Download 11. Hormones of the sexual glands

Lecture №11
Hormones of the sexual glands:
androgens and their semi-synthetic
derivatives, estrogens and their
synthetic analogues. Prostaglandins
as pharmaceuticals, their
properties, application.
ass. Medvid I.I.
Androgenic hormones
Male sex hormones called androgens (from the Greek word 'Andros'
- a man and "Genetic" - birth). Androgenic hormones are produced
by male gonads (testicular) during the puberty (sexual maturity
period).
Androgens are necessary for the formation of sexual sphere and
development of secondary sexual characteristics in men. They also
affect on various biochemical processes, not related to the
characteristics of sex - cause anabolic effects, affect on the
exchange of carbohydrates, lipids, cholesterol, electrolytes and other
staff.
Natural androgen is testosterone, which was at first dedicated in
1931 y. and synthesized in 1934 y.
Testosterone creates male and his lack in the old age in man
destroys the body, creating the conditions for heart attacks and
strokes.
Testosterone - unstable substance and is not used as a medicine. In
medicine, testosterone derivatives (esters) are used, which are
absorbed slowly and are more stanle; and also synthetic substitutes,
such as methyltestosterone. They all have medicinal properties of
the natural hormone.
Subsequent research established that the testosterone
effect is prolonged after the esterification by fatty acid.
Ester creates original depot at the injection site from
which they were gradually absorbed, while testosterone is
quickly removed from the body by the kidneys. One of the
most active and stable at the storage of testosterone esters
is testosterone propionate.
Methyltestosterone (17α-methyltestosterone), although by
the force of action is weaker then testosterone propionate,
but not destroyed by enzymes of the gastrointestinal tract
and remains activity at the oral admission.
Androgens are used for men with sexual
underdevelopment, functional disorders of sexual sphere
(eunuchoidism) and in old age with vascular and nerve
disorders.
Applied by older women (over 60) at the tumors of
reproductive organs, mammary glands of uterine bleeding,
as well as radiotherapy of ovarian cancer and breast
cancer.
Chemical signs of androgens
1.
2.
3.
4.
Derivatives of
androstane;
Availability of oxogroup(=О) in position
3;
In position 4 – double
bond;
Hydroxy-group (ОН) (can be
esterificated) in
position17.
1
19
CH3
18
CH3
12
17
11
13
16
9
2
8
10
3
15
7
5
4
14
6
Androstane
CH3
CH3
O
Testosterone
OH
General identification reactions on
androgenic hormones
On steroid system : Boscot’s reaction and reaction with
concentrated sulfate acid.
On keto-group in the position 3: reactions of the oximes,
hydrazones, isonicotinoyl hydrazones, phenyl hydrazones
formation.
Esters of androgenic hormones (testosterone propionate):
alkaline hydrolysis; hydroxamic reaction.
Alcoholic hydroxyl in 17β-position: formation of esters with
character melting temperature.
Testosterone propionate
(Testosteroni propionas) (SPhU 1.2)
CH3
OCOC2H5
CH3
3-Oxandrost-4-ene-17β-yl propanoate
or 17β-propioneoxyandrostene-4-one-3
Produce synthetically, based on cholesterol, which is produced with
the processing of lanolin and pork fat of animals.
Characters. White or almost white crystalline powder or colorless
crystals. Practically insoluble in water, freely soluble in alcohol and
acetone, soluble in fatty oils.
O
Identification of testosterone propionate
1.
2.
3.
4.
4.
5.
6.
Absorption spectrophotometry in IR-spectrum.
On steroid system – Boscot’s reaction. Intense
yellow fluorescence.
The drug is dissolved in СН3СООН conc., add by
drops bromine water - its bleaching occurs (reaction
on double bond).
Establish a melting point of testosterone derived as a
result of alkaline hydrolysis.
On ester group – hydroxamic reaction (red-brown
color).
On oxo-group in position 3 – oxime formation,
which can be identified by the temperature of
melting.
UV-spectrophotometry.
Assay of testosterone
UV-spectrophotometry (index method).
