UNIT-1 ANTIBIOTIC.pptx UNIT 1 B.PHARM 601T

IIMT College of Pharmacy, Greater Noida
Antibiotic
Ms. Bharti Chauhan
(ASSISTANT
PROFESSOR)
Unit: I
Subject Name- Medicinal Chemistry-III
BP-601T
B Pharm VI Sem

UNIT – I
Antibiotic 08 Hours
Antibiotics Historical background, Nomenclature, Stereochemistry,
Structure activity relationship, Chemical degradation classification and
important products of the following classes.
β-Lactam antibiotics: Penicillin, Cepholosporins, β- Lactamase
inhibitors, Monobactams
Aminoglycosides: Streptomycin, Neomycin, Kanamycin Tetracyclines:
Tetracycline, Oxytetracycline, Chlortetracycline, Minocycline,
Doxycycline
SYLLABUS

• Introduction
• Introduction of antibiotics.
• Classification and mode of action β-Lactam antibiotics
• Introduction of synthetic antifungal agents
• Classification and mode of Penicillin, Cepholosporins, β- Lactamase
inhibitors, Monobactams
• Structure activity relationship of β-Lactam antibiotics
• Introduction of Aminoglycosides: Streptomycin, Neomycin,
Kanamycin Tetracyclines.
• Tetracycline, Oxytetracycline, Chlortetracycline, Minocycline,
Doxycycline
3
CONTENT

Upon completion of the course student shall be able to
1. Understand the importance of drug design and different techniques
of drug design.
2. Understand the chemistry of drugs with respect to their biological
activity.
3. Know the metabolism, adverse effects and therapeutic value of
drugs.
4. Know the importance of SAR of drugs.
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COURSE OBJECTIVE

5
COURSE OUTCOME
CO No. CO STATEMENT LEVEL OF TAXONOMY
CO1.1 History and Different types of
antibiotics.
Level I
(Remembering)
CO1.2 Mode and action and structure
activity relationship of β-Lactam
antibiotics
Level II
(Understanding)
CO1.3 Use and adverse effect of β-
Lactam antibiotics .
Level III
(Applying)
After completion of this unit it is expected that students will be able to

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PROGRAMME OUTCOMES (POs)
PO 1 Pharmacy Knowledge: Possess knowledge and comprehension of the core
and basic knowledge associated with the profession of pharmacy,
including biomedical sciences; pharmaceutical sciences; behavioral,
social, and administrative pharmacy sciences; and manufacturing
practices.
PO 2 Planning Abilities: Demonstrate effective planning abilities including time
management, resource management, delegation skills and organizational
skills. Develop and implement plans and organize work to meet deadlines
PO 3 Problem analysis: Utilize the principles of scientific enquiry, thinking
analytically, clearly and critically, while solving problems and making
decisions during daily practice. Find, analyze, evaluate and apply
information systematically and shall make defensible decisions.
PO 4 Modern tool usage: Learn, select, and apply appropriate methods and
procedures, resources, and modern pharmacy-related computing tools
with an understanding of the limitations.

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PO 5 Leadership skills: Understand and consider the human reaction to change,
motivation issues, leadership and team-building when planning changes
required for fulfillment of practice, professional and societal
responsibilities. Assume participatory roles as responsible citizens or
leadership roles when appropriate to facilitate improvement in health
and wellbeing.
PO 6 Professional Identity: Understand, analyze and communicate the value of
their professional roles in society (e.g. health care professionals, promoters
of health, educators, managers, employers, employees).
PO 7 Pharmaceutical Ethics: Honour personal values and apply ethical principles
in professional and social contexts. Demonstrate behavior that recognizes
cultural and personal variability in values, communication and lifestyles.
Use ethical frameworks; apply ethical principles while making decisions
and take responsibility for the outcomes associated with the decisions.

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PO 8 Communication: Communicate effectively with the pharmacy community
and with society at large, such as, being able to comprehend and write
effective reports, make effective presentations and documentation, and
give and receive clear instructions.
PO 9 The Pharmacist and society: Apply reasoning informed by the contextual
knowledge to assess societal, health, safety and legal issues and the
consequent responsibilities relevant to the professional pharmacy practice
PO 10 Environment and sustainability: Understand the impact of the professional
pharmacy solutions in societal and environmental contexts, and
demonstrate the knowledge of, and need for sustainable development
PO 11 Life-long learning: Recognize the need for, and have the preparation and
ability to engage in independent and life-long learning in the broadest
context of technological change. Self access and use feedback effectively
from others to identify learning needs and to satisfy these needs on an
ongoing basis.

