Antibiotics

Antibiotics in medicinal chemistry

1. NEELIMA YADAV
ASSITANT PROFESSOR
DR C.V. RAMAN INSTITUTE OF PHARMACY

2. Definitions:
ANTIBIOTICS: Greek words anti (against) and biotikos
(concerning life) refers to substances produced by microorganisms,
which selectively suppress the growth of or kill other
microorganisms at very low concentration.
OR
“Antibiotics are defined as chemical substances or compounds
produced by various species of microorganisms such as bacteria and
fungi, which in low concentrations destroy, kill or inhibit the growth
of microorganisms.”
OR
“Substances produced by microorganisms, selectively suppress the
growth, kill other microorganisms at very low concentrations.”

3. CLASSIFICATION OF ANTIBIOTICS:
A.CHEMICAL STRUCTURE:,
1.Sulfonamidesand related drugs:
Sulfadiazine

4. Sulfones–(Dapsone(DDS), Paraaminosalicylicacid (PAS)
2. Diaminopyrimidines:
Trimethoprim
Pyrimethamine
3. Quinolones:
Nalidixicacid
Norfloxacin
Ciprofloxacin, etc.
4. β-lactamantibiotics:
Penicillins
Cephalosporins
5. Tetracyclines:
Oxytetracycline
Doxycycline, etc.

5. 6.Nitrobenzene derivative:
Chloramphenicol
7. Aminoglycosides:
Streptomycin
Gentamicin
Neomycin, etc.
8. Macrolideantibiotics:
Erythromycin
Clarithromycin
Azithromycin, etc.
9.Lincosamideantibiotics:
Lincomycin
Clindamycin
10. Polypeptide antibiotics:
Polymyxin-B
Bacitracin

6. 11. Glycopeptides:
Vancomycin
12.Oxazolidinone:
Linezolid
13.Nitrofuranderivatives:
Nitrofurantoin
14. Nitroimidazoles:
Metronidazole
Tinidazole
15. Nicotinic acid derivatives:
Isoniazid

7. Pyrazinamide
16. Polyeneantibiotics:
Nystatin
Amphotericin-B.
17. Azolederivatives:
Miconazole
Clotrimazole
Ketoconazole
Fluconazole
18. Others:
Rifampin
Viomycin
Ethambutol
Thiacetazone
Griseofulvin

8. B.MECHANISM OF ACTION OF ANTIMICROBIAL AGENTS :
1. Inhibition of cell wall synthesis:
Penicillins
Cephalosporins
Bacitracin
Vancomycin
2. Inhibition of functions of the cellular membrane:
Polypeptides—
Polymyxins
Bacitracin
Polyenes—
AmphotericinB
Nystatin
3. Inhibition of protein synthesis:
Chloramphenicol
Macrolides
Erythromycin
Clindamycin
Tetracyclines
Aminoglycosides
4. Inhibition of nucleic acid synthesis:
Quinolones
Rifampin

9. 5. Inhibition of folic acid synthesis:
Sulfonamides
Trimethoprim
Sulfones
Pyrimethamine
Ethambutol
6.Cause misreading of m-RNA code and affect permeability:
Aminoglycosides—
Streptomycin
Gentamicin
7. Inhibit DNA gyrase:
Fluoroquinolones—
Ciprofloxacin
8. Interfere with DNA function:
Rifampicin
Metronidazole
9. Interfere with DNA synthesis:
Acyclovir
Zidovudine

10. CLASSIFICATION OF ANTIBIOTICS
1. ON THE BASIS OF MECHANISM OF ACTION:

11. 3. ON THE BASIS OF MODE OF ACTION:
A. BACTERIOSTATIC ANTIBIOTICS:
These are effective in abolishing or preventing the growth of
bacterial species. (Stop the bacteria from growing):
Tetracycline
Chloramphenicol
Erythromycin
Lincomycin
B. BACTERIOCIDAL ANTIBIOTICS:
These are more effective in killing harmful microorganisms
particularly bacterial species (Kill the bacteria directly)
Examples are-
Cephalosporin
Penicillin
Erythromycin
Aminoglycosides
Cotrimoxazole