Photocolorimetry (based on the reaction between the drug with
isoniazid and establishment isonicotinoylhydrazone, colored in
yellow).
Storage and application
In tightly corked container, protected from moisture and light action.
Androgenic drug for the treatment of climacteric, vascular and
nerve disorders and cancers of breast and ovaries in women. Enter
by i/m way in oil solutions.
Issue – amp. 1,0 and 5,0 % solution in oil.
Omnadren – oil solution for injection amp. 1 ml №5 (contains a
mixture of testosterone esters: propionate, phenylpropionate,
capronate, isocapronate).
Andriol (testosterone undecanoate) – caps. 40 mg № 30;
Androgel (testosteron) – gel for the external usage 2,5 or 5 g №10.
Proviron (mesterolone, derivative of 5-androstanone (3)) – tabl. by
25 mg №20.
Testosterone enanthate (Testosteroni
enanthas)
CH3
OCO(CH2)5CH3
CH3
O
17-enanthoxyandrostene-4-one-3
Applied in same cases as testosterone propionate. Act slower but
longer as testosterone propionate. Enter by i/m way as 20% solution in
oil one time every 2-4 weeks. Included to the Testoenatum mixture
pro injectionibus amp. by 1 ml of 10% solution in peach oil (contains
24 mg of testosterone propionate and 111 mg of testosterone
enanthate).
Methyltestosterone (Methyltestosteronum)
CH3
OH
CH3
CH3
O
17α-methyl-17β-oxyandrostene-4-one-3
Synthetic testosterone replacement.
Characters. White crystalline powder, odorless. Practically not
soluble in water, slightly soluble in ether and oils, soluble in
acetone, easily soluble in ethanol.
Identification of methyltestosterone
On steroid system – Boscot’s reaction. Intense yellow
fluorescence.
2. At the dissolving of the drug in conc. H2SO4 orangeyellow color appears, and after adding of water orange-yellow color with green fluorescence (steroid
cycle).
3. On alcoholic group ОН – acetilation reaction, acting
of (СН3СО)2О in pyridine; at the dilution with water
select methyltestosterone acetate with melting
temperature 173-176º С (with decomposition).
4. On oxo-group in position 3 –the substance is boiled in
methanol with H2NOH*HCl – sediment of oxime falls
(melting temperature – 210-216ºС).
1.
Assay of methyltestosterone
UV-spectrophotometry at λ=240 nm.
Storage and application
In tightly corked container, protected from moisture
and light action.
Androgenic medication. In 2-3 times less active
than testosterone propionate, but remains activity
at the inside usage (sublingual).
Issue: tabl. by 5-10 mg.
Anabolic steroid structure means
Anabolic drugs called substance that in the body
stimulate the synthesis of proteins. Under their
influence increasing body weight, improves the
general condition of patients. By their structure
anabolic drug are similar to male sex hormones, which
have anabolic activity as side effect.
Apply of androgens with anabolic action is not
possible to treat women and children. Therefore it
became necessary to synthesize the substance, which
would be rather weak androgenic effect but a stronger
or equal with androgens anabolic activity. It turned
out that this can be achieved at some changes of
molecular structure of male sex hormones.
•
There are three major ways of androgenic activity
lowering :
1) Transfering of double bond from position 4 to position 5 :
CH3
5
2) Introduction of the additional double bond in position 1:
1
CH3
O
3) Elimination of methyl group at position 19.
Derivatives of 19-nortestosterone
are the best anabolic drug.
O
Methylandrostendiol
(Methylandrostendiolum) Methandriol*
CH3
OH
CH3
CH3
HO
17α-methylandrostene-5-diol-3β,17β or
3β,17β-dioxy-17α-methylandrostene-5
Characters. White crystalline powder, odorless. Practically not
soluble in water, soluble in ethanol, sparingly soluble in
chloroform.
Identification of methylandrostendiol
1.
2.
4.
5.
6.
At the dissolving of the drug in conc. H2SO4 orangeyellow color appears, with green fluorescence (steroid
cycle).
