Design,synthesis,and biological evaluation of novel chrysin derivatives as poly(ADP-ribose)polymerase 1(PARP1)inhibitors for the treatment of breast cancer  

作　　者：YANG Yao TONG Jing XIE Xianshun CAO Hong FU Yong LUO Yong LIU Shan CHEN Wen YANG Ning 

机构地区：[1]Hengyang Medical School,University of South China,Hengyang 421200,China [2]Emergency Department,Hengyang Medical School,The Second Affiliated Hospital,University of South China,Hengyang 421200,China [3]Hengyang Medical School,The Second Affiliated Hospital,University of South China,Hengyang 421200,China [4]Hemato-oncology Department,Hengyang Medical School,The Second Affiliated Hospital,University of South China,Hengyang 421200,China [5]Department of Breast and Thyroid Surgery,Hengyang Medical School,The Second Affiliated Hospital,University of South China,Hengyang 421200,China

出　　处：《Chinese Journal of Natural Medicines》2024年第5期455-465,共11页中国天然药物（英文版）

基　　金：This work was supported by the Clinical Research Center for Breast&Thyroid Disease Prevention in Hunan Province(No.2018SK4001);the Scientific Research Project of Hunan Provincial Health Commission(No.20201969)。

摘　　要：In this study,we reported the discovery and structure-activity relationship analysis of chrysin derivatives as a new class of inhibitors targeting poly(ADP-ribose)polymerase 1(PARP1).Among these derivatives,compound 5d emerged as the most effective chrysin-based inhibitor of PARP1,with an IC50 value of 108 nmol·L^(-1).This compound significantly inhibited the proliferation and migration of breast cancer cell lines HCC-1937 and MDA-MB-436 by inducing DNA damage.Furthermore,5d induced apoptosis and caused an extended G1/S-phase in these cell lines.Molecular docking studies revealed that 5d possesses a strong binding affinity toward PARP1.In vivo,in a xenograft model,5d effectively reduced tumor growth by downregulating PARP1 expression.Overall,compound 5d shows promise as a potential therapeutic agent for the treatment of BRCA wild-type breast cancer.

关 键 词：Chrysin derivatives PARP1 Antitumor DNA damage Small molecules 

分 类 号：R914[医药卫生—药物化学]