*St. Augustine Campus*
Faculty of Medical Sciences
School of Pharmacy
Course: MICROBIOLOGY, IMMUNOLOGY AND GENERAL
PATHOLOGY (PHAR 2401)
07/10/2019
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Prepared By: Dr. Rajiv Dahiya
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CEPHALOSPORINS
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-lactamase resistant/sensitive
structural features
*Movement of one of the methoxy group to para position or replacement with
hydrogen results in b-lactamase sensitive agents.
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GLYCOPEPTIDES
Glycopeptides
are
peptides
that
contain carbohydrate moieties (glycans)
covalently attached to the side chains of
the amino acid residues that constitute
the peptide.
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GLYCOPEPTIDE LINKAGES
N-Linked Glycans are the glycans where
glycan is attached to an asparagine (Asn)
residue, and are amongst the most
common linkages found in nature.
GlcNAc-β-Asn
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GLYCOPEPTIDE LINKAGES
O-Linked Glycans are the glycans that
are formed by a linkage between an
amino acid hydroxyl side chain (usually
from serine or threonine) with the glycan.
GlcNac-β-Ser
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GLYCOPEPTIDE LINKAGES
C-Linked Glycans refers to the covalent
attachement of mannose to a tryptophan
residue. An example of a C-linked glycan
is α-mannosyl tryptophan. Of the three
linkages, these are least common one.
α-mannosyl tryptophan
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GLYCOPEPTIDE ANTIBIOTICS
Glycopeptide antibiotics are a class
of drugs of microbial origin that are composed
of glycosylated cyclic/polycyclic nonribosomal
peptides.
Types:Anti-infective antibiotics
e.g. Vancomycin, Teicoplanin, Telavancin,
Ramoplanin, Decaplanin
Anti-tumor antibiotics
e.g. Bleomycin
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STRUCTURES OF
GLYCOPEPTIDE ANTIBIOTICS
Vancomycin
*Vancomycin is indicated for the treatment of serious, life-threatening
infections by gram-positive bacteria unresponsive to other antibiotics.
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STRUCTURES OF
GLYCOPEPTIDE ANTIBIOTICS
*All teicoplanins share a same glycopeptide core, termed teicoplanin
A3-1 - a fused ring structure to which two carbohydrates (mannose and
N-acetylglucosamine) are attached.
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STRUCTURES OF
GLYCOPEPTIDE ANTIBIOTICS
Telavancin
(semi-synthetic derivative
of vancomycin)
*Telavancin inhibits bacterial cell wall synthesis by binding to the D-AlaD-Ala terminus of the peptidoglycan in the growing cell wall.
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STRUCTURES OF
GLYCOPEPTIDE ANTIBIOTICS
Ramoplanin
(having 49 membered
macrocyclic
depsipeptide ring with
17 amino acids)
*Telavancin is a potent inhibitor of bacterial cell wall synthesis.
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STRUCTURES OF
GLYCOPEPTIDE ANTIBIOTICS
Decaplanin
*Decaplanin was two- to four-fold less active than vancomycin, telcoplanin and
daptomycin against Staphylococcus aureus and Staphylococcus epidermidis.
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STRUCTURES OF
GLYCOPEPTIDE ANTIBIOTICS
Bleomycin
(a hybrid peptidepolyketide natural
product)
*It is recommended in Hodgkin's disease, non-Hodgkin's disease, testicular
cancer, ovarian cancer, and cervical cancer..
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AMINOGLYCOSIDE ANTIBIOTICS
Aminoglycosides are gram-negative
antibacterial therapeutic agents that
inhibit protein synthesis and contain an
amino-modified glycoside (sugar).
2-deoxystreptamine
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TYPES OF
AMINOGLYCOSIDES
Non-deoxystreptamine aminoglycosides
e.g. Streptomycin
Those having 4,6-disubstituted
deoxystreptamine
e.g Kanamycin A, Tobramycin, Amikacin
Those having 4,5-disubstituted
deoxystreptamine
e.g. Neomycins
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STRUCTURES OF
AMINOGLYCOSIDE ANTIBIOTICS
Streptomycin
*Streptomycin is produced by fermentation of Streptomyces griseus.
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STRUCTURES OF
AMINOGLYCOSIDE ANTIBIOTICS
Kanamycin A
Amikacin
*Kanamycin is isolated from Streptomyces kanamyceticus.
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STRUCTURES OF
AMINOGLYCOSIDE ANTIBIOTICS
Tobramycin
Gentamicin
*Tobramycin is produced by fermentation of Streptomyces tenebrarius
and Gentamicin is produced by fermentation of Micromonospora
purpurea.
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STRUCTURES OF
AMINOGLYCOSIDE ANTIBIOTICS
Sisomicin
Netilmicin
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STRUCTURES OF
AMINOGLYCOSIDE ANTIBIOTICS
Neomycins B, C
*Neomycins are produced by fermentation of Streptomyces fradiae.
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STRUCTURES OF
AMINOGLYCOSIDE ANTIBIOTICS
Neomycin E
(Paromomycin)
*Paromomycin is isolated from Streptomyces krestomuceticus.
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TETRACYCLINES
Tetracyclines are a group of broadspectrum antibiotics which are derivatives
of polycyclic naphthacene carboxamide
having four adjacent rings and used in the
treatment of infections of the urinary and
respiratory tract.
Basic tetracycline structure
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CLASSIFICATION OF TETRACYCLINES
According to source…
 Naturally occurring tetracyclines
e.g. Tetracycline, Chlortetracycline,
Oxytetracycline, Demeclocycline
 Semi-synthetic tetracyclines
e.g. Lymecycline, Meclocycline, Methacycline,
Minocycline, Rolitetracycline
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CLASSIFICATION OF TETRACYCLINES
According to duration of action…
 Short-acting tetracyclines
(Half life: 6-8 hrs)
e.g. Tetracycline, Chlortetracycline,
Oxytetracycline
 Intermediate-acting tetracyclines
(Half life: ~12 hrs)
e.g. Demeclocycline, Methacycline
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CLASSIFICATION OF TETRACYCLINES
According to duration of action (contd.)
 Long-acting tetracyclines
(Half life: 16 hrs & more)
e.g. Doxycycline, Minocycline,
Tigecycline
*Tetracycline antibiotics are protein synthesis inhibitors,
inhibiting the binding of aminoacyl-tRNA to the mRNAribosome complex. They do so mainly by binding to
the 30S ribosomal subunit in mRNA translation complex
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STRUCTURES OF TETRACYCLINES
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STRUCTURES OF TETRACYCLINES
Lymecyline
Tigecyline
Meclocyline
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TETRACYCLINE - PRODRUGS
Rolitetracycline
(a pyrrolidinylmethyl tetracycline)
*Rolitetracycline is a N-Mannich base prodrug which is
more hydrophilic than tetracycline and has sufficient water
solubility to allow intravenous administration
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REFERENCES
 Block JH, Beale JM, Gisvold O. Wilson and Gisvold’s
Textbook of Organic, Medicinal and Pharmaceutical
Chemistry, 11th edition, Lipincott Williams and Wilkins, 2004.
 Lemke TL, Williams DA, Roche VF, Zito WS. Foye’s Principles
of Medicinal Chemistry, 6th edition, Lipincott Williams and
Wilkins, 2008.
 Abraham DJ. Burger’s Medicinal Chemistry and Drug
Discovery, 6th edition, Wiley Interscience, 2006.
 Ashutosh Kar. Medicinal Chemistry, 4th edition, New Age
International Publishers, 2007.
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