On alcoholic group ОН – acetylation reaction, after
the action of (СН3СО)2О in pyridine –17-monoacetate
of methylandrostendiol appears with melting
temperature –174-180º С.
To the solution of drug in 80% СН3СООН carefully
add conc. H2SO4 – on the border of phases appears
orange color, the upper phase is characterized by
yellow-green fluorescence.
UV- spectroscopy.
Specific optical rotation.
Assay of methylandrostendiol
Gravimetry.
Storage and application
In tightly corked container, protected from moisture and light
action.
By chemical structure resembles methyltestosterone, but has
weaker androgenic anabolic effect and stronger anabolic activity.
Apply at the disorders of protein metabolism after severe
injuries, operations, at the exhaustion, after infectious diseases, at
the lag growth in adolescents. Treatment of women should be
under the supervision of the gynecologist to prevent the effects
virilization.
Adopt in the form of tablets for sublingual absorption by 25-50
mg per day. Not used in prostate cancer, liver diseases.
Release in the form of tablets by 10 and 25 mg.
Methandrostenolone (Methandrostenolonum)
Анабол, Methandienone*
CH3
OH
CH3
CH3
O
17α -methyl-17β-oxy-1,4-androstanediene -3-one or
1,2-dihydromethyltestosterone
Characters. White crystalline powder, are allowed a weak
yellowish shade. Very little soluble in water, slightly soluble in
ether, easily soluble in ethanol, chloroform.
Identification of methandrostenolone
1.
2.
4.
UV-spectroscopy.
At the dissolving of the drug in conc. H2SO4 dark-red
color formed.
On oxo-group in position 3: after the interaction of the
drug
with
2,4-dinitrophenylhydrazine
2,4dinitrophenylhydrazone of methandrostenolonw formed,
which has orange-red color.
Test on purity
The presence of side steroids
as contaminant
(methyltestosterone) is established by TLC.
Selenium admixture (not more than 0,01%) - the method
of
combustion
in
oxygen
followed
by
spectrophotometry.
Assay of methandrostenolone
UV-spectrophotometry. In tablets methandrostenolone is detected
by photocolorimetric method by the interaction with conc. H2SO4 .
Storage and application
In tightly corked container, protected from moisture and light
action.
Androgenic action is in100 times weaker then in testosterone
propionate, anabolic activity – the same .
Apply at the protein metabolism disorder, chronic adrenal
insufficiency, toxic goitre, diabetic angiopathy, steroid
diabetes, chronic coronary insufficiency and myocardial
infarction, rheumatic heart lesions, atherosclerotic
cardiosclerosis, stomach ulcers and duodenal ulcers,
osteoporosis, bone fractures, eczema, psoriasis and others.
Produce in the form of tablets by 1 and 5 mg.
Phenobolin (Phenobolinum), Nerobolil,
Durabolin, Nandronolone phenylpropionate*
CH3
OCOCH2CH2C6H5
O
17β-phenylpropioneoxy-19-norandrostene-4-one-3 or
19-nortestosterone phenylpropionate
Characters. White, sometimes with a creamy tinct crystalline
powder. Practically insoluble in water, slightly soluble in ethanol,
freely soluble in chloroform and acetone.
Identification of phenobolin
1.
2.
3.
Melting temperature (95-99 °С).
IR-spectroscopy.
TLC.
Assay
UV-spectrophotometry.
Storage and application
In tightly corked container, protected from light action.
Phenobolin –active anabolic mean with long action (7-15
days after single injection). Detects very weak androgenic
effect, in women virilyzation phenomena almost not
observed. Applied in those cases, as methandrostenolone,
not used for the treatment of prostate cancer.
Enter by the i/m way in oil solution by 25-50 mg 1 time
every 7-10 days.
Issue: by 1 ml of 1% and 2,5% solutions in oil.
