TY - JOUR
T1 - Synthesis and Evaluation of Novel Anticancer Compounds Derived from the Natural Product Brevilin A
AU - Lee, Magnolia Muk Lan
AU - Chan, Brandon Dow
AU - Wong, Wing Yan
AU - Leung, Tsz Wing
AU - Qu, Zhao
AU - Huang, Junrong
AU - Zhu, Lizhi
AU - Lee, Chi Sing
AU - Chen, Sibao
AU - Tai, William C S
N1 - Funding Information:
This work was supported in part by the Hong Kong Research Grants Council General Research Fund (project no. 12103515) and the Health and Medical Research Fund, Food and Health Bureau, Hong Kong SAR (project no. 15161401), to W.C.-S.T.; and the Basic Research Foundation of the Shenzhen Science and Technology Innovation Committee (JCYJ20151030164022389 and JCYJ20160229173844278) and the National Natural Science Foundation of China (no. 81872769) to S.C. We would also like to thank Dr. Rachel Wai-Sum Li and the University Research Facility in Life Sciences (ULS) of the Hong Kong Polytechnic University for technical and equipment support.
PY - 2020/6/23
Y1 - 2020/6/23
N2 - Cancer is the second leading cause of death globally, responsible for an estimated 9.6 million deaths in 2018, and this burden continues to increase. Therefore, there is a clear and urgent need for novel drugs with increased efficacy for the treatment of different cancers. Previous research has demonstrated that brevilin A (BA) exerts anticancer activity in various cancers, including human multiple myeloma, breast cancer, lung cancer, and colon carcinoma, suggesting the anticancer potential present in the chemical scaffold of BA. Here, we designed and synthesized a small library of 12 novel BA derivatives and evaluated the biological anticancer effects of the compounds in various cancer cell lines. The results of this structure-activity relationship study demonstrated that BA derivatives BA-9 and BA-10 possessed significantly improved anticancer activity toward lung, colon, and breast cancer cell lines. BA-9 and BA-10 could more effectively reduce cancer cell viability and induce DNA damage, cell-cycle arrest, and apoptosis when compared with BA. Our findings represent a significant step forward in the development of novel anticancer entities.
AB - Cancer is the second leading cause of death globally, responsible for an estimated 9.6 million deaths in 2018, and this burden continues to increase. Therefore, there is a clear and urgent need for novel drugs with increased efficacy for the treatment of different cancers. Previous research has demonstrated that brevilin A (BA) exerts anticancer activity in various cancers, including human multiple myeloma, breast cancer, lung cancer, and colon carcinoma, suggesting the anticancer potential present in the chemical scaffold of BA. Here, we designed and synthesized a small library of 12 novel BA derivatives and evaluated the biological anticancer effects of the compounds in various cancer cell lines. The results of this structure-activity relationship study demonstrated that BA derivatives BA-9 and BA-10 possessed significantly improved anticancer activity toward lung, colon, and breast cancer cell lines. BA-9 and BA-10 could more effectively reduce cancer cell viability and induce DNA damage, cell-cycle arrest, and apoptosis when compared with BA. Our findings represent a significant step forward in the development of novel anticancer entities.
UR - http://www.scopus.com/inward/record.url?scp=85087403319&partnerID=8YFLogxK
U2 - 10.1021/acsomega.0c01276
DO - 10.1021/acsomega.0c01276
M3 - Journal article
AN - SCOPUS:85087403319
SN - 2470-1343
VL - 5
SP - 14586
EP - 14596
JO - ACS Omega
JF - ACS Omega
IS - 24
ER -
