Design, synthesis and activity evaluation of Hedgehog inhibitor Itraconazole derivatives in A549 cells

被引：2

作者：

Cai, Jin ^{[1
]}

Chen, Xixi ^{[1
]}

You, Haoyuan ^{[1
]}

Li, Xiaojing ^{[1
]}

Ji, Min ^{[2
]}

机构：

[1] Southeast Univ, Sch Chem & Chem Engn, Nanjing 211189, Jiangsu, Peoples R China

[2] Southeast Univ, Sch Biol Sci & Med Engn, Nanjing 210096, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2022年 / 76卷

关键词：

Hedgehog signaling channel; Smoothened; Itraconazole derivatives; A549; SIGNALING PATHWAY; CANCER; TARGET;

D O I：

10.1016/j.bmcl.2022.129011

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Hedgehog signal channel, a channel that plays a role in the occurrence and development of a variety of cancers. We introduce the composition and mechanism of Hedgehog signal channel, and the anti-tumor mechanism. A series of derivatives were designed and synthesized with the Hedgehog signal channel inhibitor Itraconazole in clinical phase II as the precursor. Compared with the other inhibitors, Itraconazole has a weaker inhibitory effect on Hedgehog, and there are few studies on improving the anti proliferation ability of Itraconazole on cells. Therefore, using Itraconazole as the lead, we obtained a series of derivatives that can effectively inhibit Hedgehog channels. Compared with Itraconazole, compounds 12g and 12n had stronger inhibitory effects in A549 cells.

引用

页数：12

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