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BioAssay: AID 25549

Compound was tested for rate constant for the forward reaction of isomerization of previtamin D to vitamin D

The C-14 epimers of vitamin D, 14-epi-25-hydroxyvitamin D3 (4) and 14-epi-1 alpha, 25-dihydroxyvitamin D3 (5), were synthesized, and their isomerization via [1,7]-sigmatropic hydrogen shifts to the corresponding previtamin forms (4' and 5', respectively) was studied. The activation parameters of the [1,7]-sigmatropic hydrogen shifts were found to be similar to those of other vitamin D analogues, more ..
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 Tested Compounds
 Tested Compounds
All(3)
 
 
Unspecified(3)
 
 
 Tested Substances
 Tested Substances
All(3)
 
 
Unspecified(3)
 
 
 Related BioAssays
 Related BioAssays
AID: 25549
Data Source: ChEMBL (22670)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-21
Modify Date: 2014-05-19

Data Table ( Complete ):           All
Tested Compounds:
Description:
Title: 14-epi stereoisomers of 25-hydroxy- and 1 alpha,25-dihydroxyvitamin D3: synthesis, isomerization to previtamins, and biological studies.

Abstract: The C-14 epimers of vitamin D, 14-epi-25-hydroxyvitamin D3 (4) and 14-epi-1 alpha, 25-dihydroxyvitamin D3 (5), were synthesized, and their isomerization via [1,7]-sigmatropic hydrogen shifts to the corresponding previtamin forms (4' and 5', respectively) was studied. The activation parameters of the [1,7]-sigmatropic hydrogen shifts were found to be similar to those of other vitamin D analogues, although epimerization at C-14 shifts the equilibrium of the triene chromophore to the previtamin form. The in vivo biological activities of 4, 4', 5, and 5' in the chick in terms of their ability to elicit intestinal calcium absorption and bone calcium mobilization were determined. These vitamin D analogues, the first in the natural steroid series modified at the C-14 position, were essentially devoid of activity. The relative competitive indices (RCIs), derived in an in vitro assay reflecting the ability of these analogues to bind to the chick intestinal nuclear receptor, were determined. Analogues 4, 4', 5, and 5' had RCI values of 0.08, 0.01, 15, and 1.6, respectively, in comparison to the natural ligand, 1 alpha, 25-dihydroxyvitamin D3 (3), whose value is 100 by definition. Thus, the in vivo and in vitro data were somewhat at variance, particularly for 5, which bound significantly to the chick intestinal receptor. In vitro binding studies with the human serum vitamin D binding protein (DBP) were also conducted. The RCI values for human DBP reflects the ability of an analogue to bind to this protein in comparison to the hormone 3, whose value is 100. The measured RCI values for 4, 4', 5, and 5' were 3450, 90, 12, and 2.2, respectively. It is noteworthy that analogue 4 binds approximately 35 times more effectively than the parent hormone 3, but approximately 20 times less effectively than 25-hydroxyvitamin D3 (2).
(PMID: 8057286)
Comment
Putative Target:

ChEMBL Target ID: 22224
Target Type: ADMET
Pref Name: ADMET
Confidence: Default value - Target unknown or has yet to be assigned
Relationship Type: Default value - Target has yet to be curated
Categorized Comment
Assay Type: ADME

Assay Data Source: Scientific Literature

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1k1 activity commentk1 activity commentString
2k1 standard flagk1 standard flagInteger
3k1 qualifierk1 qualifierString
4k1 published valuek1 published valueFloats-1
5k1 standard valuek1 standard valueFloats-1

Data Table (Concise)
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