TY - JOUR
T1 - Scalable synthesis enabling multilevel bio-evaluations of natural products for discovery of lead compounds
AU - Zhu, Lizhi
AU - Ma, Wenjing
AU - Zhang, Mengxun
AU - Lee, Magnolia Muk Lan
AU - Wong, Wing Yan
AU - Chan, Brandon Dow
AU - Yang, Qianqian
AU - Wong, Wing Tak
AU - Tai, Chi Shing
AU - Lee, Chi Sing
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85044596119&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-03546-9
DO - 10.1038/s41467-018-03546-9
M3 - Journal article
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1283
ER -