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CO-PO MAPPING
The CO-PO mapping has been done with correlation levels of 3, 2, 1 and
‘-‘. The notation of 3, 2 and 1 denotes substantially (high), moderately
(medium) and slightly (low). The meaning of ‘-‘is no correlation between
CO and PO.
PO PO
1
PO
2
PO3 PO
4
PO
5
PO6 PO7 PO8 PO9 PO
10
PO
11
CO1.1 3 - 1 3 - - - - 1 - -
CO1.2 3 - 1 3 - - - - 1 - -
CO1.3 3 - 1 3 - - - - 1 - -

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Topic Objective mapping with CO
Name of Topic Objective of topic Mapping with
CO
Antibiotic
β-Lactam antibiotics
Aminoglycosides
Tetracycline,
Introduction, Mechanism Of Action of
Aminoglycosides
Tetracycline Antibiotic
CO1.1
Classificaion Classify the β-Lactam antibiotics
Aminoglycosides
CO1.2
Synthesis and SAR Structure activity relationship and
Synthesis of
Aminoglycosides
CO1.3
• Mapping of Course Outcomes with Topic:

• Subject covers pharmacology of various diseases and chemistry of
drugs along with SAR and their uses.
• Student must have the knowledge of pharmacology of discussed
diseases before going to chemistry of drugs used for the same.
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ANTIBIOTICS (CO-1.1)

Antibiotic:
Substances derived from a microorganism or produced synthetically,
that destroys or limits the growth of a living organism
 A drug used to treat bacterial infections.
 Antibiotics have no effect on viral infections.
 Originally, an antibiotic was a substance produced by one
microorganism that selectively inhibits the growth of another.
 Synthetic antibiotics, usually chemically related to natural antibiotics,
have since been produced that accomplish comparable tasks.
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Classification of antibiotics
• Sources
1. Natural
a. Fungi – penicillin, griseofulvin
b. Bacteria – Bacillus sp. (polymixin, bacitracin) ;
Actinomycetes (tetracycline, chloramphenicol,
streptomycin)
2. Synthetic
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ANTIBIOTICS (CO-1)

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History of Antibiotics (continue ..)
• Antibiotics have been used for millennia to treat infections, although
until the last century or so people did not know the infections were
caused by bacteria
• Various molds and plant extracts were used to treat infections by some
of the earliest civilizations – the ancient Egyptians, for example,
applied moldy bread to infected wounds
• It wasn’t until the late 19th century that scientists began to observe
antibacterial chemicals in action. Paul Ehrlich, a German physician,
noted that certain chemical dyes colored some bacterial cells but not
others. He concluded that, according to this principle, it must be
possible to create substances that can kill certain bacteria selectively
without harming other cells

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• In 1909, he discovered that a chemical called arsphenamine was an
effective treatment for syphilis.
• This became the first modern antibiotic, although Ehrlich himself
referred to his discovery as 'chemotherapy' – the use of a chemical to
treat a disease
• The word 'antibiotics' was first used over 30 years later by the
Ukrainian-American inventor and microbiologist Selman Waksman,
who in his lifetime discovered over 20 antibiotics.

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• Alexander Fleming was, it seems, a bit disorderly in his work and
accidentally discovered penicillin.
• Upon returning from a holiday in Suffolk in 1928, he noticed that a
fungus, Penicillium notatum, had contaminated a culture plate
of Staphylococcus bacteria he had accidentally left uncovered.
• The fungus had created bacteria-free zones wherever it grew on the
plate.
• Fleming isolated and grew the mold in pure culture.
• He found that P. notatum proved extremely effective even at very low
concentrations, preventing Staphylococcus growth even when diluted
800 times, and was less toxic than the disinfectants used at the time..

15
• After early trials in treating human wounds, collaborations with
British pharmaceutical companies ensured that the mass production of
penicillin (the antibiotic chemical produced by P. notatum) was
possible.
• Following a fire in Boston, Massachusetts, USA, in which nearly 500
people died, many survivors received skin grafts which are liable to
infection by Staphylococcus.
• Treatment with penicillin was hugely successful, and the US
government began supporting the mass production of the drug.
• By D-Day in 1944, penicillin was being widely used to treat troops
for infections both in the field and in hospitals throughout Europe. By
the end of World War II, penicillin was nicknamed 'the wonder drug'
and had saved many lives.