12. D.TYPE OF ORGANISMS AGAINST WHICH PRIMARILY ACTIVE
1. Antibacterial:
Penicillins
Aminoglycosides
Erythromycin
2.Antifungal:
Griseofulvin
AmphotericinB
Ketoconazole
3. Antiviral:
Acyclovir
Amantadine
Zidovudine
4.Antiprotozoal:
Chloroquine
Pyrimethamine
Metronidazole
5. Antihelmintic:
Mebendazole
Niclosamide
Diethyl carbamazepine

13. 1.BENZYL PENICILLIN
Structure

14. CHEMICAL NAME:
6-(2-phenyl ethanoylamino), 2,2-dimethyl, penam-3-carboxylic
acid.
OR
6-(2-phenyl acetamido), 2, 2-dimethyl penam-3-carboxylic acid.
OR
6-(2-phenyl acetamido) penicillanicacid.
PROPERTIES
PHYSICAL PROPERTIES:
Colour–white, finely crystalline powders
Odour-faint characteristic
Salt –sodium and potassium salt
Nature –hygroscopic
Solubility:
Very soluble in water

15. CHEMICAL PROPERTIES:
In strong acidic medium, penicillin undergoes degradation, in
which both β-lactumand thiazolidinerings are opened, giving
penicillanicacid.
In presence of alkali, it is hydrolysedto penicilloicacid by
opening β-lactumring.
STABILITY AND STORAGE:
The stability of benzyl penicillin depends upon moisture
content. If the moisture content is less than 0.5%, then at
room temperature, benzyl penicillin is stable for 2-3 years.
That’s why, it is stored in tight closed containers, protected
from moisture.
CATEGORY:
Antibacterial

16. USES:
Benzyl penicillin is a drug of choice to treat infections caused
by gram-positive bacteria which do not produce the enzyme
Penicillinase.
It also used to treat:
Abscesses
Syphilis
Gonorrhoea
Pharyngitis, Pneumonia, Meningitidis, endocarditisdue to
staphylococci
Scarlet fever, pneumonia, endocarditisdue to streptococci
Meningitis
Pneumococcal infections
Otitismedia
Tetanus

17. It is also used prophylactically, before dental and surgical procedures
to prevent-
Developing endocarditis
Re-occurrence of rheumatic fever
The disadvantages are that in some individuals it produces allergic
reactions and anaphylactic shock
PHARMACEUTICAL FORMULATIONS:
Benzyl penicillin injection
Benzyl penicillin eye drops
Benzyl penicillin eye ointments
Procaine penicillin injection
Fortified procaine penicillin injection
BRAND NAMES
Cyrstapen
Pentids
PAM

18. 2.BENZATHINE PENICILLIN OR BENZATHINE PENICILLIN G OR
BENZATHINE BENZYL PENICILLIN
It is N, N’-dibenzylethylene diaminesalt of benzyl penicillin. It is
practically insoluble in water and is quite stable at pH of gastric
juice.
When it is taken orally, it is hydrolysedin gut, releasing two
molecules of penicillin and is absorbed through the intestine. Due
to its low water solubility and slow release of the drug, it has a
longer duration of action.
PROPERTIES
PHYSICAL PROPERTIES
Colour–white crystalline powder
Odour–odourless
Nature –hygroscopic
Solubility –
Slightly soluble in water

19. STABILITY AND STORAGE
At room temperature and in a dry state, it retains potency
for about 5 years, when protected from moisture.
It is also affected by light, hence, it is stored in tightly
closed light-resistant containers at a temperature not
exceeding 25
0
C.
PHARMACEUTICAL FORMULATION
Tablets
Oral suspensions
Sterile suspensions
Fortified injection
BRAND NAMES
Penidure
Longacillin

