Sulfonamides are a group of synthetic antimicrobial agents containing the sulfonamide functional group. The first sulfonamide drug discovered was Prontosil, which is metabolized in the body to sulfanilamide, its active form. Sulfonamides work by competing with para-aminobenzoic acid for the catalytic site of the enzyme dihydropteroate synthetase, inhibiting folic acid synthesis in bacteria. Common side effects include rash, hypersensitivity reactions, and Stevens-Johnson syndrome. Sulfonamides are classified based on their chemical structure and duration of action, and examples include sulfamethoxazole, sulfasalazine, and sulfadimidine.

1. SULFONAMIDES & ANTILEPROTIC
AGENTS
DR. MANJOOR AHAMAD SYED,
M.Pharm,Ph.D
Associate. Professor
Department of Medicinal Chemistry,
College of Public Health and Medical Sciences,
Mettu University, Mettu
Post Box No-318
Ethiopia.

2. SULFONAMIDES
Sulfonamides (sulphonamides) are a group of man-made (synthetic) medicines that contain
the sulfonamide chemical group. They may also be called sulfa drugs. Many people use the
term sulfonamide imprecisely to refer only to antibiotics that have a sulfonamide functional
group in their chemical structure.
The original antibacterial sulfonamides are synthetic (nonantibiotic) antimicrobial agents that
contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity,
e.g., the anticonvulsant (sulthiame). The sulfonylureas and thiazide diuretics are newer drug
groups based upon the antibacterial sulfonamides.

3. HISTORY
The first sulfonamide, trade-named Prontosil, was a prodrug. Experiments with Prontosil began
in 1932 in the laboratories of Bayer AG, at that time a component of the huge German
chemical trust IG Farben.
The first official communication about the breakthrough discovery was not published until
1935, more than two years after the drug was patented by Klarer and his research partner Fritz
Mietzsch.
NH2
N
H2
N
N
SO2NH2
NH2
SO2NH2
Metabolism (in liver)
Prantosil
Sulfonamide
Inactive (in vitro) Active (in vivo)
Notes
 Prontosil - red dye
 Antibacterial activity in vivo (1935)
 Metabolised to active sulfonamide
 Acts as a prodrug
 Sulfanilamide - first synthetic
antibacterial agent acting on a wide
range of infections

5. CHEMISTRY OF SULFONAMIDES:
In 1935, Domagk, a German scientist demonstrated the antibacterial therapeutic property
of Prontosil-an azo dye possessing p-amino-benzene sulfonamide group. He was awarded
Nobel Prize of Medicine in 1939 for his outstanding contribution. The antibacterial activity
of the drug was due to its sulfanilamide component.
Chemically sulfa drugs are amphoteric. They behave as weak organic acid with pKa 4.79
to 8.56. Though they are weakly soluble in water, their solubility is increased at alkaline
pH. Sodium salts are however easily soluble in water. The sulfacetamide is neutral in pH
and is used to combat eye infections.

6. The nitrogen of amino group at para position is designated as N4 while nitrogen of SO2
NH2 is designated as N1. Systemic sulfa drugs are evolved by substitution at N1 position
whereas gut active sulfa drugs are produced by substituting N4 position.
NH2
SO2NH2
(N
4
)
(N1)
NH2
COOH
Sulfanilamide PABA
The basic structure of sulfanilamide and PABA

8. STRUCTURE ACTIVITY RELATIONS: NH2
SO2NH2
(N
4
)
(N1)
1. Sulphanilamide skeleton is the minimum structural requirement for
antibacterial activity.
2. The amino- and sulphonyl-groups on the benzene ring are essential and
should be in 1 and 4 position.
3. The N-4 amino group could be modified to be prodrugs, which are
converted to free amino function in vivo.
4. Sulphur atom should be directly linked to the benzene ring.
5. Replacement of benzene ring by other ring systems or the introduction of
additional substituents on it decreases or abolishes its activity.
6. Exchange of the –SO2NH group by –CONH reduces the activity.

