Biological activity of the C-1, C-3, C-25, β-D-glucopyranosides of 1,25-dihydroxyvitamin D3

J. M. Londowski, S. B. Kost, W. Meier, L. Labler, Rajiv Kumar

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Abstract

We have shown previously that the 3-β-D-glucopyranosides of vitamin D3, 1α-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 are biologically active in vivo. In order to determine whether the presence of the β-D-glucopyranoside moiety linked to either the C-3, the C-25 or the C-1 hydroxyl function of the molecule affected the biological activity of the conjugates 1, 2, or 3 derived from 1,25-dihydroxyvitamin D3, we administered increasing amounts of compounds to vitamin D-deficient rats maintained on a low calcium diet. The aglycone, 1,25-dihydroxvitamin D3 (4), also was administered to another group of such animals. When administered i.v., all three β-D-glucopyranosides increased intestinal calcium transport in doses as low as 50 pmol/rat. A dose of ~500 pmol/rat was required to increase bone calcium mobilization in these same animals. The three glucosides were found to be equally active in both biological responses. A dose of only 5 pmol of 1,25-dihydroxyvitamin D3 (4) increased both intestinal calcium transport and bone calcium mobilization. We also performed similar experiments after the p.o. administration of these compounds to vitamin D-deficient rats maintained on a low calcium diet. The glucopyranosides 1, 2 and 3 were able to increase calcium transport in the intestine, as well as mobilize bone calcium at doses of between 500 and 5000 pmol/rat. Once again, the compounds were equipotent, but were less active than 1,25-dihydroxyvitamin D3 (4). After the i.v. or p.o. doses of the glucosides, plasma concentrations of 1,25-dihydroxyvitamin D3 increased in a dose-dependent manner. We conclude that: 1) The C-3, C-25 and C-1 β-D-glucopyranosides of 1,25-dihydroxyvitamin D3 are biologically active and equipotent in vivo, most likely as a result of hydrolysis to the free aglycone and 2) they are less active than the aglycone in this respect.

Original languageEnglish (US)
Pages (from-to)837-840
Number of pages4
JournalJournal of Pharmacology and Experimental Therapeutics
Volume237
Issue number3
StatePublished - 1986

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Calcitriol
Calcium
Glucosides
Bone and Bones
Vitamin D
Diet
Calcifediol
Cholecalciferol
Hydroxyl Radical
Intestines
Hydrolysis

ASJC Scopus subject areas

  • Pharmacology

Cite this

Biological activity of the C-1, C-3, C-25, β-D-glucopyranosides of 1,25-dihydroxyvitamin D3 . / Londowski, J. M.; Kost, S. B.; Meier, W.; Labler, L.; Kumar, Rajiv.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 237, No. 3, 1986, p. 837-840.

Research output: Contribution to journalArticle

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abstract = "We have shown previously that the 3-β-D-glucopyranosides of vitamin D3, 1α-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 are biologically active in vivo. In order to determine whether the presence of the β-D-glucopyranoside moiety linked to either the C-3, the C-25 or the C-1 hydroxyl function of the molecule affected the biological activity of the conjugates 1, 2, or 3 derived from 1,25-dihydroxyvitamin D3, we administered increasing amounts of compounds to vitamin D-deficient rats maintained on a low calcium diet. The aglycone, 1,25-dihydroxvitamin D3 (4), also was administered to another group of such animals. When administered i.v., all three β-D-glucopyranosides increased intestinal calcium transport in doses as low as 50 pmol/rat. A dose of ~500 pmol/rat was required to increase bone calcium mobilization in these same animals. The three glucosides were found to be equally active in both biological responses. A dose of only 5 pmol of 1,25-dihydroxyvitamin D3 (4) increased both intestinal calcium transport and bone calcium mobilization. We also performed similar experiments after the p.o. administration of these compounds to vitamin D-deficient rats maintained on a low calcium diet. The glucopyranosides 1, 2 and 3 were able to increase calcium transport in the intestine, as well as mobilize bone calcium at doses of between 500 and 5000 pmol/rat. Once again, the compounds were equipotent, but were less active than 1,25-dihydroxyvitamin D3 (4). After the i.v. or p.o. doses of the glucosides, plasma concentrations of 1,25-dihydroxyvitamin D3 increased in a dose-dependent manner. We conclude that: 1) The C-3, C-25 and C-1 β-D-glucopyranosides of 1,25-dihydroxyvitamin D3 are biologically active and equipotent in vivo, most likely as a result of hydrolysis to the free aglycone and 2) they are less active than the aglycone in this respect.",
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N2 - We have shown previously that the 3-β-D-glucopyranosides of vitamin D3, 1α-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 are biologically active in vivo. In order to determine whether the presence of the β-D-glucopyranoside moiety linked to either the C-3, the C-25 or the C-1 hydroxyl function of the molecule affected the biological activity of the conjugates 1, 2, or 3 derived from 1,25-dihydroxyvitamin D3, we administered increasing amounts of compounds to vitamin D-deficient rats maintained on a low calcium diet. The aglycone, 1,25-dihydroxvitamin D3 (4), also was administered to another group of such animals. When administered i.v., all three β-D-glucopyranosides increased intestinal calcium transport in doses as low as 50 pmol/rat. A dose of ~500 pmol/rat was required to increase bone calcium mobilization in these same animals. The three glucosides were found to be equally active in both biological responses. A dose of only 5 pmol of 1,25-dihydroxyvitamin D3 (4) increased both intestinal calcium transport and bone calcium mobilization. We also performed similar experiments after the p.o. administration of these compounds to vitamin D-deficient rats maintained on a low calcium diet. The glucopyranosides 1, 2 and 3 were able to increase calcium transport in the intestine, as well as mobilize bone calcium at doses of between 500 and 5000 pmol/rat. Once again, the compounds were equipotent, but were less active than 1,25-dihydroxyvitamin D3 (4). After the i.v. or p.o. doses of the glucosides, plasma concentrations of 1,25-dihydroxyvitamin D3 increased in a dose-dependent manner. We conclude that: 1) The C-3, C-25 and C-1 β-D-glucopyranosides of 1,25-dihydroxyvitamin D3 are biologically active and equipotent in vivo, most likely as a result of hydrolysis to the free aglycone and 2) they are less active than the aglycone in this respect.

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