Add time:08/14/2019 Source:sciencedirect.com
Six A-ring analogs of 1α,25-dihydroxyvitamin D3 (1, 1α,25-(OH)2-D3) 3-deoxy-3-thia-1α,25-(OH)2-D3 (3), 3-deoxy-3-thia-1α,25-(OH)2-D3-3α-oxide (6), 3-deoxy-3-thia-1α,25-(OH)2-D3-3β-oxide (7) and the 5,6-trans counterparts 5, 8, and 9, respectively—were tested for their ability to inhibit 25-hydroxy-D3-1α-hydroxylase (1-OH-ase) in vitro in mitochondria isolated from kidneys of vitamin D deficient chicks. The six analogs were also evaluated in terms of their ability to bind to the chicken intestinal nuclear receptor (VDR) in comparison to the natural hormone 1α,25-(OH)2-D3. Analog 7 is not only the best inhibitor of the 1-OH-ase but it also binds effectively to the chick intestinal receptor. It is established that vitamin D analogs must have a 1α oxygen group for effective inhibition of the 1-OH-ase. This functional group is also needed for effective binding to the chick intestinal VDR.
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