Difference between the bactericidal and bacteriostatic
 Tetracyclines
 Spectinomycin
 Sulphonamides
 Macrolides
 Chloramphenicol
 Trimethoprim
Bactericidal Antibiotics
 Penicillins
 Cephalosporins •
 Fluoroquinolones
(Ciprofloxacin) •
 Glycopeptides
(Vancomycin) •
 Monobactams
 Carbapenems
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Bacteriostatic Antibiotics

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Classifications of antibiotics

Mode action of antibiotics
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Inhibitors of DNA synthesis
Inhibitors of bacterial protein synthesis
Inhibitors of bacterial cell wall synthesis
Interference with metabolism
Impairment of nucleic acids

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ANTIBIOTICS (CO-1)
Inhibitors of DNA synthesis
Inhibitors of bacterial protein synthesis
Inhibitors of bacterial cell wall synthesis
Interference with metabolism
Impairment of nucleic acids

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β-lactam antibiotics (beta-lactam antibiotics) are antibiotics that
contain a beta-lactam ring in their molecular structure.
This includes penicillin derivatives
(penams), cephalosporins (cephems), monobactams, carbapenems and
carbacephe

Penicillin
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ANTIBIOTICS (CO-1)
Penicillin is a secondary metabolite produced by certain bacteria,
which is used an antibiotic .
A bacterial infection is caused by millions of tiny bacteria that are
trying to survive and in multiply the body . An antibiotic attacks and
kill these bacteria .
 Before the development of penicillin , many people suffered and
died from bacterial infections that are no longer considered
dangerous today

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HISTORY
1928 – ALEXANDER FLEMING Bread mold (Penicillium notatum)
growing on petri dish
1939 – FLOREY , Chain, and Associates Began work on isolating
and synthesizing large amounts of penicillin.
1941 – Introduced in antibacterial therapy
1944 – penicillin has been at the disposal of all people
History ALEXANDER FLEMING
PROPERTIES
Optically active
Soluble in water.
 Acid resistant.
Hydrolyzed by hot inorganic acid .
 Effective in treatment of respiratory track infection .

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Clasification
1.Natural penicillin's
 penicillin G
Penicillin VK
2.Beta lactase resistant penicillin's
3.Aminopenicillins penicillin G Penicillin VK Methicillin nafcillin
Ampicillin amoxicillin
4.Carboxypenicillins
5.Ureidopenicillins
6.penicillin/inihibitor combination Carcenicillin ticarcillin
Mezlocillin piperacillin Ampicillin/sulbactam Ticarcillin/clavulanate

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ANTIBIOTICS (CO-1)
PenicillinV (Phenoxymethylpenicillin)
Effective Against: • Gram positive + Less
effective against Gram negative bacteria
Treatment For: • Tonsillitis • Anthrax •
Rheumatic fever • Streptococcal skin infections
Characteristics: • Narrow spectrum • Should be
given orally • Prone to beta-lactamase
Penicillin G (Benzylpenicillin)
Narrow spectrum antibiotic.
Primarily to gram positive bacteria and few
others, active agains, Cocci-Streptococci
(except group D), Staph.aureus ; gram
negative N.gonorrheoe and

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What is the difference between penicillin G and penicillin V?
Penicillin G is a natural penicillin that is produced directly from
fermentation of Penicillium crysogenum. Penicillin V is a
derivative of penicillin G and because of similarities in spectrum
of activity, is considered a natural penicillin.
Penicillin G benzathine, potassium, procaine and sodium are
currently available in the United States in parenteral
formulations for intravenous or intramuscular use. Penicillin
V potassium (also called phenoxymethyl penicillin) is a more
acid stable and can be administered orally.

SAR OF PENICILLI

SAR OF PENICILLI
5/8/2024 Chandana majee BP-601T Med.Chem-III Unit-1 16

MECHANISM OF ACTION OF PENICILLIN
Penicillin and other antibiotics in the beta-lactam family contain a characteristic four-membered
beta-lactam ring. Penicillin kills bacteria through binding of the beta-lactam ring to DD-
transpeptidase, inhibiting its cross-linking activity and preventing new cell wall formation.
Without a cell wall, a bacterial cell is vulnerable to outside water and molecular pressures,
which causes the cell to quickly die. Since human cells do not contain a cell wall, penicillin
treatment results in bacterial cell death without affecting human cells.
Gram-positive bacteria have thick cell walls containing high levels of peptidoglycan, while gram-
negative bacteria are characterized by thinner cell walls with low levels of peptidoglycan. The
cell walls of gram-negative bacteria are surrounded by a lipopolysaccharide (LPS) layer that
prevents antibiotic entry into the cell. Therefore, penicillin is most effective against gram-
positive bacteria where DD-transpeptidase activity is highest.

