Pharmacognosy

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Pharmacognosy for Doctor of Pharmacy I
Natural Products Biosynthetically Derived from
Acetate
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STEROIDS
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• STEROIDS
• isoprene 6 units
• triterpenoids - lack dimethyl at C-4
• cyclopentanoperhydrophenantrene
• -tetracyclic ring system-
• ring A, B, C -

chair conformation
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The biosynthesis of steroids
squalene epoxidase
squalene
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oxidosqualene squalene-2,3-epoxide
proton-induced cyclization
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carbonium ion
cycloartenol cyclase
found in photosynthetic organisms higher plant,
algae
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cycloartenol
precursor ??? steroid ?????
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carbonium ion
lanosterol cyclase
found in non-photosynthetic organisms animal,
fungi
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lanosterol
precursor ??? steroid ???????, fungi gtgtgt
demethylation at C-4, C-14
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phenanthrene
steroid nucleus
cyclopentanoperhydrophenantrene
ring junction A/B - trans or cis
B/C - trans C/D trans
(except C.G.)
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Steroids numbering
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Chair conformation
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A
B
trans junction
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cholestanol
5a-H
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cis junction
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coprostanol
5b-H
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Systematic steroid nomenclature - based on a
series of parent hydrocarbon
androstane C19 androgen testosterone
estrane C18 estrogen
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pregnane C21 progesterone
cholane C24 bile acid
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24
cholestane C27 cholesterol
ergostane C28 ergosterol (24-CH3-cholestane)
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24
stigmastane C29 stigmasterol (24-ethylcholestane
)
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bufanolide C24 bufadienolide
cardanolide C23 cardenolide
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Classification of steroids

• sterols
• vitamin D
• bile acids
• steroidal hormones
• steroidal saponins
• steroidal alkaloids
• cardiac glycosides

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I. STEROLS

• 27-29 carbon atoms
• aliphatic side chain at C-17
• b-hydroxy group at C-3
• ring A/B trans junction
• zoosterol, phytosterol, mycosterol

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Zoosterols C27
cholesterol
principal animal sterol constituent of cell
membrane human gallstones precursor of steroid
hormones, vitamin D an bile acids
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sources brain spinal cord of cattle,lanolin
Ovis aries ???? Bovidae
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Lanolin (fatty material coating sheeps
wool) complex mixture of esters of long chain
fatty acids with aliphatic alcohols and sterols
saponification
wool alcohols (lanolin alcohols) 34cholesterol 38
lanosterol/dihydrolanosterol
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wool fat (anhydrous lanolin) hydrous wool fat
(lanolin) wool fat 70 water absorbable
ointment base
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Phytosterols C28-29
b-sitosterol stigmasta- 5-en-3b-ol
stigmasterol stigmasta- 5,22-dien-3b-ol
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Glycine max
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Papilionaceae
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Plant sterol esters obtained by esterifying
sitosterol from soya beans with fatty acids
to produce a fat-soluble product
dietary plant sterols 1.3 g/day
reduced blood LDL cholesterol (decreasing
intestinal cholesterol absorption)
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Mycosterols
ergosterol
ergosta-5,7,22-trien-3b-ol provitamin D2
14-demethylation
Lanosterol ergosterol
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Fusidic acid a steroidal antibiotic fungus,
Acremonium fusidioides (Fusidium
coccineum) and Cephalosporium spp. against
gram positive bacteria penicillin-resistant
Staphylococcus, especially osteomyelitis
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24S
stigmastane 24R-ethyl-cholestane poriferastane
24S-ethyl-cholestane poriferasterol (green
algae)
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24S
ergostane 24S-methyl-cholestane campestane
24R-methyl-cholestane campesterol (Mosses)
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• Sterols of marine invertebrates
• Dinoflagellate
• Algae Fucus spp. - fucosterol
• Porifera
• Coelenterata
• Echinodermata
• Mollusca

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crustecdysone
ecdysone from crustacean (Arthropoda)
2b,3b,14a,20,22-pentahydroxy-
5b-cholest-7-en-6-one
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• ecdysteroids
• polyhydroxysteroids
• cis-fused A/B ring junction
• 14a-hydroxy-7-ene-6-one system
• exhibit physiological activities as
• moulting hormones of insects and
• crustaceans

