Download Sheet #12 Medicinal Plants

Medicinal plants
Dr Fatima Afifi
Lec no. : 12 lec
pharm D : Lina Msllam
The word ene means presence of unsaturated
Last time we were talking about antibiotics
lctone ring.
originating from acetate malonate glycosidic
derivatives which we divided to 3 groups: fused
rings, macrolides and polyenes. Today we will
continue with the last one of antimicrobial agents
which is polyenes which is an antifungal agents.
Last time we said that Griseofulvin which is a
Polyenes are divided according to no. of
conjugated double bonds, so we have : heptaene
,pentaene , hexa, tetra .. etc
Amphotericin B :
fused ring antibiotic possessing antifungal
It has 7 conjugated double bonds so it’s a
activities.
heptaenes.
The polyenes are similar in their structure to
Notice no. of conjugated DB isn’t the same as no.
lactone antibiotics for having a very huge lactone
of DB - e.g:
ring.(20-44 membered)
Lactone ring usually has different types of
Nystatin A have 6 DBs but it’s considered
tetraene cuz it has only 4 DB as conjugated ones.
substitutions; hydroxyl group mainly, but it could
have glycosidic linkage, methyl group and it could
have in its moieties an amino sugar.
So these are the similarities between
polyenes but what are the differences btween
them ?
They differ in the no. of unsaturation in their last
So the largest no. of DB is necessary to classify
these compounds.
lactone ring. And that distinguishes them from
Amphotercin B and cannabicidin are both
macrolide antibiotics which don't have any
hepatenes which are used for fungal infections,
unsaturation in them.
specially life threatening ones due to long term
streptomyces are the usual producing organisms,
there are around 200 hundred different types of
polyenes isolated but only few of them could be
use of tetracycline that cause elimination of
normal flora, so there will be outgrowth of fungal
infection .
used as antifungal with restrictions due to high
Candida Albican is the main m.o that causes this
toxicity.
infection.
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Medicinal plants
Dr Fatima Afifi
Lec no. : 12 lec
pharm D : Lina Msllam
Amphotericin B and cannbicidin used to treat
Antineoplastic Anthracyclin compounds have
disseminated fungal infection by oral and IV. But
broad spectrum of activity, and are used as
standard or synthetic compounds, such as:
the tetraenes like natamycin and nystatin A are
used for other antifungal infections ;mainly skin
infection and vaginal infections in topical route .
Doxorubicin is one of the most used anti-tumors
and have broad spectrum of activity. The
anticancer potential is high in isolated and
synthetic compounds.
Nystatin A & natamycin are also used as eye
drop to treat viral infecton in the eye.
Erythromycin A is a macrolide antibiotic with
uncommon sugar linkage.
Adding a sugar linkage is the last rxn of
microsynthesis.
Amphotericin B have acteyl Co A and 15 malonyl
Doxorubicin have high potency as newly
CoA & 3 methylmalonyl Co A added with the
synthesized cpd (compound) and is used as anti-
presence of different methyl groups in the
tumor.
macrolactone ring.
It’s also used as positive standard to check the
The color of lactone compounds isn’t intensive
potency of newly synthesized anticancerous
due to high no. of polyenes (no. of conjugated
agents.
bonds), its usually in light yellow appearance with
various shapes not a white crystalline structure..
Naturally antibiotics and anticancer products from
plants origin are Tested in 6 different patterns for
Another member of acetate malonate pathway
their potency, if it was +ve result they will be
are anticancer agents : compounds having
isolated.
polycyclic structure, they have antineoplastic
activity and can be used to treat breast cancer
,childhood tumor, types of adenomas and cystic
liver carcinoma.
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Daunorubicin was isolated before and gained
success in solid tumors , but few years later they
discovered Doxorubicin which took lead due to
higher potency.
Medicinal plants
Dr Fatima Afifi
Doxorubicin is the oxidized form of Daunorubicin ,
Lec no. : 12 lec
pharm D : Lina Msllam
This was all about Anthracyclisn.