20. 3.AMPICILLIN
Structure

21. CHEMICAL NAME
6-(2-amino, 2-phenyl acetamido) penicillanicacid
PROPERTIES
PHYSICAL PROPERTIES
Colour–white crystalline powder
Odour–odourless
Taste –bitter
Solubility –
Sparingly soluble in water
Very slightly soluble in alcohol
Its sodium salt is freely soluble in water
Ampicillintrihydrateis sparingly soluble in water

22. STABILITY AND STORAGE
It is unstable above 25
0
C and it is stored in a tightly closed
container, in a cool place or at a temperature not exceeding 25
0
C.
USES
It is used to treat the following infections due to susceptible
bacteria
Respiratory tract infection
Urinary tract infections
Gonorrhea
Meningitis
Enteric infections
Septicaemia
PHARMACEUTICAL FORMULATION
Capsules
Tablets
Oral suspensions
Sterile solution
Sterile injection
BRAND NAMES
Roscillin
Ampillin
Ampipen

23. 4.CARBENICILLIN
PROPERTIES
PHYSICAL PROPERTIES
Colour–white
Odour–odourless
Taste –bitter
Nature –hygroscopic
Solubility –
Freely soluble in water
Practically insoluble in ether
Practically insoluble in chloroform

24. STABILITY AND STORAGE
In presence of moisture and at room temperature, the
decarboxylationoccurs to give benzyl penicillin. Hence, it is
stored in tightly-closed light-resistant containers at a
temperature not exceeding 5
0
C.
USES
It is an antibacterial agent but orally it is poorly absorbed.
It is used in the treatment of respiratory tract infections
It is used in the treatment of urinary tract in fection(UTI)
It also used in the treatment of septicaemia
PHARMACEUTICAL FORMULATION
In the form of injection
BRAND NAMES
Carbapen
Carbelin

25. 5.CLOXACILLIN
It is a semisyntheticpenicillin and contains substituted isoxazol-
4-yl heterocycleswhich is bulker.
PROPERTIES
PHYSICAL PROPERTIES
Colour–white crystalline
Odour–odourless
Taste –bitter
Nature –hygroscopic powder
Solubility –
Freely soluble in water
Very slightly soluble in chloroform
STABILITY AND STORAGE
It is unstable above 25
0
C and is affected by moisture. Hence, it
is stored in tightly closed containers in a cool place or at a
temperature not exceeding 25
0
C.

26. USES
It is an antibacterial agent and used in the treatment
ofstaphylococcal infectionswhich are resistant to benzyl
penicillin.
It also used in the treatment of following infections due to
susceptible organism:
Respiratory tract infection
Urinary tract infections
Otitismedia
Speticaemia
Endocarditis
Meningitis
Bone and joint infections
PHARMACEUTICAL FORMULATIONS
it is available in the form of –
Tablets
Capsules
Injections
Suspensions

27. BRAND NAME
Cloxa-A
Cloxin
6.GENTAMICIN
1. It is an aminoglycosideantibiotic
2. It is a mixture of-
GentamicinC1
GentamicinC2
GentamicinC1a
3. Some samples may contain-
GentamicinC2A
GentamicinC2B
4. It is produced by micromonosporapurpureaand hence the
name ends with micin.