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• II. Vitamin D
• regulates the calcium and
• phosphate balance
• promote absorption of Ca2 PO4-
• from the small intestine
• is an essential factor in bone
• formation
• (a deficiency causes rickets
• and osteomalacia)

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vitamin D
vitamin D2 (ergocalciferol) 9,10-secoergosta-5,7,
9(10),22-tetraen-3b-ol
vitamin D3 (cholecalciferol) 9,10-secocholesta- 5
,7,10(19)-trien-3b-ol
plants yeasts
animals
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vitamin D2, D3 gtgtmetabolic hydroxylations in body
to yield molecular forms with greater physiologic
al activity 25-OH -cholecalciferol (liver)
1,25-di-OH-cholecalciferol (kidney)
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Cod liver oil Gadus morrhua (Gadidae) contain
fish oil about 50 (fixed oil)
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Production of cod liver oil rotting process
--allowed to rot and skimmed off steaming
process --the oil is released from the tissue
refining
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• Impurities separation
• under air-free condition to avoid oxidation
• the crude oil is rapidly heated at 77oC
• centrifuge to separate the liver tissue and
• water
• Drying
• in vacuum drying to evaporate the residual
• water
• Winterization
• are cooled at 0oC and filtrated to separate
• stearin

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• Deoderization
• is achieved by steaming to remove
• aldehydic and ketonic impurities
• Standardization
• standardized for vitamin content
• unsaturated fatty acid 85,
• saturated acid 15
• vitamin A and D

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Allied drug ??????????????????????? Halibut
liver oil Hippoglossus vulgaris (H.
hippoglossus) Shark liver oil Hypoprion
breoirostris
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Calcipotriol and tacalcitol topical treatment of
psoriasis inhibit the cell proliferation Vitamin
D2 also employed as rodenticide caused fatal
hypercalcaemia
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III. Bile acids C24 cholane skeleton
cis-fusion of ring A/B 5b-H 3a- and
7a-hydroxyl groups C5-carboxylic acid
side-chain occur in salt form in bile act as
detergents degrade from cholesterol
(eliminate excess cholesterol)
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typically bound via an amide linkage to
glycine or taurine
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Cholic acid Chenodesoxycholic acid
(primary bile acid formed in liver)
7a-deoxygenation Desoxycholic
acid Lithocholic acid (secondary bile
acid intestinal flora)
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emulsify fats and encourage digestion eliminate
excess cholesterol if not gallstone
disease
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Ox bile extract Bos taurus (Bovidae) contain
sodium glycocholate and sodium
taurocholate use as choleretic drug emulsifying
agent dispersion and absorption of lipids
and fat-soluble vitamins modulation of
cholesterol synthesis elimination of
cholesterol (solubilize cholesterol in bile and
promote intestinal cholesterol excretion)
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Bos taurus
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Chenodiol and Ursodiol (7b- OH)!!! cholesterol
gallstone dissolution (cholelitholytic) was
not effective for radio-opaque gallstones
(contain calcium) inhibit HMG-CoA reductase
the cholesterol content of the bile
cholesterol gallstone formation reduce net water
absorption and cause diarrhea dose-related
hepatoxicity lithocholic acid
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Steroidal hormones 1. Sex hormones estrogens
(estrane group) estradiol 3,17b-OH
estratriol 3,16a,17b-OH
estrone 3-OH-17-one
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progestins (pregnane group) progesterone
4-ene-3,20-dione androgens (androstane group)
testosterone 17b-OH-4-en-3-one replacement
therapy of male hypogonadism treatment of
impotence treat metastatic breast cancer and
postpartum breast pain
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2. Adrenocorticosteroids mineralocorticoids
(pregnane group) aldosterone - Na, K
and water balance
glucocorticoids (pregnane group) cortisone,
hydrocortisone anti-inflammatory (RA,
allergic, asthmatic disorder),
immunosuppresant, lifesaving for pt. in
anaphylactic shock.
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• The biosynthesis of steroid hormones
• ????????????????????????? steroid hormones
• Solasodine (steroidal alkaloid)
• Solanum
• Hecogenin Agave
• Stigmasterol Glycine
• Diosgenin Dioscorea, Costus,
• Trigonella

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????????? steroid hormones ???
diosgenin ??????? glucocorticoids ???
microbial transformation