9. STRUCTURE ACTIVITY RELATIONS: NH2
SO2NH2
(N
4
)
(N1)
7. On N-1-substituted sulphonamides, activity varies with the nature of the
substituent at the amino group. With substituents imparting electron-rich
characters to SO2 group, bacteriostatic activity increases.
8. Heterocyclic substituents lead to highly potent derivatives, while
sulphonamides, which contain a single benzene ring at N-1 position, are
considerably more toxic than heterocyclic ring analogues.
9. The free aromatic amino groups should reside para to the sulphonamide
group. Its replacement at ortho or meta position results in compounds devoid
of antibacterial activity.
10. The active form of sulphonamide is the ionized, maximum activity that is
observed between the pKa values 6.6– 7.4.

10. STRUCTURE ACTIVITY RELATIONS: NH2
SO2NH2
(N
4
)
(N1)
11. Substitutions in the benzene ring of sulphonamides produced inactive
compounds.
12.Substitution of free sulphonic acid (–SO3H) group for sulphonamido function
destroys the activity, but replacement by a sulphinic acid group (–SO2H) and
acetylation of N-4 position retains back the activity.
13.Meta-Sulphonamides bind to the basic centres of arginine, histidine, and lysine
sites of proteins. The binding groups are alkyl, alkoxy, and halides. The
binding affects the activity of sulphonamides; protein binding appears to
modulate the availability of the drug and its half-life.
14.The lipid solubility influences the pharmacokinetic and antibacterial activity,
and so increases the half-life and antibacterial activity in vitro.

11. CLASSIFICATION OF SULFONAMIDES
1. BASED ON CHEMICAL STRUCTURE:
(i) Both N1 and N4 substituted sulfonamides - Succinyl sulfathiazole, Phthalyl sulfathiazole
(ii) N-4 substituted sulphonamides (prodrugs): Prontosil.
(iii) N1 substituted sulfonamides - Sulfadimidine (sulfamethazine), sulfamerazine,
sulfaphenazole (Orisul), sulfamethoxazole (Sulfuno), Sulfadimethoxine (Madribon),
sulfacetamide, Sulfaquinoxaline, sulfaethoxypyridazine, Sulfamethoxypridazine,
Sulfasomidine, sulfisoxazole (sulfafurazole), Silversulfadiazine, sulfamylon (Mafenide),
Sulfasimazole, sulfaguanidine etc.
(iv) Miscellaneous: Mefenide sodium.

12. 2. ON THE BASIS OF THE DURATION OF ACTION
(i) Extra-long-acting sulphonamides (half-life greater than 50 h): Sulphasalazine,
Sulphaclomide, Sulphalene.
(ii) Long-acting sulphonamides (half-life greater than 24 h): Sulphadoxine,
Sulphadimethoxine, Sulphamethoxy pyridazine, Sulphamethoxydiazine, Sulphaphenazole,
Sulphamethoxine.
(iii) Intermediate-acting sulphonamides (half-life between 10–24 h): Sulphasomizole,
Sulphamethoxazole.
(iv) Short-acting sulphonamides (half-life less than 20 h): Sulphamethiazole,
sulphaisoxazole.
(v) Injectable (soluble sulpha drugs): Sulphafurazole, Sulphadiazine, Sulphamethoxine.

13. MODE OFACTION:
Sulfonamides compete with para aminobenzoic acid (PABA) for the catalytic site of the
enzyme dihydropteroate synthetase (Woods, 1940) thereby inhibiting conversion of PABA to
folic acid in bacteria. This action of sulfonamide is selective over bacteria without interfering
animal cells.
Antibacterial action can however, be reversed by removal of sulfonamide or addition of
PABA. Bacterial growth is inhibited by bacteriostatic action. Inhibited bacteria can be
eliminated by host defence system preferably by phagocytosis.

16. Active site Active site
Binding interactions
Mechanism of action
Ionic bond
H-Bond
van der Waals
interactions
O
C
O
H2N S
O
O
NR
H2N

17. GENERAL METHOD OF SYNTHESIS FOR SULFONAMIDES:
HNO 3 / H2SO4
NO2
Sn / HCl
NH2
(CH3CO) 2O
CH3COOH
NHCOCH 3
ClSO 3H
NHCOCH 3
SO2Cl
NH3
NHCOCH 3
SO2NH2
H2O / HCl
NH2
SO2NH2
Sulfonamide 4- acetamidobenzene slfonamide 4- acetamidobenzene slfonyl chloride
Acetanilide
Aniline
Nitro benzene
Benzene
Nitration Reduction

18. Side effects:
- Sulfonamides have the potential to cause a variety of untoward reactions, including urinary
tract disorders, haemopoietic disorders, and hypersensitivity reactions.
- When used in large dose, it may develop a strong allergic reaction. One of the most serious is
Stevens Johnson syndrome(or toxic epidermal necrolysis).
- Some of the original sulfonamide drugs were derived from azo dyes and had the interesting
effect of temporarily turning the patient red.
- N.B- Stevens-Johnson syndrome (SJS) is a life-threatening condition affecting the skin, in
which due to cell death the epidermis separates from the dermis. The syndrome is thought
to be a hypersensitivity complex affecting the skin and the mucous membranes.

