Vitamin D5

Last updated
Vitamin D5
Vitamin D5 structure.svg
Names
IUPAC name
(1S,3Z)-3-[(2E)-2-[(1R,3aS,7aR)-1-[(1R,4S)-4-ethyl-1,5-dimethylhexyl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylene-1-cyclohexanol
Other names
Sitocalciferol
(5Z,7E)-(3S)-9,10-secoporiferasta-5,7,10(19)-trien-3-ol
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
PubChem CID
UNII
  • InChI=1S/C29H48O/c1-7-23(20(2)3)12-10-22(5)27-16-17-28-24(9-8-18-29(27,28)6)13-14-25-19-26(30)15-11-21(25)4/h13-14,20,22-23,26-28,30H,4,7-12,15-19H2,1-3,5-6H3/b24-13+,25-14-/t22-,23+,26+,27-,28+,29-/m1/s1 Yes check.svgY
    Key: RMDJVOZETBHEAR-GHTRHTQZSA-N Yes check.svgY
  • InChI=1/C29H48O/c1-7-23(20(2)3)12-10-22(5)27-16-17-28-24(9-8-18-29(27,28)6)13-14-25-19-26(30)15-11-21(25)4/h13-14,20,22-23,26-28,30H,4,7-12,15-19H2,1-3,5-6H3/b24-13+,25-14-/t22-,23+,26+,27-,28+,29-/m1/s1
    Key: RMDJVOZETBHEAR-GHTRHTQZBN
  • O[C@@H]1CC(\C(=C)CC1)=C\C=C2/CCC[C@]3([C@H]2CC[C@@H]3[C@H](C)CC[C@H](CC)C(C)C)C
Properties
C29H48O
Molar mass 412.702 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Vitamin D5 (sitocalciferol) is a form of vitamin D.

Contents

Research

Analogs of calcitriol, a form of vitamin D3, have been proposed for use as antitumor agents. [1] [2] [3] Studies on vitamin D3 have shown inhibition of cell proliferation in prostate cancer, but high doses of vitamin D3 result in hypercalcemia. The effects of vitamin D5 on prostate cancer have also been studied, and unlike vitamin D3, vitamin D5 does not cause hypercalcemia while inhibiting tumor cell proliferation. [4] The most researched analogue of vitamin D5 as an antitumor agent is 1α-hydroxyvitamin D5.

1α-Hydroxyvitamin D5

1α-Hydroxyvitamin D5 is a chemical derivative of vitamin D5. The motive to study 1α-hydroxyvitamin D5 as a potential pharmaceutical drug stemmed from the tendency of calcitriol, a natural metabolite produced in the kidney, to cause toxic hypercalcemia in patients when dosed at concentrations needed to interrupt prostate cancer cells' cycle and stimulate apoptosis. [5] [6] And while supplementation with dexamethasone decreases hypercalcemia, [7] bypassing it with an equally effective tumor suppressant would reduce patient cost and stress. Thus, the therapeutic effects of 1α-Hydroxyvitamin D5 as a potential antitumor agent without the side effects of calcitriol became a topic of study.

1α-Hydroxyvitamin D5 was first synthesized in 1997 by researchers in the Department of Chemistry at the University of Chicago, under Robert M. Moriarty and Dragos Albinescu. By 2005, the group had revised its synthesis method for a more streamlined, higher yield-producing route. It involved the photochemical conversion of precursor 7-dehydrositosteryl acetate to contain a conjugated triene system, a hallmark of this analog, followed by hydroxylation, photoisomerization, and deprotection steps. Their overall yield was 48%. [8]

See also

Related Research Articles

<span class="mw-page-title-main">Calcium metabolism</span> Movement and regulation of calcium ions in and out of the body

Calcium metabolism is the movement and regulation of calcium ions (Ca2+) in (via the gut) and out (via the gut and kidneys) of the body, and between body compartments: the blood plasma, the extracellular and intracellular fluids, and bone. Bone acts as a calcium storage center for deposits and withdrawals as needed by the blood via continual bone remodeling.

<span class="mw-page-title-main">Cholecalciferol</span> Vitamin D3, a chemical compound

Cholecalciferol, also known as vitamin D3 and colecalciferol, is a type of vitamin D that is made by the skin when exposed to sunlight; it is found in some foods and can be taken as a dietary supplement.

<span class="mw-page-title-main">Calcitriol</span> Active form of vitamin D

Calcitriol is the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It is a hormone which binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the expression of many genes. Calcitriol increases blood calcium (Ca2+) mainly by increasing the uptake of calcium from the intestines.

<span class="mw-page-title-main">Androgen receptor</span> Mammalian protein found in humans

The androgen receptor (AR), also known as NR3C4, is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.

<span class="mw-page-title-main">Calcipotriol</span> Chemical compound

Calcipotriol, also known as calcipotriene, is a synthetic derivative of calcitriol, a form of vitamin D. It is used in the treatment of psoriasis. It is safe for long-term application in psoriatic skin conditions.