Nomenclature
(a) There are two types of numbering for the fused bicycling system of
penicillin: whether which atom is number one Sulfur or Nitrogen.
(b) Penam nucleus is used in naming which comprise bicyclic system
with the amide carbonyl group. Penicillin is named as 6-acylamino-
2,2-dimethylpenam-3-carboxylic acid.
(c) Penicillanic acid nucleus: Which includes the 2,2-dimethyl and 3-
carboxyl groups. Penicillin is named as 6- carbonylaminopenicillanic
acid.
(d) Penicillin nucleus: Which includes 6-carbonyl aminopenicillanic acid.
So Penicillin G is named benzylpenicillin if R is benzene ring

Nomenclature

Stereochemistry
(a) The penicillin molecule contains three chiral carbon atoms at C-3, C-5 and
C-6
(b) All natural and synthetic penicillins have the same absolute configuration
about these three centers
(c) The 6 carbon atom bearing the acyl amino group has the L-configuration,
whereas the carbon to which the carboxyl group was attached has the D-
configuration.
(d) The acyl amino group and carboxyl group are trans to each other, with the
former and latter in the β orientation relative to penam ring.
(e) The absolute stereochemistry of the penicillins is designated as 35: 5R: 6R.
(f) The atoms composing the 6-aminopenicillanic acid are biosynthetically
derived from two amino acids, Lcysteine and D-valine

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Mechanism of action penicillinen

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β- Lactamase enzyme
Beta-lactamases are enzymes produced by bacteria that
provide multi- resistance to β-lactam antibiotics such
as penicillins, cephalosporins, cephamycins,
and carbapenems (ertapenem), although carbapenems are
relatively resistant to beta-lactamase.
In Gram-negative bacteria, β-lactamase enzymes that hydrolyze
the amide bond of the four-membered β-lactam ring are the
primary resistance mechanism,

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β- Lactamase inhibitors:
Beta-lactamases are a family of enzymes involved in
bacterial resistance to beta-lacta antibiotics. They act by breaking
the beta-lactam ring that allows penicillin-like antibiotics to work.
Beta-lactamase enzymes are produced by certain strains of the
followingbacteria: Bacteroides species, Enterococcus species, Hemo
philus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae,
and Staphylococcus species, either constitutively or on exposure to
antimicrobials.
Beta-lactamases cleave the beta-lactam ring of susceptible
penicillins and cephalosporins, inactivating the antibiotic. Some
antimicrobials (eg, cefazolin and cloxacillin) are naturally resistant
to certain beta-lactamases.

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Clavulanic acid contains a beta-lactam ring and binds strongly to
beta-lactamase at or near its active site, thereby hindering
enzymatic activity. This protects other beta-lactam antibiotics from
beta-lactamase catalysis, thereby enhancing their antibacterial
effects.

Chandana majee BP-601T Med.Chem-III Unit-1 16
5/8/2024
Clavulanic acid contains a beta-lactam ring and binds strongly to
beta-lactamase at or near its active site, thereby hindering
enzymatic activity. This protects other beta-lactam antibiotics from
beta-lactamase catalysis, thereby enhancing their antibacterial
effects.

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Clavulanic acid
Clavulanic Acid is a semisynthetic beta-
lactamase inhibitor isolated from
Streptomyces. Clavulanic acid contains a
beta-lactam ring and binds strongly to beta-
lactamase at or near its active site, thereby
hindering enzymatic activit :
.

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Clavulanic acid
Clavulanic Acid is a semisynthetic beta-
lactamase inhibitor isolated from
Streptomyces. Clavulanic acid contains a
beta-lactam ring and inds strongly to beta-
lactamase at or near its active site, thereby
hindering enzymatic activit :
.

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Clavulanic acid
The combination of amoxicillin
and clavulanic acid is used to treat certain
infections caused by bacteria, including
infections of the ears, lungs, sinus, skin, and
urinary tract. Amoxicillin is in a class of
medications called penicillin-like antibiotics. It
works by stopping the growth of bacteria.
.

