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, William C S
AU - Lee, Chi Sing
N1 - Funding Information:
This paper is dedicated to Professor Craig J. Forsyth on the occasion of his 60th birthday. This work is financially supported by the National Natural Science Foundation of China (21272012, 21502002 and 21572006), Natural Science Foundation of Guangdong Province, China (2017A030313042), Shenzhen Science, Technology and Innovation Committee (JCYJ20150626111042525, JCYJ20160330095659560 and JCYJ20160428153421635), Chinese Postdoctoral Science Foundation (2015M580910), Hong Kong Research Grants Council (Collaborative Research Grants, CRF PolyU11/ CRF/13E; General Research Fund, GRF PolyU 12103515), Hong Kong Polytechnic University [University Research Facility for Chemical and Environmental Analysis (UCEA), Area of Excellence Grants (1-ZVGG)] and Peking University Shenzhen Graduate School. A special acknowledgement is made to Dr. Wesley Ting-kwok Chan (Hong Kong Polytechnic University) for the X-ray crystallography of compounds (±)−2, (±)−12 and (±)−16–17.
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
C2 - 29599469
AN - SCOPUS:85044596119
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1283
ER -
