Exploring Marine-Derived Ascochlorins as Novel Human Dihydroorotate Dehydrogenase Inhibitors for Treatment of Triple-Negative Breast Cancer

Human dihydroorotate dehydrogenase (hDHODH) is an attractive tumor target essential to de novo pyrimidine biosynthesis. Novel potent hDHODH inhibitors with low toxicity are urgently needed. Herein, we demonstrate the isolation of 25 ascochlorin (ASC) derivatives, including 13 new ones, from the cora...

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Veröffentlicht in:	Journal of medicinal chemistry 2021-09, Vol.64 (18), p.13918-13932
Hauptverfasser:	Luo, Xiaowei, Cai, Guodi, Guo, Yinfeng, Gao, Chenghai, Huang, Weifeng, Zhang, Zhenhua, Lu, Humu, Liu, Kai, Chen, Jianghe, Xiong, Xiaofeng, Lei, Jinping, Zhou, Xuefeng, Wang, Junjian, Liu, Yonghong
Format:	Artikel
Sprache:	eng
Schlagworte:	Acremonium - chemistry Alkenes - chemistry Alkenes - isolation & purification Alkenes - metabolism Alkenes - therapeutic use Animals Antineoplastic Agents - chemistry Antineoplastic Agents - isolation & purification Antineoplastic Agents - metabolism Antineoplastic Agents - therapeutic use Apoptosis - drug effects Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Chemistry, Medicinal Dihydroorotate Dehydrogenase - antagonists & inhibitors Dihydroorotate Dehydrogenase - metabolism Enzyme Inhibitors - chemistry Enzyme Inhibitors - isolation & purification Enzyme Inhibitors - metabolism Enzyme Inhibitors - therapeutic use Humans Life Sciences & Biomedicine Mice Mice, Inbred NOD Mice, SCID Molecular Structure Pharmacology & Pharmacy Phenols - chemistry Phenols - isolation & purification Phenols - metabolism Phenols - therapeutic use Science & Technology Structure-Activity Relationship Triple Negative Breast Neoplasms - drug therapy Triple Negative Breast Neoplasms - pathology Xenograft Model Antitumor Assays
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