Synthesis and Evaluation of Aromatic A-Ring 23-Oxavitamin D₃ Analogues as Hedgehog Pathway Inhibitors.

ABSTRACT: The Hedgehog (Hh) signaling pathway plays a crucial role in the initiation and progression of tumors, and Hh inhibitors have been used as potential chemotherapeutic agents for the treatment of basal cell carcinomas (BCCs). Vitamin D₃ (VD₃) and its derivatives have been identified as potent Hh inhibitors. However, the selectivity of VD₃ derivatives to vitamin D receptor (VDR) and the Hh signaling pathway still needs optimization. In this study, a series of aromatic A-ring mimics VD₃ analogues that contain a C-23 oxygen atom or incorporate C-25 hydroxyl on side chains were designed and synthesized. These compounds were tested in various cell lines for anti-Hh activity, with analogues 3j and 4i identified as potent inhibitors. Mechanis

SUBMITTER: Chen W 

PROVIDER: S-EPMC11855207 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature