2. Academic Validation
  3. Design, synthesis and activity evaluation of Hedgehog inhibitor Itraconazole derivatives in A549 cells

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

  • Bioorg Med Chem Lett. 2022 Nov 15:76:129011. doi: 10.1016/j.bmcl.2022.129011.
Jin Cai 1,  Xixi Chen 2,  Haoyuan You 2,  Xiaojing Li 2,  Min Ji 3
Affiliations

Affiliations

  • 1 School of Chemistry and Chemical Engineering, Southeast University, Nanjing, Jiangsu 211189, PR China. Electronic address: caijin@seu.edu.cn.
  • 2 School of Chemistry and Chemical Engineering, Southeast University, Nanjing, Jiangsu 211189, PR China.
  • 3 School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, PR China.
PMID: 36184028 DOI: 10.1016/j.bmcl.2022.129011
Abstract

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.

Keywords

A549; Hedgehog signaling channel; Itraconazole derivatives; Smoothened.

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