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β- Lactamase inhibitors
Bactericidal Act by acylation
Clavulanic acid,
sulbactam,
and tazobactam
Avibactam,
vaborbactam,
and relebactam

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β-LACTAM ANTIBIOTICS
(PENICILLI) (CO-1.1)

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β-LACTAM ANTIBIOTICS (CO-1.1)
• The cephalosporins were isolated from the fungus Cephalosporium
acremonium in 1948 by Pro Tzu, Newton, and Abraham (1953)
• Cephalosporins contain dihydrothiazine ring, while penicillin contains
a tetrahydrothiazole (thiazolidine) ring
• The cephalosporins are much more acid stable than the corresponding
penicillins.
• Cephalosporins can be divided into three classes:
1. Cephalosporin N: penicillin-like structure - a derivative of 6-
aminopenicillanic acid.
2. Cephalosporin P: An acidic antibiotic, which is steroidal in nature
3. Cephalosporin-C: It is a true cephalosporin and it is a derivative of 7
amino-cephalosporanic acid – semi synthetic derivatives
Cephalosporins

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Cephalosporins
• Cepham is the name given to the unsubstituted
bicyclic lactam.

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Classification Cephalosporins
(Route of administration)
a. Orally administered: cephalexin, cephradine, and cefaclor
b. Parentrally administered: cephalothin, cephapirin, cephacetrile, and
cefazedone. These agents are sensitive to β-lactamase
c. Resistant to β-lactamase and parentrally administered: cefuroxime,
cefamandole, cefoxitin
d. Metabolically unstable: cephalothin and cephapirin

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• First generation cephalosporins - Cephalexin, cephadroxil,
cephradine and cephalothine
• Second-generation cephalosporins - Cefaclor, cefamandole
• Third-generation cephalosporins – Cefotaxime, ceftizoxime
• Fourth generation – Cefepime, Cefpirome

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Degradation of cephalosporins
In prescence of strong acids - inactive lactone

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SAR of cephalosporins
1. 7-Acylamino substituents:
(i) Acylation of amino group generally increases the potency against gram-
positive bacteria, but decreases gram-negative potency.
(ii) Substituents on the aromatic ring that increases lipophilicity provide higher
gram- positive activity and generally lower gram-negative activity.
(iii) The phenyl ring in the side-chain can be replaced with other heterocycles
with improved spectrum of activity and pharmacokinetic properties, and
these include thiophene, tetrazole, furan, pyridine

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• 2. C-3 substituents:
• influences pharmacokinetic and pharmacological properties as well as
antibacterial activity. Modification at C-3 position has been made to reduce the
degradation of cephalosporins.
(i) The benzoyl ester - improved gram-positive activity but lower gram-negative
activity.
(ii) Pyridine and imidazole- show improved activity against P. aeruginosa.
• azide ion with relatively low gram-negative activity.
(iii) aromatic thiols of 3-acetoxy group results in an enhancement of activity against
gram-negative bacteria with improved pharmacokinetic properties.
(iv) Replacement of acetoxy group at C-3 position with —CH3, Cl has resulted in
orally active compounds.

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3. Introduction of C-7 α-methoxy group shows higher resistance to hydrolysis by
β-lactamases
4. Oxidation of ring sulphur to sulphoxide or sulphone greatly diminishes or
destroys the antibacterial activity.
5. Replacement of sulphur with oxygen leads to oxacepam with increased
antibacterial activity, with methylene group - greater chemical stability and a
longer half-life.
6. The carboxyl group of position-4 has been converted into ester prodrugs to
increase bioavailability of cephalosporins, and these can be given orally as well.
Examples include cefuroxime axetil and cefodoxime proxetil.
7. Olefinic linkage at C 3-4 is essential for antibacterial activity. Isomerization of
the double bond to 2-3 position leads to great losses in antibacterial activity

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Nomenclature of cephalosporins
a) The chemical nomenclature of the cephalosporins is slightly more
complex than even that of the penicillins because of the presence
of a double bond in the dihydrothiazine ring.
b) The fused ring system is designated by Chemical Abstracts as 5-
thia-1-azabicyclo[4.2.0]oct-2-ene.
c) In this system, cephalothin is 3-(acetoxymethyl)-7-[2-
(thienylacetyl)amino]-8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-ene-
2-carboxylic acid.

