1. 7/19/2012
By- Jitendra Bhangale
Assistant Professor & Head,
Department of Pharmacology,
Smt N. M. Padalia Pharmacy College,
Ahmedabad
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© 2010 Delmar, Cengage Learning
Chemotherapy: The use of synthetic
chemicals to destroy infective agents. Also
applied to inhibit growth of malignant or
cancerous cells within the body.
Antibiotics: Substances prduced by some
microorganisms to kill or inhibit the growth of
other organisms.
By Jitendra Bhangale
Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad2
© 2010 Smt N. M. Padalia
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2. 7/19/2012
Prokaryotes: Cells without nuclei
e.g. bacteria
Eukaryotes: Cells with nuclei e. g. Protozoa
unicellular, Helmints multicellular
Viruses even though they are not cells at all
Cancer cells are also foreign or parasites
but are more similar to normal host cells
than any other categories.
By Jitendra Bhangale
Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad3
© 2010 Smt N. M. Padalia
Class I: The utilization of glucose or some alternative
carbon source for the generation of energy and some
carbon compounds.
Class II: the utilization of the energy and precursors to
make all necessary small molecules : amino acids,
nucleotides, phospholipids, amino sugars,
carbohydrates and growth factors.
Class III: Assembly of the small molecules into
macromolecules: proteins, RNA, DNA, polysaccharides
and peptidoglycan.
By Jitendra Bhangale
Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad4
© 2010 Smt N. M. Padalia
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3. 7/19/2012
Class I reactions are not promising targets.
There is no difference between bacterial and
human cells.
Even if glucose pathways were to be
blocked, a large variety of other compound
could be used by bacteria as alternatives.
By Jitendra Bhangale
Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad5
© 2010 Smt N. M. Padalia
Class II reactions are better targets.
Some pathways involved in class II reactions
exist in parasitic but not in human cells.
Pathways may be identical but there may be
differential sensitivity to drugs.
Folate synthesis is an example of metabolic
pathway found in bacteria but not in man.
By Jitendra Bhangale
Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad6
© 2010 Smt N. M. Padalia
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4. 7/19/2012
Class III reactions are particularly good
targets for selective toxicity, because every cell
has to make its own molecules that cannot be
picked from the environment.
Examples:
Peptidoglyan synthesis
Protein synthesis
Nucleic acid synthesis
By Jitendra Bhangale
Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad7
© 2010 Smt N. M. Padalia
Peptidoglycan constitutes the cell wall of bacteria
For Gram-negative organisms the bag consists of a single
thickness, but for Gram-positive organisms, it is up to
40 layers thick.
Each layer consists of multiple backbones of amino
sugars-alternating N-acetylglucosamine and
N-acetylmuramic acid residues
The latter having short peptide side-chains that are cross-
linked to form a latticework.
By Jitendra Bhangale
Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad8
© 2010 Smt N. M. Padalia
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5. 7/19/2012
The cross-linking is responsible for the
strength that allows the cell wall to resist
the high internal osmotic pressure.
The peptidoglycan is one gigantic molecule
with a molecular weight of many millions,
constituting up to 10-15% of the dry
weight of the cell.
By Jitendra Bhangale
Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad9
© 2010 Smt N. M. Padalia
First, N-acetylmuramic acid, which has attached to it both UDP
and a pentapeptide, is transferred to the C55 lipid carrier in
the membrane, with the release of UMP.
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© 2010 Delmar, Cengage Learning
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6. 7/19/2012
This is followed by a reaction with UDP-N-acetylglucosamine,
resulting in the formation of a disaccharide carrying the
pentapeptide and attached to the carrier.
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© 2010 Delmar, Cengage Learning
In Staphylococcus aureus, the five glycine residues are attached
to the peptide chain at this stage
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© 2010 Delmar, Cengage Learning
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7. 7/19/2012
The 'building block' is now transported to the outside of the cell and
added to the growing end of the peptidoglycan, the 'acceptor', with the
release of the C55 lipid, which still has two phosphates attached.
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© 2010 Delmar, Cengage Learning
The lipid then loses one phosphate group and thus becomes
available for another cycle.
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© 2010 Delmar, Cengage Learning
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8. 7/19/2012
Cycloserine is a structural analogue of D-alanine and prevents
the addition of the two terminal alanines to the initial
tripeptide side-chain on N-acetylmuramic acid.
Vancomycin inhibits the release of the building block unit from
the carrier, thus preventing its addition to the growing end
of the peptidoglycan.
Bacitracin interferes with the regeneration of the lipid carrier by
blocking its dephosphorylation.
Penicillins, cephalosporins and other β-lactams inhibit the
final transpeptidation.
By Jitendra Bhangale
15
Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad
© 2010 Smt N. M. Padalia
Protein synthesis takes place in the ribosomes.
The bacterial ribosome consists of a 50S subunit and a 30S subunit
whereas in the mammalian ribosome the subunits are 60S and 40S.
The other elements involved in peptide synthesis are messenger
RNA (mRNA), and transfer RNA (tRNA),
The ribosome has three binding sites for tRNA, the A, P and E sites.
mRNA, which is transcribed from DNA, becomes attached to the
30S subunit of the ribosome.
The 50S subunit then binds to the 30S subunit to form a 70S*
subunit, which moves along the mRNA so that successive
codons** of the messenger pass along the ribosome from the A
position to the P position
By Jitendra Bhangale
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Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad
© 2010 Smt N. M. Padalia
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9. 7/19/2012
A ribosomes (with 3 binding
sites for t RNA: the P, A, and E
sites).
A tRNA with the growing
peptide chain is in the P site,
bound by codon:anticodon
recognition. The incoming tRNA
carries valine covalently linked.
Competition with tRNA for the A
site selectively largely through
selective uptake by active
transport into prokaryotic cells
By Jitendra Bhangale
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Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad
© 2010 Smt N. M. Padalia
The incoming tRNA binds to the
A site by complementary
base pairing.
Abnormal codon:anticodon
leads to misreading of the
message.
e.g. Aminoglycosides
By Jitendra Bhangale
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Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad
© 2010 Smt N. M. Padalia
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10. 7/19/2012
Transpeptidation occurs i.e. the
peptide chain on the
tRNA in the P site is
transferred to the tRNA
on the A site.
The tRNA in the P site has been
discharged i.e. has lost its
peptides.
Premature termination of
peptide chain which
resembles the amino acid
end of tRNA.
By Jitendra Bhangale
19
Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad
© 2010 Smt N. M. Padalia
The tRNA from which the
peptide chain has been
removed is ejected.
A new tRNA, with amino acid
attached and with the
relevent anticodon, now
moves into the A site, and
the whole process is
repeated.
By Jitendra Bhangale
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Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad
© 2010 Smt N. M. Padalia
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11. 7/19/2012
By inhibiting the synthesis of the nucleotides
By altering the base-pairing properties of the
template
By inhibiting either DNA or RNA polymerase
By inhibiting DNA gyrase
By direct effects on DNA itself.
By Jitendra Bhangale
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Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad
© 2010 Smt N. M. Padalia
By Jitendra Bhangale
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Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad
© 2010 Smt N. M. Padalia
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