19. Adverse reactions:
i) The most common manifestation of a hypersensitivity reaction to sulfa drugs are rash and
hives. However, there are several life-threatening manifestations of hypersensitivity to sulfa
drugs, including Stevens-Johnson syndrome, toxic epidermal necrolysis, agranulocytosis,
hemolytic anemia, thrombocytopenia, and fulminant hepatic necrosis, among others
ii) The sulfonamide antibiotic chemical structures are implicated in the hypersensitivity
reactions associated with the class.
- The first is the N1 heterocyclic ring, which causes a type I hypersensitivity reaction.
- The second is the N4 amino nitrogen that, in a stereospecific process, forms reactive
metabolites that cause either direct cytotoxicity or immunologic response.

20. SUCCINYL SULFATHIAZOLE
4-oxo-4-[4-(1,3-thiazol-2-ylsulfamoyl) anilino] butanoic acid
USES:
The drug is used for its antibacterial activity in
the GIT. The dose is 10g - 20g daily in divided
doses.
About 95% of the drug remains in the intestine
and only 5% is hydrolysed, slowly, to
Sulfathiazole and is absorbed.
The Succinyl group is attached to form a
Prodrug for Controlled release of drug
Sulphathiazole.
PHTHALYL SULFATHIAZOLE
USES:
Phthalylsulfathiazole is a broad-
spectrum antibiotic which is part of the
drug class, sulfonamides. It was used as
an antibiotic for bowel surgery, and for
infections of the colon.
2-[({4-[(1,3-Thiazol-2-ylamino) sulfonyl] phenyl}
amino) carbonyl] benzoic acid

22. NH2 NHCOCH3
SO2Cl
+ N
O
N
H2
1. HCl/H2SO4
2. pyridine
N
H2 SO2 NH
N
O
Sulphamethoxazole
aniline
4-(acetylamino)benzenesulfonyl chloride
5-methylisoxazol-3-amine
N
H2 SO2 NH
N
O
Sulphamethoxazole
Sulphamethoxazole
USES:
It is used to treat certain infections, such as:
•Acute exacerbations (worsening) of chronic bronchitis.
•Urinary tract and acute ear infections.
•Shigellosis.
•Diarrhea.
•Pneumocystis jirovecii pneumonia (PCP)
Synthesis:

23. NHCOCH3
SO2Cl
4-(acetylamino)benzenesulfonyl chloride
+
N
N
H2
pyridin-2-amine
pyridine
- HCl
CH3COHN
S
NH
O
O
N
S
NH
O
O
N
N
H2
Sulphapyridine
HCl/H 2O
Sulphapyridine:
USES:
1. Sulfapyridine is a sulfa medicine. It is used to help
control dermatitis herpetiformis (Duhring's disease), a
skin problem. It may also be used for other problems as
determined by your doctor. However, sulfapyridine will
not work for any kind of infection as other sulfa
medicines do.
Synthesis:
S
NH
O
O
N
N
H2
Sulphapyridine

24. NHCOCH3
SO2Cl
4-(acetylamino)benzenesulfonyl chloride
+
N
N
N
H2
pyridine
- HCl
CH3COHN
S
NH
O
O N
N
S
NH
O
O N
N
N
H2
Sulphapyrimidine
pyrimidin-2-amine
NaOH/ H 2O
Sulphapyrimidine:
USES:
1. Sulfapyrimidine is a sulfa medicine. It is used to help control
dermatitis herpetiformis (Duhring's disease), a skin problem.
2. It may also be used for other problems as determined by your doctor.
However, it will not work for any kind of infection as other sulfa
medicines do.
Synthesis:
S
NH
O
O N
N
N
H2
Sulphapyrimidine