Retabolil (Retabolilum), Nandrolone
CH3
O
OCO(CH2)8CH3
17β-decanoyloxy-19-noradrenostene-4-one-3 or
19-noradrenostene decanoate
Strong and long (3 weeks) anabolic effect. Low toxicity, androgenic
effect is lover than in phenobolin. Enter by the i/m way by 25-50
mg 1 time every 2-3 weeks. Produce in the form of 5 % oil solution
in amp. by 1 ml.
Female sex hormones and synthetic
substitutes
Female sex hormones called estrogens (from the Greek word
"estrus" - estrus and "Gennao" - birth). These hormones are
produced in maturing ovarian follicles and participate in the
implementation of menstruation. They are necessary for the
formation of female sex and female secondary sexual
characteristics and functions for having children.
The natural estrogen is estradiol and estron. Among them estron is
a medical drug and estradiol used in the form of esters and other
derivatives, becouse estradiol itself very rapidly inactivates in the
body.
As medical drugs estrogens are used in low ovarian function
(primary and secondary amenorrhea), underdevelopment of the
uterus, sterility, post-castartion disorders, surgical removal of
ovaries. Estrogens are used to treat parahormone cancer in men and
increased of labor activity (causing contraction of the uterus).
Do not apply to women aged up to 60 years for malignant and
benign tumors of the genital organs and mammary glands.
Earlier estrone (folliculine) and estradiol are obtained from
the urine of pregnant women, then - from the urine of
pregnant animals. Now them are obtained synthetically
from cholesterol.
Estrone
CH3
O
Estradiol
CH3
HO
HO
OH
Chemical signs of estrogens
1.
CH3
12
11
13
16
1
10
2
9
14
8
3
7
5
4
2.
17
6
Estrane
15
3.
4.
Derivatives of estrane.
Presence of the tree double
bounds in the positions 1, 3,
5(10).
Group –ОН (oxy-group) in
position 3.
Group –ОН (can be
esterificated) or oxo-group
(=О) in position17.
General identification reaction on
estrogenic hormones
On steroid system: Boscot’s reaction and reaction with
concentrated sulfate acid.
Esters of estrogenic hormones (estradiol dipropionate):
hydrolysis with the following identification of the
products of hydrolysis; hydroxamic reaction.
Phenolic hydroxyl - reactions:
а) electrophilic substitution (bromination, nitration,
formation azo-dye, aurin stain);
b) salt and complex formation with heavy metals salts (for
example, FeCl3);
c) Esters formation (for example, with benzoyl chloride),
which have character melting temperature.
Estrone (Oestronum) Folliculine
CH3
O
HO
3-oxyestratriene-1,3,5(10)-one-17
Characters. White crystalline powder. Practically
insoluble in water, soluble in ethanol and ether, easily
soluble in chloroform.
Identification of estrone
1. Boscot’s reaction – green fluorescence appears.
2. Estrone solution in conc. H2SO4 ). has golden-yellow
color with intense green fluorescence (steroid cycle).
3. At the interaction with NH2OH*HCl oxime precipitate
falls (with melting point 228-233ºС).
4. At the interaction with з diazoreagent formation of azodye is observed (reaction on phenolic hydroxyl).
5. At the action of C6H5COCl phenolic hydroxyl
esterificates and formed ester has melting temperature
of 220ºС.
Activity of estrone determined biologically (evocation
of oestrus) in neutered female mice and rats. In 1 mg
are 10000 UA.
Assay of estrone
Polarimetry (solution of the drug in dioxane).
Photocolorimetry (by the reaction of azo-dye formation).
Storage and application
In tightly corked container, protected from light action.
Enter by the i/m way in the form of oil solutions at the
low ovarian function (primary and secondary
amenorrhea), infertility, cancer and underdevelopment
of secondary sexual characteristics, overterm pregnancy,
the surgical removal of ovaries.
Issue: amp. by 1 ml of 0,05% or 0,1 % oil solution.
Estradiol dipropionate * (Oestradioli
dipropionas)
CH3
OCOC2H5
C2H5OCO
3,17-dipropioneoxyestratriene-1,3,5(10)
Characters. White crystalline powder. Practically insoluble in
water, very little soluble in ethanol and oils.
