Vitamin D
5 (sitocalciferol) is a form of
vitamin D
Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
.
Research
Analogs of
calcitriol
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 ...
, a form of vitamin D
3, have been proposed for use as antitumor agents.
Studies on vitamin D
3 have shown inhibition of cell proliferation in
prostate cancer, but high doses of vitamin D
3 result in
hypercalcemia. The effects of vitamin D
5 on prostate cancer have also been studied, and unlike vitamin D
3, vitamin D
5 does not cause
hypercalcemia while inhibiting tumor cell proliferation. The most researched analogue of vitamin D
5 as an antitumor agent is 1α-hydroxyvitamin D
5.
1α-Hydroxyvitamin D5
1α-Hydroxyvitamin D
5 is a chemical derivative of vitamin D
5. The motive to study 1α-hydroxyvitamin D
5 as a potential pharmaceutical drug stemmed from the tendency of calcitriol, a natural metabolite produced in the
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
, to cause toxic hypercalcemia in patients when dosed at concentrations needed to interrupt
prostate cancer cells' cycle and stimulate
apoptosis. And while supplementation with
dexamethasone
Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena ...
decreases hypercalcemia, bypassing it with an equally effective tumor suppressant would reduce patient cost and stress. Thus, the therapeutic effects of 1α-Hydroxyvitamin D
5 as a potential antitumor agent without the side effects of calcitriol became a topic of study.
1α-Hydroxyvitamin D
5 was first synthesized in 1997 by researchers in the Department of Chemistry at the
University of Chicago
The University of Chicago (UChicago, Chicago, U of C, or UChi) is a private university, private research university in Chicago, Illinois. Its main campus is located in Chicago's Hyde Park, Chicago, Hyde Park neighborhood. The University of Chic ...
, 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
In chemistry, photoisomerization is a form of isomerization induced by photoexcitation. Both reversible and irreversible photoisomerizations are known for photoswitchable compounds. The term "photoisomerization" usually, however, refers to a re ...
, and
deprotection
A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis.
In man ...
steps. Their overall yield was 48%.
See also
*
7-Dehydrositosterol
*
Calcipotriene
References
{{Vitamin
Vitamin D