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Monobactams
Monobactams are monocyclic and bacterially-produced β-lactam
antibiotics. The β-lactam ring is not fused to another ring, in
contrast to most other β-lactams. Monobactams are effective only
against aerobic Gram-negative bacteria (e.g., Neisseria,
Pseudomonas)

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Monobactams
They are resistant to β-lactamases and active against aerobic gram-
negative rods.
They have no activity against gram-positive bacteria or anaerobes.
Aztreonam is the only commercially available monobactam.
It is administered either IV or IM and can accumulate in patients with
renal failure.
Relatively nontoxic, but it may cause phlebitis, skin rash, and,
occasionally, abnormal liver function tests.
Penicillin-allergic patients tolerate aztreonam without reaction.
Monobactams have monocyclic beta lactam ring and are resistant to
beta lactamse

Aminoglycosides
Aminoglycosides are a class of antibiotics used to treat serious
infections caused by bacteria that either multiply very quickly
or are difficult to treat. Aminoglycosides are called
bactericidal antibiotics because they kill bacteria directly.
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Aminoglycosides
Aminoglycosides display concentration-dependent bactericidal
activity against "most gram-negative aerobic and facultative
anaerobic bacilli" but not against gram-negative anaerobes and
most gram-positive bacteria. They require only short contact
time and are most effective against susceptible bacterial
populations that are rapidly multiplying.
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NH2
N
H2

SAR OF AMINIGLYCOSIDE
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ANTIBIOTICS (CO-1)

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ANTIBIOTICS (CO-1)
6 amino group
increses the activity
6 amino group replace by OH
decreases the activity
2 amino group
increses the activity
1
2
Acetylating retain the activity

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1
2

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AMINOGYCOSIDE
AMINO + GYCOSIDE Polybasic amino groups linked
glycosidically to two or more aminosugar.

Amino Glycoside MOA
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Amino Glycoside MOA
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Aminogycoside are polar so they can not penetrate the peptidoglycan layer
Amino glycoside
Amino glycoside

Aminogycoside are polar so they can not penetrate the peptidoglycan layer
Amino glycoside
Amino glycoside

Streptomycin
Streptomycin is an antibiotic medication used to treat a
number of bacterial infections
Streptomycin was discovered in 1943 by Albert Schatz
from Streptomyces griseus. It is on the World Health
Organization's List of Essential Medicines.
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Streptomycin
5/8/2024
Chandana majee BP-601T
Med.Chem-III Unit-1
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O
O
OH
OH
N
NH
H2N
HO
N
H2N
NH2
O
O OH
OH
OH
HN
O
OH
N Methyl –L-
glucosamine
L -sterptose
Streptidine

Streptomycin
• Streptomycin, like other aminoglycosidic antibiotics (e.g.,
gentamycin, neomycin, kanamycin, tobramycin), inhibits
protein synthesis in bacterial cells by binding to the 30S
subunit of ribosomes.
• By doing so, the streptomycin causes a structural change
which interferes with the recognition site of codon-anticodon
interaction resulting in misreading of the genetic message
carried by messenger RNA (mRNA). The mechanism of
inhibition of protein synthesis by streptomycin is
schematically shown in
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Streptomycin MOA
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Streptomycin
 Infective endocarditis caused by enterococcus when the
organism is not sensitive to gentamicin
 Tuberculosis in combination with other antibiotics. For active
tuberculosis it is often given together with isoniazid,
rifampicin, and pyrazinamide.
 It may be useful in cases where resistance to other drugs is
identified.
 Plague (Yersinia pestis) has historically been treated with it as
the first-line treatment. However streptomycin is approved for
this purpose only by the U.S. Food and Drug Administration. •
 In veterinary medicine, streptomycin is the first-line antibiotic
for use against gram negative bacteria in large animals (horses,
cattle, sheep, etc.). It is commonly combined with procaine
penicillin for intramuscular injection. • Tularemia infections
have been treated mostly with streptomycin.
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Neomycine
Neomycin was discovered in 1949 by the
microbiologist Selman Waksman and his student Hubert
Lechevalier at Rutgers University. It is produced naturally by
the bacterium Streptomyces fradiae
Neomycin is an aminoglycoside antibiotic that displays
bactericidal activity against gram-negative aerobic bacilli and
some anaerobic bacilli where resistance has not yet arisen. It is
generally not effective against gram-positive bacilli and
anaerobic gram-negative bacilli. Neomycin comes in oral and
topical formulations, including creams, ointments, and
eyedrops. Neomycin belongs to the aminoglycosid class of
antibiotics that contain two or more amino sugars connected
by glycosidic bonds
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ANTIBIOTICS (CO-1)

