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Synthesis, Molecular Docking and Biological Evaluation of A-Ring-Carborane-Vitamin D Analogues
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Synthesis, Molecular Docking and Biological Evaluation of A-Ring-Carborane-Vitamin D Analogues
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Journal Article
Synthesis, Molecular Docking and Biological Evaluation of A-Ring-Carborane-Vitamin D Analogues
2025
Overview
The active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25D3), regulates a number of physiological and pathological processes, including cell proliferation and differentiation. Thousands of analogues of 1,25D3 have been developed with the aim of selective effects for medical use. Here we describe the synthesis of two new unconventional vitamin D analogues bearing A-ring modifications with ortho-carborane (dicarba-o-closo-1,2-dodecaborane) units. The ligands function as agonists for VDR with similar antiproliferative activities as 1,25D3. Whereas mice treated with the analogues 4 and 5 exhibited similar hypercalcemic activities as 1,25D3, only compound 4 and 1,25D3 induced the strong activation of CYP24A1 mRNA expression but not compound 5.
Publisher
MDPI AG,MDPI
Subject
/ Animals
/ Calcitriol - analogs & derivatives
/ Calcitriol - chemical synthesis
/ Cell Proliferation - drug effects
/ Chloride
/ docking
/ Humans
/ Ligands
/ Mice
/ Molecular Docking Simulation
/ Receptors, Calcitriol - agonists
/ Receptors, Calcitriol - chemistry
/ Receptors, Calcitriol - metabolism
/ RNA
/ Structure-Activity Relationship
/ Vitamin D - analogs & derivatives
/ Vitamin D - chemical synthesis
/ Vitamin D3 24-Hydroxylase - genetics
