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Scalable synthesis enabling multilevel bio-evaluations of natural products for discovery of lead compounds.


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.

SUBMITTER: Zhu L 

PROVIDER: S-EPMC5876371 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Scalable synthesis enabling multilevel bio-evaluations of natural products for discovery of lead compounds.

Zhu Lizhi L   Ma Wenjing W   Zhang Mengxun M   Lee Magnolia Muk-Lan MM   Wong Wing-Yan WY   Chan Brandon Dow BD   Yang Qianqian Q   Wong Wing-Tak WT   Tai William Chi-Shing WC   Lee Chi-Sing CS  

Nature communications 20180329 1


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 c  ...[more]

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