Cyanobacterial pseudo-natural products for anticancer drug discovery

项目摘要 蓝藻产生的次级代谢产物已被充分证明拥有 有效和选择性的抗癌活性，这导致FDA批准了一种 用于治疗几种霍奇金淋巴瘤的蓝细菌抗体-药物缀合物（ADC） 淋巴瘤尽管这突出了天然产物在药物中的关键作用， 发现，结构支架的新奇在过去的两个月里基本保持稳定 几十年因此，我们的目标是设计和合成一个伪天然产物库 受蓝藻代谢产物的启发，具有良好的抗癌活性， 分子覆盖率。我们的伪天然产品库将开发和描述 一个未知的化学空间，在使用药物的同时， 化学方法，如组合化学和平行合成。我们将 定性和定量表征我们的图书馆使用现代计算， 机器学习和代谢组学技术，将其与天然产品进行比较， FDA批准的药物。这项研究的长期目标是产生一个化学库 富含天然产物支架，偏向于癌症组织用于药物发现 发展先行者的要求我们的主要假设是，我们的图书馆将包含化学 嵌入特权蓝藻结构的生物特性的结构 描述了新的化学空间。

PROJECT ABSTRACT Cyanobacteria produce secondary metabolites have been well-documented to possess potent and selective anticancer activity, which has resulted in FDA approval of a cyanobacterial antibody-drug-conjugate (ADC) for the treatment of several Hodgkin lymphomas. Even though this highlights the critical role of natural products in the drug discovery, the novelty of structural scaffolds has largely remained steady in the last two decades. Therefore, we aim to design and synthesize a pseudo-natural product library inspired by cyanobacterial metabolites with well-described anti-cancer activity to expand their molecular coverage. Our pseudo-natural product library will develop and describe uncharted chemical space that integrates privileged scaffolds while employing medicinal chemistry approaches, such as combinatorial chemistry and parallel synthesis. We will qualitatively and quantitatively characterize our library using modern computational, machine learning and metabolomic techniques, to compare it with natural products and FDA-approved drugs. The long-term goal of this research is to generate a chemical library rich in natural product scaffolds that are biased towards cancer tissue for drug discovery and development. Our main hypothesis is that our library will contain chemical architectures embedded with biological properties of privileged cyanobacterial structures that describe new chemical space.