28. PROPERTIES
PHYSICAL PROPERTIES
Colour–white to cream colouredpowder
Odour–odourless
Taste –bitter/tasteless
Solubility –
It is soluble in water
Practically insoluble in chloroform
STABILITY AND STORAGE
Stored in tight-closed containers and in a cool place
USES
1. it is a broad-spectrum antibiotic, so it is used to treat
Septicaemiaincluding neonatal sepsis
Severe systemic infections due to sensitivegram-positive and
gram-negative bacteria.
2. It is also used for prophylaxis and treatment of endocarditis
3. It also used for prophylaxis of surgical infection

29. PHARMACEUTICAL FORMULATIONS
Gentamicininjection
Gentamicincream
Gentamicinointments
Gentamicineye drops
BRAND NAMES
Gentimicin
G-mycin
Gentapar
7.NEOMYCIN
1. It is aminoglycosideantibiotic
produced by streptomycesfradiae.
2. It is a broad spectrum antibiotic.
3. It is a mixture of three components
Neomycin A
Neomycin B
Neomycin C

30. PROPERTIES
PHYSICAL PROPERTIES
Colour–white or yellowish-white powder
Nature –hygroscopic
Solubility –
It is freely soluble in water
Very slightly soluble in alcohol
CHEMICAL PROPERTIES
The solution of the substance in pyridine when heated on a water
bath with ninhydrinbetween 65
0
C and 70
0
C for 10 minutes, deep
violet colouris produced.
USES
1. It is a broad-spectrum antibiotic and used to treat
Staphylococcal infections of skin and eye
G I tract infection
2. in conjunction with other antibiotics, it is used to prevent
infection in neutropenicpatients
3. it is also used for the patient suffering from a hepatic coma to
suppress ammonia forming bacteria in G.I tract.

31. PHARMACEUTICAL FORMULATIONS
Neomycin cream
Hydrocortisone and neomycin cream
Hydrocortisone and neomycin ear drops
Neomycin eye drop
Neomycin and hydrocortisone eye drop
Neomycin eye ointments
Neomycin, Bacitracinand polymyxineye
drops
BRAND NAMES
Dexeber-N
Dexacort-N
Ne-Ba-Sulf
Neosporins

32. 8.ERYTHROMYCIN
It is produced by certain strains of streptomyces erythetus
PROPERTIES
PHYSICAL PROPERTIES
Colour –white or yellowish crystals or crystalline powder
Odour –odourless
Taste –tasteless
Nature –hygroscopic
Solubility –
•It is very slightly soluble in water
•Soluble in dilute hydrochloric acid
STABILITY AND STORAGE
It is affected by light, moisture and hence it is stored in tightly
closed light resistant containers at a temperature below 30
0
C
MACROLIDE ANTIBIOTICS

33. USES
1. It is mainly used to treat infections of patients who are allergic to
penicillin like-
•Gonorrhoea
•Syphilis
2. It is also used to treat-
•Pneumonia
•Urethritis
•Pelvic inflammation
3. It is used to treat amoebic dysentery
4. It is also used to treat-
•Wounds
•Burn infections
•Infected eczema
•AceneVulgaris
PHARMACEUTICAL FORMULATIONS
•Erythromycin tablets
•Erythromycin injection
•Erythromycin soluble powder
•Erythromycin estolatecapsules
BRAND NAMES
•Erythrocin
•Althrocin

34. 9.TETRACYCLINES
CHEMISTRY
•7-chlorotetracycline (aureomycin) was the first member among
tetracycline.
•It was introduced in 1947 obtained from streptomyces
aureofaciens
•Two year later, oxytetracycline (tetramycin), produced by
Streptomyces rimosus, was introduced.
•After knowing the structure of chlortetracycline, tetracycline
(Achromycin) was synthesized from it
Tetracyclines are octa-hydro naphthacenederivatives. They are
broad-spectrum antibiotics. Among this class, eight compounds
are introduced in medicine.

35. PROPERTIES
PHYSICAL PROPERTIES
Colour –Yellow crystalline powder
Odour –odourless
Taste –bitter
Solubility –
•It is very slightly soluble in water
•Soluble in dilute acid
•It is soluble in solutions of alkali hydroxides with
decomposition
•Its hydrochloride salt is freely soluble
CHEMICAL PROPERTIES
•At pH between 4 & 8, it undergoes epimerization at C4 that is
inversion of configuration at C4 occurs. The compound thus
obtained has only 5% antimicrobial activity.
•When tetracycline is treated with strong acid, dehydration and
aromatization occur giving anhydrotetracycline.
•In presence of strong alkali, rearrangement and cleavage of the
bond between 11 and 11a occurs giving isotetracycline, a lactone,
which is inactive.