<span class="mw-page-title-main">Vitamin D toxicity</span> Human disease

Vitamin D toxicity, or hypervitaminosis D is the toxic state of an excess of vitamin D. The normal range for blood concentration in adults is 20 to 50 nanograms per milliliter (ng/mL).

<span class="mw-page-title-main">Vitamin D receptor</span> Transcription factor activated by vitamin D

The vitamin D receptor (VDR also known as the calcitriol receptor) is a member of the nuclear receptor family of transcription factors. Calcitriol (the active form of vitamin D, 1,25-(OH)2vitamin D3) binds to VDR, which then forms a heterodimer with the retinoid-X receptor. The VDR heterodimer then enters the nucleus and binds to Vitamin D responsive elements (VDRE) in genomic DNA. VDR binding results in expression or transrepression of many specific gene products. VDR is also involved in microRNA-directed post transcriptional mechanisms. In humans, the vitamin D receptor is encoded by the VDR gene located on chromosome 12q13.11.

<span class="mw-page-title-main">RANKL</span> Mammalian protein found in Homo sapiens

Receptor activator of nuclear factor kappa-Β ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiation factor (ODF), is a protein that in humans is encoded by the TNFSF11 gene.

<span class="mw-page-title-main">Calcifediol</span> Chemical compound

Calcifediol, also known as calcidiol, 25-hydroxycholecalciferol, or 25-hydroxyvitamin D3 (abbreviated 25(OH)D3), is a form of vitamin D produced in the liver by hydroxylation of vitamin D3 (cholecalciferol) by the enzyme vitamin D 25-hydroxylase. Calcifediol can be further hydroxylated by the enzyme 25(OH)D-1α-hydroxylase, primarily in the kidney, to form calcitriol (1,25-(OH)2D3), which is the active hormonal form of vitamin D.

25-Hydroxyvitamin D 1-alpha-hydroxylase Mammalian protein found in Homo sapiens

25-Hydroxyvitamin D 1-alpha-hydroxylase also known as calcidiol 1-monooxygenase or cytochrome p450 27B1 (CYP27B1) or simply 1-alpha-hydroxylase is a cytochrome P450 enzyme that in humans is encoded by the CYP27B1 gene.

<span class="mw-page-title-main">Calcitroic acid</span> Chemical compound

Calcitroic acid (1α-hydroxy-23-carboxy-24,25,26,27-tetranorvitamin D3) is a major metabolite of 1α,25-dihydroxyvitamin D3 (calcitriol). Around 1980, scientists first reported the isolation of calcitroic acid from the aqueous extract of radioactively treated animals' livers and intestines. Subsequent researches confirmed calcitroic acid to be a part of enterohepatic circulation. Often synthesized in the liver and kidneys, calcitroic acid is generated in the body after vitamin D is first converted into calcitriol, an intermediate in the fortification of bone through the formation and regulation of calcium in the body. These pathways managed by calcitriol are thought to be inactivated through its hydroxylation by the enzyme CYP24A1, also called calcitriol 24-hydroxylase. Specifically, It is thought to be the major route to inactivate vitamin D metabolites. The hydroxylation and oxidation reactions will yield either calcitroic acid via the C24 oxidation pathway or 1,25(OH2)D3-26,23-lactone via the C23 lactone pathway.

<span class="mw-page-title-main">Nuclear receptor coactivator 2</span> Protein-coding gene in the species Homo sapiens

The nuclear receptor coactivator 2 also known as NCoA-2 is a protein that in humans is encoded by the NCOA2 gene. NCoA-2 is also frequently called glucocorticoid receptor-interacting protein 1 (GRIP1), steroid receptor coactivator-2 (SRC-2), or transcriptional mediators/intermediary factor 2 (TIF2).

<span class="mw-page-title-main">CYP24A1</span>

Cytochrome P450 family 24 subfamily A member 1 (abbreviated CYP24A1) is a member of the cytochrome P450 superfamily of enzymes encoded by the CYP24A1 gene. It is a mitochondrial monooxygenase which catalyzes reactions including 24-hydroxylation of calcitriol (1,25-dihydroxyvitamin D3). It has also been identified as vitamin D3 24-hydroxylase.(EC 1.14.15.16)

<span class="mw-page-title-main">24,25-Dihydroxycholecalciferol</span> Chemical compound

24,25-Dihydroxycholecalciferol, also known as 24,25-dihydroxyvitamin D3 and (24R)-hydroxycalcidiol (abbreviated as 24(R),25-(OH)2D3), is a compound which is closely related to 1,25-dihydroxyvitamin D3, the active form of vitamin D3. Like vitamin D3 itself and calcifediol (25-hydroxyvitamin D3), it is inactive as a hormone both in vitro and in vivo. It was first identified in 1972 in the laboratory of Hector DeLuca and Michael F. Holick.