Neomycine
Similar to other aminoglycosides, neomycin has excellent
activity against gram-negative bacteria and is partially
effective against gram-positive bacteria. It is relatively toxic to
humans, with allergic reactions noted as a common adverse
reaction (see: hypersensitivity). Physicians sometimes
recommend using antibiotic ointments without neomycin, such
as Polysporin. The following represents minimum inhibitor
concentration (MIC) susceptibility data for a few medically
significant gram-negative bacteria.s
• Enterobacter cloacae: >16 μg/ml
• Escherichia coli: 1 μg/ml
• Proteus vulgaris: 0.25 μg/ml
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Neomycine
In 2005–06, Neomycin was the fifth-most-prevalent allergen
in patch test results (10.0%). It is also a known
GABA gamma-Aminobutyric acid antagonist and can be
responsible for seizures and psychosis. Like other
aminoglycosides, neomycin has been shown to be ototoxic,
causing tinnitus, hearing loss, and vestibular problems in a
small number of patients. Patients with existing tinnitus or
sensorineural hearing loss are advised to speak with a
healthcare practitioner about the risks and side effects prior to
taking this medicatio
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Neomycine
Neomycin is typically applied as a topical preparation, such as
Neosporin (neomycin/polymyxin B/bacitraci). The antibiotic
can also be administered orally, in which case it is usually
combined with other antibiotics. Neomycin is not absorbed
from the gastrointestinal tract and has been used as a
preventive measure for hepatic
encephalopath and hypercholesterolemi. By killing bacteria in
the intestinal tract, Neomycin keeps ammonia levels low and
prevents hepatic encephalopathy, especially
before gastrointestinal surgery.
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ANTIBIOTICS (CO-1)

Kanamycin
• Kanamycin A, often referred to simply as kanamycin, is
an antibiotic used to treat severe bacterial
infections and tuberculosis. It is not a first line treatment. It is
used by mouth, injection into a vein, or injection into a
muscle. Kanamycin is recommended for short-term use only,
usually from 7 to 10 days. As with most antibiotics, it is
ineffective in viral infections.
• Common side effects include hearing and balance
problems. Kidney problems may also occur. Kanamycin is not
recommended during pregnancy as it may harm the baby. It is
likely safe during breastfeeding. Kanamycin is in
the aminoglycoside family of medications. It works by
blocking the production of proteins that are required for
bacterial survival
16
ANTIBIOTICS (CO-1)

Kanamycin
• Spectrum of activity
• Kanamycin is indicated for short-term treatment of bacterial
infections caused by one or more of the following
pathogens: E. coli, Proteus species (both indole-positive and
indole-negative), Enterobacter aerogene, Klebsiella
pneumoniae, Serratia marcescens, and Acinetobacter species.
In cases of serious infection when the causative organism is
unknown, Kanamycin injection in conjunction with
a penicillin- or cephalosporin-type drug may be given initially
before obtaining results of susceptibility testing.
• Kanamycin does not treat viral infections
16

Tetracyclines
Tetracyclines are a group of broad-
spectrum antibiotic compounds that have a common basic
structure and are either isolated directly from several species
of Streptomycesbacteria or produced semi-synthetically from
those isolated compounds.Tetracycline molecules comprise a
linear fused tetracyclic nucleus (rings designated A, B, C and
D) to which a variety of functional groups are
attached.Tetracyclines are named for their four ("tetra-")
hydrocarbon rings ("-cycl-") derivation ("-ine"). They are
defined as a subclass of polyketides, having an
octahydrotetracene-2-carboxamide skeleton and are known
as derivatives of polycyclic naphthacene carboxamide.While
all tetracyclines have a common structure, they differ from
each other by the presence of chloride, methyl,
and hydroxyl groups.
16

Tetracycline
Tetracyclines are growth inhibitors (bacteriostatic) rather
than killers of the infectious agent (bacteriocidal) and are
only effective against multiplying microorganisms. They
are short-acting and passively diffuse through porin
channels in the bacterial membrane. They inhibit protein
synthesis by binding reversibly to the bacterial 30S
ribosomal subunit and preventing the aminoacy
tRNA from binding to the A site of the ribosome. They
also bind to some extent the bacterial 50S ribosomal
subunit and may alter the cytoplasmic
membrane causing intracellular components to leak from
bacterial cells.
16

TETRACYCLINE MODE OF ACTION
Tetracycline antibiotics are protein synthesis
inhibitors. They inhibit the initiation of translation in
variety of ways by binding to the 30S ribosomal subunit,
which is made up of 16S rRNA and 21 proteins. They
inhibit the binding of aminoacyl-tRNA to the mRNA
translation complex. Some studies have shown that
tetracyclines may bind to both 16S and 23S
rRNAs.Tetracyclines also have been found to
inhibit matrix metalloproteinases. This mechanism does
not add to their antibiotic effects, but has led to extensive
research on chemically modified tetracyclines or CMTs
(like incyclinide) for the treatment
of rosacea, acne, diabetes and various types of neoplasms.