36. STABILITY AND STORAGE
It is stored in the tightly closed, light-resistant container.
USES
1. It has a wide spectrum of activity and it is used to treat –
•Chronic bronchitis
•Urinary tract infections
•Syphilis
•Gonorrhoea
•Rat-bite fever
•Acne vulgaris
2. In conjunction with streptomycin, it is used to treat
plague

37. 3. In combination with fluid and electrolyte replenishers, it is
used to treat cholera
4. In conjunction with quinine, it is used in the management of
malaria
5. In combination with amoebicides, it is used to treat amoebic
dysentery.
6. Topically, it is used to treat chlamydial infection of the eye.
PHARMACEUTICAL FORMULATIONS
•Tetracyclines capsules
•Tetracycline tablets
•Tetracycline injections
•Tetracyclines eye ointments
•Tetracycline and procalineinjection
•Tetracycline intravenous infusion
BRAND NAMES
•Achromycin
•Enterocycline
•Cadicycline

38. 10.CEPHALEXIN
It is β-lactumantibiotics. It different from benzyl penicillin in
having:
•3-methyl, 4-carboxy-3-cephem ring instead of 2, 2-dimethyl, 3-
carboxy penamring
•Amino group at α-carbon of benzyl radical.
PROPERTIES
PHYSICAL PROPERTIES:
Colour –white or cream coloured crystalline powder
Odour –characteristic
Solubility –
•Sparingly soluble in water
•very slightly soluble in alcohol
•very slightly soluble in chloroform
CHEMICAL PROPERTIES
With a mixture of sulphuricacid and nitric acid, it gives a
yellow colour
STABILITY AND STORAGE
It absorbs moisture and is affected by light. Hence, it is stored
in tightly-closed, light-resistant containers at a temperature
not exceeding 30
0
C.

39. CATEGORY
Antibacterial
USES
It is used to treat the following infections due to susceptible
organisms:
•respiratory tract infections
•skin and soft tissue infections
•otitis media
•genitor-urinary infections
•bone and joint infections
•dental infections
PHARMACEUTICAL FORMULATIONS
•cephalexin capsules
•cephalexin tablets
•cephalexin mixture
BRAND NAMES
•sepexin
•neocef
•cephaxin

40. 11.CEPHALORIDINE
It is β-lactumantibiotic. It is different from penicillin in
having:
1. 3-cephem ring instead of penamring.
2. 4-carboxyl and 3-pyridinium methyl groups instead of 2, 2-
dimethyl and 3-carboxylgroup.
3. Thionymethyl group instead of benzyl radical.
PROPERTIES
PHYSICAL PROPERTIES
Colour –white crystalline powder
Odour –odourless
Taste –bitter
Solubility –
•Freely soluble in water
•Very slightly soluble in chloroform

41. CHEMICAL PROPERTIES
With a mixture of sulphuricacid and nitric acid, it gives
permanent bluish-green colour.
STABILITY AND STORAGE
It is discolouredon exposure to light. Hence, it is stored
in sterile tight-closed, light-resistant containers which
are sealed to exclude micro-organism and are kept in a
cool place.
USES
It has a broader spectrum of antimicrobial activity and it
is used to treat:
•Urinary tract infection
•Respiratory tract infections
•Infection of skin
•Infection of soft tissue
•Bone and joint infections
PHARMACEUTICAL FORMULATION
•Cephaloridine injection
BRAND NAMES
•Cephalodine
•Cefadine

42. 12.CHLORAMPHENICOL
CHEMISTRY
•Chloramphenicol is a broad-spectrum antibiotic isolated from
streptomyces venenzuelae( as the organism is collected from
soil sample collected in venenzuela) in 1947 by Ehrlich, et al.
•It is also known as chloromycetin as it contains chlorine atom
and was obtained from actinomycetes spp.