25. S
NH2
NH2
O
O
(CH3CO) 2O
S
NHCOCH 3
NHCOCH 3
O
O
HCl/H 2O
S
NH2
NHCOCH 3
O
O
Sulphaacetamide
4-aminobenzenesulfonamide
Sulphacetamide:
USES:
1. Ophthalmic sulfacetamide stops the growth of bacteria
that cause certain eye infections. It is used to treat eye
infections and to prevent them after injuries.
2. It is also used in the treatment of VAGINITIS caused by
Gardnerella vaginalis in combination with other drugs.
Synthesis:
S
NH2
NHCOCH 3
O
O
Sulphaacetamide

26. SULFAMETHIAZOLE
4-amino-N-(5-methyl-1,3,4-thiadiazol-2-yl)-
benzenesulfonamide
USES:
Sulfamethiazole is a drug which is used
for the treatment of urinary tract
infection.
SULFAGUANIDINE
USES:
Sulfaguanidine is a guanidine
derivative of sulfanilamide used in
veterinary medicine. Sulfaguanidine
is poorly absorbed from the gut but
is well suited for the treatment of
bacillary dysentery and other
enteric infections.

27. SULFADIMIDINE (sulfamethazine)
S
NH
O
O N
N
N
H2
Sulfamethiazine
Synthesis:
N
H2
N
N
+
CH3COHN
ClO 2S
4-(acetylamino)benzenesulfonyl chloride
4,6-dimethylpyrimidin-2-amine
(i) Condensation
(ii) Hydrolysis
S
NH
O
O
N
N
N
H2
Sulfamethiazine
USES:
As an aid in the treatment of the
following conditions caused by
bacteria sensitive
to sulfamethazine: foot rot,
shipping fever, bacterial
enteritis/scours, metritis,
mastitis and bacterial
respiratory disease. As an aid in
the treatment of coccidiosis in
sheep.

28. SULFASALAZINE
N
NH
S
O
O
NH
NH
HOOC
O
H
Sulfasalazine
Synthesis:
N
NH
S
O
O
N
H2
sulfapyridine
NaNO 2/HCl
Diazotisation
N
NH
S
O
O
N
Cl
-
N
+
Diazoniumsalt
COOH
OH
Salicylic acid
N
NH
S
O
O
NH
NH
HOOC
O
H
Sulfasalazine
USES:
Sulfadiazine is an antibacterial prescription medicine approved by
the U.S. Food and Drug Administration (FDA) for the prevention
and treatment of certain types of bacterial infections, including the
treatment of chancroid, Toxoplasma gondii encephalitis, urinary
tract infections, and other infections.

29. SULFISOXAZOLE (SULFAFURAZOLE)
S
NH
O
O
N
H2
O
N
Sulfisoxazole
Synthesis:
+
NHCOCH 3
ClO 2S
4-(acetylamino)benzenesulfonyl chloride
(i) Condensation
(ii) Hydrolysis
S
NH
O
O
N
H2
O
N
Sulfisoxazole
N
O
N
H2
3,4-dimethylisoxazol-5-amine
USES:
Sulfisoxazole is used to treat or
prevent infections in many different
parts of the body. It belongs to the
group of medicines known
as sulfonamide antibiotics. It works
by preventing the growth of
bacteria. However, this medicine
will not work for colds, flu, or other
virus infections.

30. SULFADIMETHOXINE (MADRIBON)
USES:
Sulfadimethoxine is a sulfonamide
antibiotic. Sulfadimethoxine is used to treat
many infections including treatment of
respiratory, urinary tract, enteric, and soft
tissue infections. It is most frequently used
in veterinary medicine, although it is
approved in some countries for use in
humans.
4-Amino-N-(2,6-
dimethoxypyrimidin-4-yl)
benzenesulfonamide

31. SULFAMERAZINE
4-amino-N-(4-methylpyrimidin-2-yl)
benzenesulfonamide
Synthesis:
NHCOCH 3
ClO 2S
4-(acetylamino)benzenesulfonyl chloride
+
N
N
N
H2
(i) Condensation
(ii) Hydrolysis
N
N
NH
S
O
O
N
H2
4-methylpyrimidin-2-amine
Sulfamerazine
USES:
Sulfamerazine is a sulfonamide drug that inhibits
bacterial synthesis of dihydrofolic acid by competing
with para-aminobenzoic acid (PABA) for binding to
dihydropteroate synthetase (dihydrofolate synthetase).
Sulfamerazine is bacteriostatic in nature.

