Discovery of Novel N‑Heterocyclic-Fused Deoxypodophyllotoxin Analogues as Tubulin Polymerization Inhibitors Targeting the Colchicine-Binding Site for Cancer Treatment

• Published in: Journal of medicinal chemistry Vol. 65; no. 24; pp. 16774 - 16800
• Main Authors: Leng, Jiafu, Zhao, Yongjun, Sheng, Ping, Xia, Yuanzheng, Chen, Tingting, Zhao, Shifang, Xie, Shanshan, Yan, Xiangyu, Wang, Xiaobing, Yin, Yong, Kong, Lingyi
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 22.12.2022
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Binding Sites; Cell Line, Tumor; Cell Proliferation; Colchicine - metabolism; Drug Screening Assays, Antitumor; Endothelial Cells - metabolism; Humans; MCF-7 Cells; Neoplasms - drug therapy; Polymerization; Structure-Activity Relationship; Tubulin - metabolism; Tubulin Modulators - chemistry; Tubulin Modulators - pharmacology; Tubulin Modulators - therapeutic use

Natural products are a major source of anticancer agents and play critical roles in anticancer drug development. Inspired by the complexity-to-diversity strategy, novel deoxypodophyllotoxin (DPT) analogues were designed and synthesized. Among them, compound C3 exhibited the potent antiproliferative...