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Publication Abstract from PubMed

1alpha,25-Dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3), 1] is an active form of vitamin D(3) and regulates various biological phenomena, including calcium and phosphate homeostasis, bone metabolism, and immune response via binding to and activation of vitamin D receptor (VDR). Lithocholic acid (LCA, 2) was identified as a second endogenous agonist of VDR, though its potency is very low. However, the lithocholic acid derivative 3 (Dcha-20) is a more potent agonist than 1alpha,25(OH)(2)D(3), (1), and its carboxyl group has similar interactions to the 1,3-dihydroxyl groups of 1 with amino acid residues in the VDR ligand-binding pocket. Here, we designed and synthesized amide derivatives of 3 in order to clarify the role of the carboxyl group. The synthesized amide derivatives showed HL-60 cell differentiation-inducing activity with potency that depended upon the substituent on the amide nitrogen atom. Among them, the N-cyanoamide 6 is more active than either 1 or 3.

Lithocholic Acid Amides as Potent Vitamin D Receptor Agonists.,Yoshihara A, Kawasaki H, Masuno H, Takada K, Numoto N, Ito N, Hirata N, Kanda Y, Ishizawa M, Makishima M, Kagechika H, Tanatani A Biomolecules. 2022 Jan 14;12(1):130. doi: 10.3390/biom12010130. PMID:35053278^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.