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.

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。 癌症仍然是全球主要的死亡原因之一。海洋天然产物是具有高生物活性化合物的巨大资源。本研究的最终目标是发现和优化原型抗癌线索的海洋来源。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、Callypongia siphonella、阿拉伯半菌藻和软珊瑚Sarcophyton glaucum中。我们假设，有效的原型抗癌latrunculins，sipholanes，乙内酰脲，西松烷，可以使用生物催化和半合成的方法产生。我们还假设了与红海海绵N. magnifica和C.作为新的生物催化剂，适合于提高天然产物支架的抗癌活性。 本研究的具体目标是：1）利用生物催化和合理半合成方法优化latrunculins、sipholanes、hetoins和cesbranoids; magnifica和C.作为生物活性支架的潜在生物催化剂; 3）应用计算化学和分子模拟设计活性半合成类似物;和4）评价分离的化合物的抗转移/抗侵袭活性。这些化合物显示出抗侵袭、抗迁移、抗增殖和HIF-1抑制活性。未来的努力将集中在临床前评估的几个这些化合物作为潜在的抗侵入性的领导。