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N Kubodera

Publications and source records attributed to N Kubodera.

43 records · Page 3Linked to original sources
PubMed1992

Synthetic studies of vitamin D analogues. X. Synthesis and biological activities of 1 alpha,25-dihydroxy-21-norvitamin D3.

1 alpha,25-Dihydroxy-21-norvitamin D3 (3) was synthesized from 1 alpha-hydroxydehydroepiandrosterone (4). Certain biological properties of 3 were examined in comparison with those of 1 alpha,25-dihydroxyvitamin D3 (1) and 1 alpha,25-dihydroxy-21-nor-20-oxavitamin D3 (2) to evaluate the effect of the 21-methyl substituent on biological activities. The differentiation-inducing activity of 3 towards human myeloid leukemia cells was approximately one-fifth of that of 1, while in the binding affinity with chick intestinal cytosolic receptor, 3 was about one-tenth of that of 1. The rather weak effect of 3 on serum calcium levels in normal mice at a dosage of 500 micrograms/kg (intravenous administration) indicates that the essential importance of the 21-methyl moiety may lie in its effect on the regulation of calcium metabolism.

Animals↗
PubMed1991

Synthetic studies of vitamin D analogues. IX. Synthesis and differentiation-inducing activity of 1 alpha,25-dihydroxy-23-oxa-, thia-, and azavitamin D3.

Three vitamin D3 analogues, 1 alpha,25-dihydroxy-23-oxavitamin D3 (3), 1 alpha,25-dihydroxy-23-thiavitamin D3 (4) and 1 alpha,25-dihydroxy-23-azavitamin D3 (5) were synthesized. In the differentiation-inducing activity of human myeloid leukemia cells into macrophages in vitro, the 23-aza analogue (5) showed the least activity, while no remarkable differences were observed between the 23-oxa analogue (3) and the 23-thia analogue (4), which were less active than 1 alpha,25-dihydroxyvitamin D3 (1).

Calcitriol↗
PubMed1980

Enhancement of PGI2 formation by a new vasodilator, 2-nicotinamidoethyl nitrate in the coupled system of platelets and aortic microsomes.

Exogenous arachidonate addition to the coupled system of platelets and aortic microsomes resulted in production of TXA2 and PGI2 (detected as the stable degradation products, TXB2 and 6-keto PGF1 alpha, respectively). Imidazole, papaverine and dipyridamole increased PGI2 and decreased TXA2 in the coupled system. All of these agents inhibited TXA2 formation by platelets from arachidonate. Nitroglycerin did not show any effect on PGI2 and TXA2 formation in the coupled system and on TXA2 formation by platelets. In contrast with these compounds, in spite of showing no inhibitory effect on TXA2 formation by platelets alone, 2-nicotinamidoethyl nitrate (SG-75) increased PGI2 and decreased TXA2 in the coupled system. It is suggested that SG-75 accelerated the conversion of PGH2 to PGI2 so that smaller amounts of TXA2 was produced in the coupled system.

Animals↗
PubMedDate not supplied

Synthesis and biological characterization of 1alpha,24,25-trihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) (24-hydroxylated ED-71).

24-Hydroxylated derivatives were synthesized in 24(R) and 24(S) forms by the convergent method as analogs related to 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3). In the convergent synthesis, the A-ring fragment, synthesized from diethyl D-tartarate, and the C/D-ring fragments in 24(R) and 24(S) forms (vitamin D numbering), obtained from vitamin D(2) via the Inhoffen-Lythgoe diol, were coupled in moderate yields to give 1alpha,24(R),25-trihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) and 1alpha,24(S),25-trihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3). In preliminary biological evaluations, 24-hydroxylation of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) caused weakened affinity to vitamin D binding protein in vitro and less calcemic activity in vivo compared to the parent compound. While the affinity to vitamin D receptor in 24(R) epimer was sustained, the affinity in 24(S) epimer was less than that of the parent compound.

Animals↗
PubMedDate not supplied

In vivo nuclear uptake of a vitamin D analog (OCT) in different tumor cell populations of FA-6 cancer xenograft in nude mice by receptor autoradiography.

1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25(OH)2D3] and its analogs have been shown to repress the production of parathyroid hormone-related peptide (PTHrP) in tumors, which is a major factor causing humoral hypercalcemia associated with various cancers. Since vitamin D analogs may be applicable to the treatment of cancer patients, the present study was undertaken to examine whether OCT, an analog with little calcemic activity, is incorporated into tumor tissues, and to identify cellular and subcellular sites of its specific uptake and retention. [26-3H]OCT was injected i.v. into nude mice inoculated with a human pancreatic carcinoma cell line (FA-6). At 1 hour after the injection, intracellular concentration of radioactivity was visualized by receptor (thaw-mount) autoradiography. The results indicate a heterogeneous distribution of radioactivity in nuclei of certain large cancer cells as well as in single or clustered small and elongated cells within the tumor, while connective tissue cells outside of the tumor remained free of nuclear labeling. The data suggest that OCT acts selectively at the genome of cancer cells during a certain maturational stage and also of a second population of small fibroblast-like cells that may have been transplanted with the tumor or are host-derived.

Animals↗