Identification of estradiol dipropionate
1. IR- and UV-Spactroscopy.
2. At the Boscot’s reaction green fluorescence appears.
3. At the heating with conc. H2SO4 there is a brown
coloration, which by dilution with water and heated
changes to pink.
4. On esteric groups conducted hydroxamic reaction
(look testosterone propionate).
5. At the hydrolysis by КОН in ethanol estradiol forms,
which falls in the form of precipitate at the dilution
with water and acidification by НСl. Melting
temperature of estradoil is 177 ºС.
6. Propanoic acid, which formed after the acidic
hydrolysis, can be identified by the reaction with
ethanol - ester formed, which has a characteristic odor.
CH3
OCOC2H5
CH3
OH
2H2O
H2SO4
C2H5OCO
HO
C2H5COOH + C2H5OH
C2H5COOC2H5 + H2O
+ 2 C2H5COOH
Assay of estradoil dipropionate
Alkalimetry, the reverse titration. Substance is
hydrolyzed alcohol by the alcoholic solution of
potassium hydroxide, an excess of which is titrated
by hydrochloric acid solution by phenolphthalein, Ем
= ½ М.m.
CH3
OCOC2H5
CH3
OH
+ 2 KOH
+ 2 C2H5COOK
HO
C2H5OCO
KOH + HCl
KCl + H2O
Storage and application
• In tightly corked container, protected from light action.
• In two times more active than estrone, has a strong and
prolonged effect, apply in those cases, as estrone. Enter by
i/m way by 1 ml of 0,1% solution in oil every 1-2 days.
• Estradiol
is
a
part
of
the
following
preparations“Estramone” (transderm. plaster, 4 mg 20 cm2
№6); “Estrogel” (gel for the local usage 0,6 mg/g 80 g);
“Estrimax” (tabl. 2 mg №28).
• Complex preparations – “Pausogest” (estradiol
hemihydrate and norethisterone acetate); “Climodiene”
(estardiol valerate and dienogest).
• Estriol is a part of “Ovestine” (tabl., vag. cream, vag.
suppos.).
Ethinylestradiol (Aethinyloestradiolum)
Ethynilestradiol*
CH3
OH
C
CH
HO
17α-ethinylestratriene-1,3,5(10)-diol-3,17β
Characters. White or creamy white fine crystaline powder,
odorless. Practically insoluble in water, slightly soluble in alkali,
soluble in alcohol, chloroform, soluble in acetone, ether and
dioxane.
Identification of ethinylestradiol
IR- and UV-spectroscopy, TLC
To detect ethynil group substance is dissolved in
H2SO4, add FeNH4(SO4)2 solution – reddish-brown
precipitate falls after the dilution with water pinkred sediment falls.
3. At the Boscot’s reaction orange fluorescence
appears, in 50-100 times stronger than estrone
fluorescence.
4. At the action of conc. H2SO4 orange-red color forms
with yellow-green fluorescence .
5. At the interaction with benzoyl chloride
ethinylestradiol-3-benzoate forms with melting
temperature of 199-202ºС (phenolic hydroxyl).
1.
2.
CH3
OH
C
CH
O
+
C
Cl
CH3
HO
OH
C
O
C
CH
+ HCl
O
Assay of ethinylestradiol
1. Alkalimetry by the substituent(look pregnine).
2. Spectrophotometry or photocolorimetry by the
formation of bis-diazocompound in alkaline medium at
the interaction with diazoreagent :
Ethinylestradiol is stored in tightly corked container in a
dark place.
Application of ethinylestradiol
Ethinylestradiol - one of the most active estrogenic agents.
Introduction of ethinyl residue to the estradiol molecule
increases stability and activity, that is why ethinylestradiol is
taking internally.
Apply at the hypogenitalizm (primary amenorrhea,
underdevelopment of the uterus), ovarian hypofunction and
secondary amenorrhea by 0,05-0,1 mg; for elimination of
neuro-vascular disorders of estrogenic insufficiency
receiving by 0,01-0,02 mg per day; to treat cancer prostate
and breast cancer in women over 60 years - to 3 mg per day
over a long time. In the treatment of prostate cancer in men
may be feminization.
