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Synthetic analogues of vitamin D 3 with an oxygen atom in the side chain skeleton A trial of the development of vitamin D compounds which exhibit potent differentiation‐inducing activity without inducing hypercalcemia
Author(s) -
Abe Junko,
Morikawa Makiko,
Miyamoto Katsuhito,
Kaiho Shin-ichi,
Fukushima Masafumi,
Miyaura Chisato,
Abe Etsuko,
Suda Tatsuo,
Nishii Yasuho
Publication year - 1987
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(87)80550-1
Subject(s) - chemistry , vitamin d and neurology , side chain , vitamin , stereochemistry , potency , ascorbic acid , cellular differentiation , biological activity , in vitro , biochemistry , endocrinology , biology , organic chemistry , gene , polymer , food science
Four analogues of vitamin D 3 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‐1α25‐(OH) 2 D 3 > 1α,25‐(OH) 2 D 3 > 20‐oxa‐1α,25‐(OH) 2 D 3 ≒22‐oxa‐1α‐(OH) D 3 > 1α‐(OH)D 3 > 20‐oxa‐1α‐(OH)D 3 . 22‐Oxa‐1α,25‐(OH) 2 D 3 , was also about 10‐times more potent than 1α,25‐(OH) 2 D 3 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 45 Ca 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.