUCTS AS ANTI-ANGIOGENIC AND ANTI-INVASIVE AGENTS

海洋天然产品作为抗血管生成和抗侵袭剂

• 批准号: 7719997
• 负责人: KHALID A EL SAYED
• 金额: $ 12.41万
• 依托单位: LOUISIANA STATE UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7719997
• 关键词: Biological Factors; Callyspongia; Cause of Death; Class; Computer Retrieval of Information on Scientific Projects Database; Evaluation; Funding; Future; Goals; Grant; Hydantoins; Institution; Invasive; Malignant Neoplasms; Marines; Porifera; Red Sea; Research; Research Personnel; Resources; Source; United States National Institutes of Health; analog; anticancer activity; computational chemistry; coral; marine natural product; microorganism; model design; molecular modeling; novel; pre-clinical; prototype; scaffold

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. Cancer remains one of the major global causes of death. Marine natural products are enormous resource of highly bioactive compounds. The ultimate goal of this study is to discover and optimize prototype anticancer leads of marine origin. Our research is focused on four different classes of readily available marine natural products. These compounds occur in the Red Sea marine sponges Negombata magnifica, Callyspongia siphonella, Hemimycale arabica, and the soft coral Sarcophyton glaucum. We hypothesized that effective prototypic anticancer latrunculins, sipholanes, hydantoins, and cembranoids can be generated using biocatalysis and semisynthetic approaches. We also hypothesized symbiotic microorganisms associated with the Red Sea sponges N. magnifica and C. siphonella as novel biocatalysts appropriate to enhance the anticancer activity of natural product scaffolds. The specific aims of this study were: 1) optimization of latrunculins, sipholanes, hydantoins, and cembranoids using biocatalytic and rational semisynthetic approaches; 2) application of symbiotic microorganisms associated with N. magnifica, and C. siphonella as potential biocatalysts for bioactive scaffolds; 3) application of computational chemistry and molecular modeling for the design of active semisynthetic analogs; and 4) evaluation of anti-metastatic/anti-invasive activities of the isolated compounds. These compounds showed anti-invasive, anti-migratory, antiproliferative, and HIF-1 inhibitory activities. Future efforts will be focused on preclinical evaluation of few these compounds as potential anti-invasive leads.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 癌症仍然是全球主要死亡原因之一。海洋天然产物是高生物活性化合物的巨大资源。这项研究的最终目标是发现和优化海洋来源的原型抗癌先导化合物。我们的研究重点是四种不同类别的现成海洋天然产品。这些化合物存在于红海海绵 Negombata magnifica、Callyspongia siphonella、Hemimycale arabica 和软珊瑚 Sarcophyton glaucum 中。我们假设可以使用生物催化和半合成方法产生有效的原型抗癌拉特伦库林、西弗兰、乙内酰脲和西松烷类化合物。我们还假设与红海海绵 N. magnifica 和 C. siphonella 相关的共生微生物作为适合增强天然产物支架的抗癌活性的新型生物催化剂。 本研究的具体目的是： 1）使用生物催化和合理的半合成方法优化 latrunculins、sipholanes、hydantoins 和 cembranoids； 2）与N. magnifica和C. siphonella相关的共生微生物作为生物活性支架的潜在生物催化剂的应用； 3）应用计算化学和分子模型设计活性半合成类似物； 4)评估分离化合物的抗转移/抗侵袭活性。这些化合物表现出抗侵袭、抗迁移、抗增殖和 HIF-1 抑制活性。未来的工作将集中于对这些化合物作为潜在抗侵入先导药物的临床前评估。