32. SULFAQUINOXALINE
4-Amino-N-2-quinoxalinylbenzenesulfonamide
Synthesis:
NHCOCH 3
ClO 2S
+
N
N
N
H2
(i) Condensation
(ii) Hydrolysis
N
N
NH
S
O
O
N
H2
4-(acetylamino)
benzenesulfonyl chloride
quinoxalin-2-amine
Sulfaquinoxaline
USES:
Sulfaquinoxaline is aveterinary medicine which
can be given to cattle and sheep to treat
coccidiosis. It is available in Pakistan with
Sanna Laboratories in combination with
Amprolium and Vitamin K as potential
treatment of coccidiosis.

33. SULFAETHOXYPYRIDAZINE
USES:
Sulfaethoxypyridazine is a sulfonamide
consisting of 6-ethoxypyridazine with a
4-aminobenzenesulfonamido group at the
3-position. Generally licensed for
veterinary use only against bacterial
infections, such as fowl cholera and
salmonella infection. It has a role as an
antibacterial agent.
SILVERSULFADIAZINE
USES:
Silver sulfadiazine cream is used to
prevent and treat wound infections in
patients with second- and third-
degree burns. Patients with
severe burns or burns over a large area of
the body must be treated in a hospital.
Silver sulfadiazine is an antibiotic. It
works by killing the bacteria or preventing
its growth.

34. SULFAMYLON(Mafenide)
USES:
This medication is used alone or with other medications to help prevent and treat wound
infections in patients with severe burns. Mafenide is a drug applied to the skin that belongs
to a class of drugs known as sulfa antibiotics. It works by killing bacteria that may infect an
open wound.
4-(Aminomethyl)benzenesulfonamide

35. CO-TRIMOXAZOLE
Trimethoprim/sulfamethoxazole, also known as co-trimoxazole among other names, is an
antibiotic used to treat a variety of bacterial infections. It consists of one-part trimethoprim
to five parts sulfamethoxazole (1:5).
Cotrimoxazole sequentially block the Dihydropteroate synthase(sulfamethoxazole) and DHFR
(Trimethoprim), in combination they produce broad spectrum of activity and delays the
development of bacterial resistance.
Co-trimoxazole is used to treat certain bacterial infections, such as pneumonia (a lung
infection), bronchitis (infection of the tubes leading to the lungs), and infections of the urinary
tract, ears, and intestines. It also is used to treat 'travelers' diarrhea.

37. H3CO
H3CO
H3CO
CH2 N
N
N
H2
NH2
Trimethoprim
H3CO
H3CO
H3CO
CHO
N
N
Malononitrile
H3CO
H3CO
H3CO
CH2
CH NH2
N
- NH3
N
H2 C NH2
NH
Guanidine
H3CO
H3CO
H3CO
CH2 N
N
N
H2
NH2
Trimethoprim
3,4,5-trimethoxybenzaldehyde
TRIMETHOPRIM
Synthesis:
USES:
1. Trimethoprim is an antibiotic.
It's used to treat urinary tract
infections (UTIs), such as
cystitis.
2. Occasionally, trimethoprim is
used to treat other types
of infections, such as
chest infections and acne.

38. S
NH
O
O
N
H2
N
O
Sulfamethoxazole
+
CH3COHN
ClO 2S
4-(acetylamino)benzenesulfonyl chloride
(i) Condensation w ith pyridine
(ii) Hydrolysis
S
NH
O
O
N
H2
N
O
Sulfamethoxazole
O
N
N
H2
5-methylisoxazol-3-amine
SULFAMETHOXAZOLE
SYNTHESIS:
USES:
Sulfamethoxazole/trimethoprim is
an antibacterial prescription
medicine approved by the U.S.
Food and Drug Administration
(FDA) to treat certain infections,
such as: Acute exacerbations
(worsening) of chronic bronchitis,
Urinary tract and acute ear
infections, Shigellosis, Diarrhea,
Pneumocystis jirovecii pneumonia
(PCP).

39. CO-TRIMAZINE
It is a combination of Trimethoprim and sulfadiazine (1:5). Trimethoprim is selective
inhibitor of bacterial DHFR.
Individually both are bacteriostatic but in the combination they are bactericidal.