<span class="mw-page-title-main">Vitamin D</span> Group of fat-soluble secosteroids

Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and for many other biological effects. In humans, the most important compounds in this group are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol).

<span class="mw-page-title-main">Michael F. Holick</span> American physician–scientist

Michael F. Holick is an American adult endocrinologist, specializing in vitamin D, such as the identification of both calcidiol, the major circulating form of vitamin D, and calcitriol, the active form of vitamin D. His work has been the basis for diagnostic tests and therapies for vitamin D-related diseases. He is a professor of medicine at the Boston University Medical Center and editor-in-chief of the journal Clinical Laboratory.

<span class="mw-page-title-main">Galeterone</span> Chemical compound

Galeterone is a steroidal antiandrogen which was under development by Tokai Pharmaceuticals for the treatment of prostate cancer. It possesses a unique triple mechanism of action, acting as an androgen receptor antagonist, androgen receptor down regulator, and CYP17A1 inhibitor, the latter of which prevents the biosynthesis of androgens. As a CYP17A1 inhibitor, galeterone shows selectivity for 17,20-lyase over 17α-hydroxylase.

<span class="mw-page-title-main">Eldecalcitol</span> Chemical compound

Eldecalcitol is an analog of calcitriol, the active form of vitamin D.

Vitamin D3 24-hydroxylase (EC 1.14.15.16, CYP24A1) is an enzyme with systematic name calcitriol,NADPH:oxygen oxidoreductase (24-hydroxylating). This enzyme catalyses the following chemical reaction

A hormone-sensitive cancer, or hormone-dependent cancer, is a type of cancer that is dependent on a hormone for growth and/or survival. Examples include breast cancer, which is dependent on estrogens like estradiol, and prostate cancer, which is dependent on androgens like testosterone.

References

  1. ↑ Mehta RG, Moriarty RM, Mehta RR, Penmasta R, Lazzaro G, Constantinou A, Guo L (February 1997). "Prevention of preneoplastic mammary lesion development by a novel vitamin D analogue, 1alpha-hydroxyvitamin D5". Journal of the National Cancer Institute. 89 (3): 212–8. doi: 10.1093/jnci/89.3.212 . PMID   9017001.
  2. ↑ Murillo G, Mehta RG (October 2005). "Chemoprevention of chemically-induced mammary and colon carcinogenesis by 1alpha-hydroxyvitamin D5". The Journal of Steroid Biochemistry and Molecular Biology. 97 (1–2): 129–36. doi:10.1016/j.jsbmb.2005.06.008. PMID   16051482. S2CID   24400116.
  3. ↑ Mehta RG (October 2004). "Stage-specific inhibition of mammary carcinogenesis by 1alpha-hydroxyvitamin D5". European Journal of Cancer. 40 (15): 2331–7. doi:10.1016/j.ejca.2004.05.025. PMID   15454260.
  4. ↑ Mooso B, Madhav A, Johnson S, Roy M, Moore ME, Moy C, Loredo GA, Mehta RG, Vaughan AT, Ghosh PM (November 2010). "Androgen Receptor regulation of Vitamin D receptor in response of castration-resistant prostate cancer cells to 1α-Hydroxyvitamin D5 - a calcitriol analog". Genes & Cancer. 1 (9): 927–940. doi:10.1177/1947601910385450. PMC   3089062 . PMID   21552398.
  5. ↑ Beer, Tomasz M.; Myrthue, Anne (March 2004). "Calcitriol in cancer treatment: from the lab to the clinic". Molecular Cancer Therapeutics. 3 (3): 373–381. doi: 10.1158/1535-7163.373.3.3 . ISSN   1535-7163. PMID   15026558. S2CID   7540584.
  6. ↑ Mooso, Benjamin; Madhav, Anisha; Johnson, Sherra; Roy, Mohana; Moore, Mary E.; Moy, Christabel; Loredo, Grace A.; Mehta, Rajendra G.; Vaughan, Andrew T.M.; Ghosh, Paramita M. (September 2010). "Androgen Receptor Regulation of Vitamin D Receptor in Response of Castration-Resistant Prostate Cancer Cells to 1α-Hydroxyvitamin D5". Genes & Cancer. 1 (9): 927–940. doi:10.1177/1947601910385450. ISSN   1947-6019. PMC   3089062 . PMID   21552398.
  7. ↑ Johnson, Candace S.; Muindi, Josephia R.; Hershberger, Pamela A.; Trump, Donald L. (July 2006). "The antitumor efficacy of calcitriol: preclinical studies". Anticancer Research. 26 (4A): 2543–2549. ISSN   0250-7005. PMID   16886662.
  8. ↑ Moriarty, Robert M.; Albinescu, Dragos (September 2005). "Synthesis of 1α-Hydroxyvitamin D5Using a Modified Two Wavelength Photolysis for Vitamin D Formation". The Journal of Organic Chemistry. 70 (19): 7624–7628. doi:10.1021/jo050853f. ISSN   0022-3263. PMID   16149791.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.