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

Bioorganic & Medicinal Chemistry Letters
2022.0

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.

Knowledge Graph

Similar Paper

Design, synthesis and activity evaluation of Hedgehog inhibitor Itraconazole derivatives in A549 cells
Bioorganic & Medicinal Chemistry Letters 2022.0
Structure–Activity Relationships for Itraconazole-Based Triazolone Analogues as Hedgehog Pathway Inhibitors
Journal of Medicinal Chemistry 2019.0
Inhibition of hedgehog signaling by stereochemically defined des-triazole itraconazole analogues
Bioorganic & Medicinal Chemistry Letters 2020.0
Truncated Itraconazole Analogues Exhibiting Potent Anti-Hedgehog Activity and Improved Drug-like Properties
ACS Medicinal Chemistry Letters 2019.0
Development of posaconazole-based analogues as hedgehog signaling pathway inhibitors
European Journal of Medicinal Chemistry 2019.0
Itraconazole Side Chain Analogues: Structure–Activity Relationship Studies for Inhibition of Endothelial Cell Proliferation, Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Glycosylation, and Hedgehog Signaling
Journal of Medicinal Chemistry 2011.0
Hedgehog pathway inhibitors of the acylthiourea and acylguanidine class show antitumor activity on colon cancer in vitro and in vivo
European Journal of Medicinal Chemistry 2018.0
Repurposing the Clinically Efficacious Antifungal Agent Itraconazole as an Anticancer Chemotherapeutic
Journal of Medicinal Chemistry 2016.0
Synthesis and biological evaluation of SANT-2 and analogues as inhibitors of the hedgehog signaling pathway
Bioorganic & Medicinal Chemistry 2009.0
New Pyrrole Derivatives with Potent Tubulin Polymerization Inhibiting Activity As Anticancer Agents Including Hedgehog-Dependent Cancer
Journal of Medicinal Chemistry 2014.0