Issue: tabl. by 0,01 and 0,05 mg under the “Microfolin” and
“Esterlan”.
Is a part of oral contraceptive preparations.
Synthetic steroidal structure estrogens
Substances that have estrogenic activity, were found not only
among the steroid, but in some aromatic compounds.
Admitting that the effect of estrogen depends on the presence
of aromatic nuclei in the molecule.
Important role belongs to hydroxyl and keto-groupsgroups
that can form hydrogen bonds and interact with proteins in the
body.
For the detection of estrogenic action is important the distance
between the functional groups. It is determined that the
distance between the hydroxyl groups (in position 3 and 17) in
estradiol is 1,1 nm, in meso-form of synestrol 1,2 nm, in the
trans-isomer of diethylstilbestrol – 1,22 nm. At the same cisisomer of diethylstilbestrol, in which the distance between the
hydroxyls is 0,75 nm, is physiologically inactive.
The formation of ethers and esters do not reduce estrogen
activity, but increases the period of action.
Synestrol (Synoestrolum)
Hexestrol
C2H5
HO
H
C
C
H
OH
C2H5
Meso-3,4-di-(p-oxyphenyl)-hexane
Characters. White crystalline powder, can have a yellowish
tint, odorless. Practically insoluble in water, soluble in ethanol,
chloroform, vegetable oils, alkali solutions.
Estrogenic activity of synestrol is equal to estrone activity. Is
used for the treatment of those diseases as estrone.
Issue: tabl. by 1 mg; amp by 1 ml of 0,1% and 2% oil
solutions.
Diethylstilbestrol
(Diaethylstilboestrolum)
C2H5
HO
C
C
OH
C2H5
Trans-3,4-di-(p-oxyphenyl)-hexene-3
Characters. White crystalline powder, odorless.
Practically insoluble in water, soluble in ethanol, ether, vegetable
oils, alkali solutions.
Two times more active than estrone, but due to the side effect it is
used only for the treatment of breast cancer in women older than
60 years.
Issue: amp. 3% oil solutions by 1 ml.
Identification of synestrol and
diethylstilbestrol
1. At the interaction of synestrol chloroform solution with conc.
H2SO4 (In the presence of formalin) chloroform layer is painted in
a cherry-red color (phenyl radicals). Diethylstilbestrol solution in
conc. H2SO4 has the orange color, which gradually disappears after
the dilution with water.
2. When you add bromine water solution to synestrol in conc.
СН3СООН yellow precipitate forms. Diethylstilbestrol with
bromine water in the presence of liquid phenol at the heating forms
the emerald-green color, after adding of few pieces of sugar and
heating coloration turns into dark blue, and cherry-brownish.
3. At the adding of to the synestrol chloroform layer FeCl3 solution
and pyridine – there is a blue coloration, which by the adding of
pyridine in excess turns green. Alcohol solutions of
diethylstilbestrol colored in green, which gradually turns into
yellow (phenolic hydroxyl).
4. At the interaction of drugs with (СН3СО)2О or С6Н5СОСl
diacetates (dibenzoates) form, which have characteristic
temperature of melting.
Assay of synestrol and diethylstilbestrol
1.
Method of acylation. Based on the obtaining of esters (diacetyl
derivatives) by heating with acetic anhydride in the presence of
pyridine. Excess of (СН3СО)2О is transformed to СН3СООН and
titrate acid by NaOH solution, indicator - phenolphthalein, Еm = ½
М.m. In parallel control experiment is conducted:
2. Assay of synestrol in oil solution is conducted solution
after the extraction by aqueous solution of sodium
hydroxide by the reverse bromatometry method with
control experiment, Еm = 1/8 М.m.:
KBrO3 + 5KBr + 6HCl
3Br2 + 6KCl + 3H2O
C2H5
HO
CH
Br
CH
4Br2
OH
C2H5
Br
C 2H 5
HO
CH
CH
OH
C2H5
Br
Br2 + 2KCl
I2 + 2Na2S2O3
I2 + 2KBr
2NaI + Na2S4O6
Br
4HBr
3.
