Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen University Town, Xili, Shenzhen 518055, China.
Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Hong Kong, China.
Nat Commun. 2018 Mar 29;9(1):1283. doi: 10.1038/s41467-018-03546-9.
Challenges in the development of anti-cancer chemotherapeutics continue to exist, particularly with respect to adverse effects and development of resistance, underlining the need for novel drugs with good safety profiles. Natural products have proven to be a fertile ground for exploitation, and development of anti-cancer drugs from structurally complex natural products holds promise. Unfortunately, this approach is often hindered by low isolation yields and limited information from preliminary cell-based assays. Here we report a concise and scalable synthesis of a series of low-abundance Isodon diterpenoids (a large class of natural products with over 1000 members isolated from the herbs of genus Isodon, which are well-known folk medicines for the treatment of inflammation and cancer), including eriocalyxin B, neolaxiflorin L and xerophilusin I. These scalable syntheses enable multilevel bio-evaluation of the natural products, in which we identify neolaxiflorin L as a promising anti-cancer drug candidate.
抗癌化学疗法的发展仍然存在挑战，特别是在不良反应和耐药性方面，这凸显了对具有良好安全性的新型药物的需求。天然产物已被证明是一个富有成效的开发领域，从结构复杂的天然产物中开发抗癌药物具有广阔的前景。不幸的是，这种方法通常受到低分离产率和初步基于细胞的测定中有限信息的限制。在这里，我们报道了一系列低丰度的冬凌草二萜（一类从冬凌草属植物中分离出的具有 1000 多种成员的天然产物，该属植物是治疗炎症和癌症的民间常用药）的简洁和可扩展的合成方法，包括冬凌草乙素、新冬凌草甲素和瑞香素 I。这些可扩展的合成方法使天然产物的多层次生物评估成为可能，我们从中鉴定出新冬凌草甲素 L 是一种很有前途的抗癌药物候选物。