These two cpds have identical structures only
differing in their side chain, we have methyl group
in Daunorubicin while there's hydroxymethyl
group in doxorubicin.
-NOW we move to shikmic acid
pathway :
Hybrid substances like c6- c3 cpds of phenyl
propane derivatives have been isolated by
Epirubicin: differ in the sugar moiety.
Chinese scientists .
At 1885 they discovered the shikimic acid
The rest of cpds ( in slides) are similar only differ
pathway :
in methyl group or hydroxymethyl groups.
Anticancers and antibiotics tend to produce
Illicium anisatum: Shikimino is a Japanese name ,
analogues so they are more reasonably modified,
it got its fame as a C6 –C3 acid material, that is
one example:
starting to make Tamiflu (drug for flu) which is
They have uncommon glycosidic sugars
Doxorubicin modified to Epirubicin which differ
only in their stereochemistry of hydroxyl group of
the sugar moiety at 4 prime.
A Semi synthetic cpd of Daunorubicin is the
highly demanded .
So larger amounts are needed, and they did that
by genetic engineering; enzymes were
transferred to E.coli.
This is an easy way to make it because these m.o
Idarubicin, differing in presence of methoxy grp,
are cheap and produce it quickly, its biochemistry
daunorubicin was discovered in 1966, while
is well studied, and known due to gene isolation
dexarubicin1969.
from plants and if we put it in larger mo than
Regardless of their origin from plants or MO, they
E.coli we get more amounts like in streptomyces.
have important adverse effects which is
unfortunately bone marrow suppression, which
we can get 100 kilos !!
causees new complications, and they are used in
Shikimic acid is sometimes used as obligatory
their IV route to be given in hospitals or for
intermediate or raw material and therapeutic
restricted studies in biochem labs.
agent:
They also cause GI disruptions, nausea and
vomiting, lose of appetite and loss of hair.
•
Important for aromatic compounds
production.
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Medicinal plants
Dr Fatima Afifi
•
Precursor of aromatic amino acids
group shikmic acid which is mono unsaturated
(Phenylalanine, Tyrosine, Tryptophan)
cyclohexane carboxylic acid.
biosynthesis in bacteria, fungi & higher
plants.
•
Lec no. : 12 lec
pharm D : Lina Msllam
Building block for other compounds:
certain alkaloids, coumarins, phenyl
propanes, vol. oils,..
•
Starting point for tannins in all plants
•
Provide protection of plants against
micro-organisms .
Phenylalanine is turned to tyrosine in our body by
oxidation, tyrosine differs from phenylalanine by
only having para-hydroxyl group
Tryptophan is v. important and produces many
huge compounds of alkaloids.
Now we will discuss biosynthesis:
Shikimic acid & acetate malonate produced from
CHO have the same pathway for introducing
terminal cpds.
Many minor rxns which eliminate water can bring
many new derivatives… carbonyl group can be
easily reduced to hydroxyl group: e.g: Dehydro
shikimc acid with mono unsaturated cyclohexane
carboxylic acid can be reduced to its hydroxyl
function.
Quinic acid is also needed to precede synthesis
as obligatory intermediate
All of these rxns are reversible not one way and
progress on the direction of demand.
While shikimic acid is the Obligatory intermediate
in these rxns we should be able to incorporate
Refer to slide no. 3 in shikimic acid pathway
radioactive shikimic acid to the pathway as a sign
slides.
that shikimic acid is involved.
Shikimic acid forms Chorismic acid: at slide 4
shikimic acid is considered as a precursor for
huge classes of biosynthesis , shikimic acid is
obtained from 2 CHO cpds :
Phosphoenol pyruvate 3 Carbon sugar with a 4
carbon sugar erytrhose -4- phosphate giving a
heptulose to 3-dehydroquinic acid which is a
carboxylic acid that is easily reduced to hydroxyl
choriso (greek means splitting)
Before breaking down chorismic acid have two
options :
1- Form prephinic acid with its derivatives parahydroxy phenylpyruvate and phenylalanine
2- Anthranilic acid with its derivative tryptophan
based on the indole nucleus.
