| Abstract | Four analogues of vitamin D3 with an oxygen atom in the side chain skeleton were synthesized to determine whether their differentiation-inducing activity could be separated structurally from their activity to induce hypercalcemia. The order of the in vitro potency to reduce nitroblue tetrazolium in human myeloid leukemia cells (HL-60) was 22-oxa-1 alpha, 25-(OH)2D3 greater than 1 alpha, 25-(OH)2D3 greater than 20-oxa-1 alpha, 25-(OH)2D3 not equal to 22-oxa-1 alpha-(OH)D3 greater than 1 alpha-(OH)D3 greater than 20-oxa-1 alpha-(OH)D3. 22-Oxa-1 alpha, 25-(OH)2D3 was also about 10-times more potent than 1 alpha, 25-(OH)2D3 in suppressing proliferation and inducing differentiation of mouse myelomonocytic leukemia cells (WEHI-3), but the former was much weaker than the latter in inducing the release of 45Ca from prelabeled fetal mouse calvaria. These results suggest that the differentiation-inducing activity of vitamin D compounds can be separated structurally from their activity to induce hypercalcemia. |
| Authors | J Abe, M Morikawa, K Miyamoto, S Kaiho, M Fukushima, C Miyaura, E Abe, T Suda, Y Nishii
(Affiliation: Research Laboratories, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.)
|
| Journal | FEBS letters
(FEBS Lett)
Vol. 226
Issue 1
Pg. 58-62
(Dec 21 1987)
ISSN: 0014-5793 NETHERLANDS |
| PMID | 2826255
(Publication Type: Comparative Study, Journal Article)
|
| Chemical References |
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| Topics |
- Animals
- Bone Resorption
(drug effects)
- Bone and Bones
(metabolism)
- Calcium
(metabolism)
- Cell Differentiation
(drug effects)
- Cell Division
(drug effects)
- Cell Line
- Cholecalciferol
(pharmacology)
- Humans
- Mice
- Mice, Inbred Strains
- Structure-Activity Relationship
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