OXYTERTACYCLINE
Oxytetracycline is a tetracycline used for treatment of
infections caused by a variety of Gram positive and
Gram negative microorganisms including
Mycoplasma pneumoniae, Pasteurella pestis,
Escherichia coli, Haemophilus influenzae (respiratory
infections), and Diplococcus pneumoniae.

OXYTERTACYCLINE USES
Oxytetracycline, like other tetracyclines, is used to treat
many infections, both common and rare (see Tetracycline
antibiotics group). Its better absorption profile makes it
preferable to tetracycline for moderately severe acne at a
dosage of 250–500 mg four times a day for usually six to
eight weeks at a time, but alternatives should be sought if
no improvement occurs by three months.
Oxytetracycline is used to treat infections of the respiratory and
urinary tracts, skin, ear, eye and gonorrhoea although its use for such
purposes has declined in recent years due to large increases in
bacterial resistance to this class of drugs. The drug is particularly
useful when penicillins and/or macrolides cannot be used due to
allergy.

OXYTERTACYCLINE SIDE EFFECTS
Side effects are mainly gastrointestinal and photosensitive
allergic reactions common to the tetracycline antibiotic group.
It can also damage calcium-rich organs, such as teeth and
bones, although this is very rare. It sometimes causes nasal
cavities to erode; quite commonly, the BNF suggests, because
of this, tetracyclines should not be used to treat pregnant or
lactating women and children under 12 except in certain
conditions where it has been approved by a specialist because
there are no obvious substitutes. Candidiasis (thrush) is not
uncommon following treatment with broad-spectrum
antibiotics.
16

Question-5: Aminoglycosides are commonly administered with
penicillins in chronic infections i) true ii) false
Question-6Clavulanic acid is example of i) beta lactam antibiotics ii)
aminoglycoside iii) macroliodesiv) beta lactamase inhibitor
Question-7 Third and fourth generation cephalosporins have greater
gram negative activity than first generation cephalosporins i) true ii)
false
174
Daily Quiz

• What are antibiotics, Discuss them in detail?
• What are beta lactam antibiotics.
• What is the difference in the basic structure of penicillins and
cephalosporins .
• What is MOA of tetracyclines.
• Discuss the uses of doxycycline
175
Weekly Assignment

Question-1 :salbactum acid is example of
i) beta lactam antibiotics
ii) ii) aminoglycoside
iii) iii) macroliodes
iv) beta lactamase inhibitor
Question-2: Cephalosporins in structure contains
i) Thaimine
ii)glycose sugar
iii) beta lactam ring
iv) thiazolidine ring
176
MCQ s

Question-3: Which of the above statement is true for cephalosporins
i) they are beta lactam antibiotics
ii) they are divided in different generations
iii) both of the above
iv) none of the above
Question-4 Neomycin is example of
i) macrolides
ii) ii) sulphonamides
iii) iii)biguanides
iv) iv) aminoglycosides False
MCQ s

• Discuss the structure activity relationship (SAR) of
Penicillins.
• Write the mechanism of action of beta lactam antibiotics
• Give classification of cephalosporins with examples.
• Discuss the mechanism of action and uses of cephalosporins.
• Define and classify aminoglycosides
178
Expected Questions for University
Exam

179
References and Books to be followed
Wilson and Giswold’s Organic medicinal and Pharmaceutical
Chemistry.
Foye’s Principles of Medicinal Chemistry.
Burger’s Medicinal Chemistry, Vol I to IV.
MEDICINAL CHEMISTRY-3 ( RNPD)
• https://www.google.com/
• https://en.wikipedia.org/wiki/Antibiotic
• https://longitudeprize.org/blog-post/overview-antibiotics
• https://www.drugs.com/drug-class/macrolides.html

UNIT-1 ANTIBIOTIC.pptx UNIT 1 B.PHARM 601T

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