43. •It is the only antibiotic containing p-nitro group; an electron
withdrawing group which is essential for activity.
•Two Hydroxy groups at 1 and 3 positions,
dichloroacetamidogroup at C2 and p-nitrophenyl group at
C1 are attached to propane.
•It contains 2 asymmetric carbon atoms and hence has 4
stereoisomers
•The two structures are threo-isomer and other two are
erythro-isomers.
•Among these 4 stereoisomers, D (-) threo-isomer is
biologically active.
•L-threoand D and L erythroisomersare virtually inactive.
•The absolute stereochemistry at C1 nadC2 is 1R, 2R.
The steric configuration of side chain is virtually important to
antibacterial activity. Similarly, D-threo-1-2-amino-1-phenyl-
propane-1, 3-diol nucleus is essential to antibacterial activity.

44. Chloramphenicol is a substituted D-phenyl serinol. Hence, is
considered as an antibiotic derived from single amino-acid.
CHEMICAL NAME
D(-) threo, 2-(dichloroacetamido), 1-(p-nitro phenyl) propane-1,3-diol.
PROPERTIES
PHYSICAL PROPERTIES
Colour –White or greyish-white or yellowish-white crystalline powder
Odour –odourless
Taste –very bitter taste
Solubility –
•It is slightly soluble in water
•It is freely soluble in alcohol
•Freely soluble in propylene glycol

45. CHEMICAL PROPERTIES
It is hydrolysedby acids or alkali to give dichloroacetic
acid and optically active 2-amino-1-(p-chlorophenyl)
propane-1,3-diol.

46. The hydrolysis is catalyzed by light.
STABILITY AND STORAGE
It is stored in well-closed light-resistant containers.
USES
1. Chloramphenicol is a broad-spectrum antibiotic and is
used to treat –
•Typhoid and paratyphoid fever
•Meningitis
•Urinary tract infections
•Eye infection
•Ear infections
•Skin infections
•Septicaemia(brain abscesses)
Chloramphenicol is more effective when used in
conjunction with ampicillin or Cotrimoxazole than when
used alone.

47. 13. GRISEOFULVIN
PROPERTIES
PHYSICAL PROPERTIES
Colour–White or plan cream colouredpowder
Odour–odourless
Taste –tasteless
Solubility –
•It is very slightly soluble in water
•Soluble in acetone
•Freely soluble in tetrachloroethane
CHEMICAL PROPERTIES
When it is treated with potassium dichromate in presence
of sulphuricacid, wine red colouris produced.

48. STABILITY AND STORAGE
It is stored in tightly closed containers
USES
•It has an antifungal action against a wide range of
dermatophytoses. It gets deposited in the keratin of skin, hair
and nail. Thus, it prevents fungal infection of newly formed
cells
PHARMACEUTICAL FORMULATIONS
•Griseofulvin tablets
•Griseofulvin capsules
•Griseofulvin oral suspensions
BRAND NAMES
•Grisovin
•Blfulvin
•Funglvin

49. 14. CEPHALOTHIN
It different from cephaloridine in having acetoxymethyl
group instead of the pyridinium methyl group at C
3
PROPERTIES
PHYSICAL PROPERTIES
Colour–white crystalline powder
Odour–odourless
Solubility –
•Freely soluble in water
•Practically insoluble in chloroform
STABILITY AND STORAGE
It is affected by light that’s why it is stored in tightly
closed, light-resistant containers, at a temperature not
exceeding 25
0
C.
USES
As under cephaloridine
PHARMACEUTICAL PREPARATIONS
•Cephalothin injections
BRAND NAMES
•Keflin
•Seffin

50. Thank You