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Medicinal plants
Dr Fatima Afifi
Lec no. : 12 lec
pharm D : Lina Msllam
Tryptophan makes different alkaloids depending
on the type of indole nucleus that’s present, such
as indole acetic acid.
Indole Acetic acid is a component of growth
promoting hormones produce several synthetic
analogues, like indole usinic acid which we will
talk about in coumarins.
From the prephinic acid pathway we have phenyl
pyruvate which has ketoacids that are liable to
amination rxns and Phenyl alanine that is
obtained from glutamine, which can be converted
to cinnamic acid, and it differs from tyrosine only
in the presence of hydroxyl group in the para
position.
Converted to different aromatics depend on the
presence of a.as.
Tyrosine will be converted to para coumaric
acids, while Phenylalanine is converted to
Because there are many acids with processed c3c6 backbone, they are termed as cinnamic acid,
para hydroxy Cinnamic acid & 3,4 dihydroxy
cinnamic acid which is caffeic acid, they belong to
the class of cinnamic acid regardless of
substitution.
Also due to the presence of many C6- C1 acids
like hydroxybenzoic acid and methoxybenzoic
acid, they are termed as benzoic acid regardless
of substitution.
These C6-C3 cpds can be transferred from cis to
trans cinnamic acid easily, specially hydroxycinnamic acid, the nature favors the trans position
in both coumarins and cinnamic acids.
Another characteristic of c3-c6 cpds is:
cinnamic acid through eliminating amino group by
If there is one substituent of aromatic ring it is on
transaminase rxn.
para position to the side chain, if there are more
They are precursors for different aromatic
alkaloids.
so this pathway provide cinnamic acid
First substitution is usually in para position.
than one it will be on different positions, if it's in
orthro position we will discuss it later on in the
coumarins.
Biosynthetic pathways have different possibilities
1-Substitution in aromatic ring: we have
parahydroxy, methoxy, 3,4-dihydroxy, (3,4,5trihydroxy) dreivatives. So we get cinnamic acids
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Medicinal plants
Dr Fatima Afifi
Lec no. : 12 lec
pharm D : Lina Msllam
having different substitution pattern of their
So two rxns happen simultaneously, we eliminate
aromatic ring.
the original carboxyl to get a new compounds.
2nd possibility : stage of oxidation of side chain: in
cinnamic acid hydroxyl group can be obtained
Therefore shikimic acid is used for making
phenolic cpds.
from their corresponding hydroxy-methyl
We get phenolic substances regardless if the
derivatives to obtain v. important class which is
precursor have carboxyl group from the beginning
alcohols: like polyphenyl alcohol. We modify
or not, because it will be introduced to it.
them by reduction to aldehyde, completely
saturated CH3 or unsaturated, depending on the
position of the side chain we get allyl side chain
So shikimic acid is responsible for making
phenolic cpds.
or propane side chain as derivative of the acid so
you have in your sheets names of different
we have big no. of acids, alcohols …etc.
substituted cinnamic acids so refer to them.
3rd possibility: Shortening of the side chain
THE END
Reducing no. of carbons from C6 –C3  C6- C1
 C6. We can eliminate 2 carbons but from what
origin?
From the acetate we eliminate it by Beta oxidation
.to get a resembling benzoic acid having the
same substituents: parahydroxy, methoxygroup
3,4 dihydroxy or (3,4,5-trihydroxy).
Shikimic acid responsible for production of
phenolic substances, so we must have a phenyl
hydroxy group.
To get rid of carboxyl group, the compound
should undergo decarboxylation.
Decarboxylation of dihydroxy benzoic acid
actually happens by Oxidative decarboxylation,
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