Design, Synthesis, and Structure-Activity relationships of Evodiamine-Based topoisomerase (Top)/Histone deacetylase (HDAC) dual inhibitors

Autor:	Fugui Zhu, Xiangguo Meng, Huixin Liang, Chunquan Sheng, Guoqiang Dong, Dan Liu, Shanchao Wu
Rok vydání:	2021
Předmět:	Organic Chemistry Antineoplastic Agents Biochemistry Histone Deacetylases Histone Deacetylase Inhibitors Structure-Activity Relationship Cell Line Tumor Drug Design Drug Discovery Quinazolines Humans Drug Screening Assays Antitumor Molecular Biology Cell Proliferation
Zdroj:	Bioorganic chemistry. 122
ISSN:	1090-2120
Popis:	On the basis of synergistic effect between topoisomerase (Top) and histone deacetylase (HDAC) inhibitors, a series of novel evodiamine-based Top/HDAC dual inhibitors were designed and synthesized. Systematic structure-activity relationship (SAR) studies led to the discovery of compounds 29b and 45b, which simultaneously inhibited Top and HDAC and exhibited potent antitumor activities against the HCT116 cell line. Compounds 29b and 45b efficiently induced apoptosis with G2 cell cycle arrest and significantly inhibited cellular HDACs in HCT116 cells with good in vitro metabolic stabilities. Collectively, this work provides valuable SAR information and lead compounds for evodiamine-based Top/HDAC dual inhibitors.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::755b10843ab5d10dcf12d582775332ea https://pubmed.ncbi.nlm.nih.gov/35286923 Zobrazit plný text záznamu Full Text from ScienceDirect