Synestrol and diethylstilbestrol can be determined by photometric
method by the reaction of azoconnection with diazotated
sulfanilic acid:
N
C2H5
HO
CH
CH
OH
N
2
HSO4
C2H5
SO3H
C2H5
HO
HO3S
N
CH
N
CH
OH
C2H5
N
N
SO3H
2H2SO4
Storage of synestrol and siethylstilbestrol
In tightly corked container, protected from light action.
Prostaglandins
Prostaglandins - biologically active substances that are contained
in various organs and tissues (blood, lung, kidney, intestine,
uterus, etc.). They are a sort of intracellular hormones that have
influence on many body functions . Produced in the body in very
small quantities (about 100 micrograms per day). Most
accumulate in the seminal fluid.
The first data was in 1913, when from the male prostate extract
was isolated, which puts down AP in dogs .
Discoverer of prostaglandins is the Euler (Sweden), who
investigated these matters since 1934 year. He proposed the term
"prostaglandins" that is from the Latin name of the prostate gland
(Glandula prostata).
Like vitamins, prostaglandins are divided into groups with
similar chemical structure. Each one has a Latin index E, F, A, B
(abbreviated writing PGE, PGF, PGA, PGB).
Prostaglandins - a compounds without azot, in the base of its
structure is prostanoic acid:
Individual prostaglandins
distinguish by the number and
placing of radicals (Hydroxyl,
carboxyl) and double bonds
in the molecule.
Extraction of prostaglandins
1. Extraction from animal sources (semen body fluids, animal
tissue, etc.). The method is laborious, long and expensive.
2. Biosynthesis of precursors - polyunsaturated fatty acids in the
presence of appropriate enzymes. Almost biosynthesis is
conducted by incubation of unsaturated fatty acids from
homogenate tissues of cattle (mostly seminal glands).
3. Synthetic methods for prostaglandins extraction include up to
29 stages. It is difficult to provide the necessary isomers that
have biological activity.
Characters
Selected as individual compounds prostaglandins - a white crystalline
substances which are easily dissolved in organic solvents.
To study the chemical structure of prostaglandins UV, IR, NMR
spectroscopy, mass-spectrometry, X-ray analysis are used.
Identification
For the analysis of prostaglandins are widely used various types of
chromatography: column, paper, thin layer, gas-liquid (GLC) and
others. Especially effective for the quantitative analysis is
combination of GLH and mass-spectrometry that allows to detect 9-10
g of prostaglandins.
For quantitative determination UV-spectrophotometry are used.
To evaluate the physiological activity and the content of
prostaglandins in the tissues biological methods are used, which are
based on their ability to affect on the smooth muscles (stomach,
intestine, uterus), blood pressure and other functions. Use also
enzymatic and radioimmunological methods of analysis.
Usage of prostaglandins
Prostaglandins affect on the contractile activity of smooth
muscle, functions of the nervous and cardiovascular systems,
blood circulation, support the tone of urinary tract and bladder,
and exhibit bronholitic bronhodilatation action, involved in the
inflammation processes.
The most active groups of prostaglandins are E, F and A.
Prostaglandins E1 and E2 affect on the function of the bronchi;
PGE inhibits the secretion of gastric juice; PGE and PHF cause
reduction of uterine muscle; PGA1 and PGA2 during the action
on blood vessels, make lower a blood pressure .
Various pharmacological activity of prostaglandins hampering
their practical application in medicine, so it is nessesary to search
their synthetic analogs, which are available obtained and are
selectively derived on the specific systems and functions.
Obtained in the present analogs contain in the molecule structure
cyclopentane nucleus and are 7-oxyanalogs, 15-ketoanalogs,
contain esteric group at the positions 1 and 15. Some analogues
contain instead of cyclopentane other cycles, and shortened or
elongated alkyl chains.
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