Abstract

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.

Details

Title
Scalable synthesis enabling multilevel bio-evaluations of natural products for discovery of lead compounds
Author
Zhu, Lizhi 1 ; Ma, Wenjing 2 ; Zhang, Mengxun 2 ; Magnolia Muk-Lan Lee 3 ; Wing-Yan, Wong 3 ; Brandon Dow Chan 3   VIAFID ORCID Logo  ; Yang, Qianqian 2 ; Wing-Tak Wong 4 ; Tai, William Chi-Shing 5 ; Chi-Sing, Lee 2   VIAFID ORCID Logo 

 Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China; Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Hong Kong, China 
 Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China 
 Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Hong Kong, China 
 Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Hong Kong, China; State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute of The Hong Kong Polytechnic University, Shenzhen 518057, China; State Key Laboratory of Chirosciences, Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Hong Kong, China 
 Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Hong Kong, China; State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute of The Hong Kong Polytechnic University, Shenzhen 518057, China 
Pages
1-10
Publication year
2018
Publication date
Mar 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2019797571
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.