40. S
NH
O
O
N
N
N
H2
Sulfadiazine
N
H2
N
N
+
CH3COHN
ClO 2S
4-(acetylamino)benzenesulfonyl chloride
(i) Condensation
(ii) Hydrolysis
S
NH
O
O
N
N
N
H2
Sulfadiazine
pyrimidin-2-amine
SULFADIAZINE:
Synthesis:
USES:
Sulfadiazine is an antibacterial
prescription medicine approved by the
U.S. Food and Drug Administration
(FDA) for the prevention and
treatment of certain types of
bacterial infections, including the
treatment of chancroid, Toxoplasma
gondi encephalitis, urinary tract
infections, and other infections.

41. TRI –SULFAPYRIMIDINES OR TRIPLE SULFA
It consists of sulfadiazine, sulfamerazine and sulfamethazine
S
NH
O
O N
N
N
H2
Sulfadiazine
S
NH
O
O N
N
N
H2
Sulfamerazine
S
NH
O
O N
N
N
H2
Sulfamethiazine
USES:
Triple sulfa is an antibacterial medication. It fights bacteria in the body. Triple sulfa vaginal
is used to treat vaginal infections caused by the bacteria Gardnerella vaginalis. Triple
sulfa vaginal may also be used for purposes other than those listed in this medication guide.

42. Notes
•Amide group lowers the polarity of the sulfonamide
•Amide cannot ionise
•Alkyl group increases the hydrophobic character
•Crosses the gut wall more easily
•Metabolised by enzymes (e.g. peptidases) in vivo
•Metabolism generates the primary amine
•Primary amine ionizes and can form ionic interactions
•Ionised primary amine also acts as a strong HBD
Prodrugs of sulfonamides
HN S
O
NHR2
O
Me
O
H2N S
O
NHR2
O
- CH3CO2H
Enzyme

43. Notes
•R2 is variable
•Different aromatic and heteroaromatic rings are allowed
•Affects plasma protein binding
•Determines blood levels and lifetime of the drug
•Affects solubility
•Affects pharmacokinetics rather than pharmacodynamices
Sulfanilamide analogues
R1
HN S
O
NHR2
O

44. Sulfonamides - Drug Metabolism
Notes
•Sulfonamides are metabolised by N-acetylation
•N-Acetylation increases hydrophobic character
•Reduces aqueous solubility
•May lead to toxic side effects
HN S
O
HN
O
S
N
C
Me
O
H2N S
O
HN
O
S
N
Sulfathiazole Insoluble metabolite
N-Acetylation

45. Sulfonamides with reduced toxicity
Notes
•Thiazole ring is replaced with a pyrimidine ring
•Pyrimidine ring is more electron-withdrawing
•Sulfonamide NH proton is more acidic and ionizable
•Sulfadiazine and its metabolite are more water soluble
•Reduced toxicity
•Silver sulfadiazine is used topically to prevent infection of burns
H2N S
O
HN
O
S
N
Sulfathiazole
H2N S
O
HN
O
N
N
Sulfadiazine
H2N S
O
HN
O
N
N
H2N S
O
N
O
N
N
pKa 6.48
86% Ionized

46. Examples of Sulfonamides
Sulfadoxine
H2N S
O
HN
O
N
N
MeO OMe
N
N
Cl
NH2
NH2
H3C
Pyrimethamine
•Belongs to a new generation of sulfonamides
•Long lasting antibacterial agent
•Once weekly dosing regime
•Sulfadoxine + pyrimethamine = Fanisdar
•Used for the treatment of malaria

47. Examples of Sulfonamides
Sulfathiazole
HO2C
CO2H
H2N S
O
HN
O
S
N
Succinic acid
Enzyme
Succinyl sulfathiazole
Succinyl sulfathiazole
HN
O
O2C
S
O
HN
O
S
N
Notes
•Acts as a prodrug of sulfathiazole
•Ionized in the alkaline conditions of the intestine
•Too polar to cross the gut wall
•Concentrated in the gut
•Slowly hydrolysed by enzymes in the gut
•Used for gut infections

48. Examples of Sulfonamides
Benzoyl prodrugs
Benzoyl prodrug
HN S
O
NHR2
O
C
O
Sulfonamide
Benzoic acid
OH
C
O
H2N S
O
NHR2
O
•Too hydrophobic to cross gut wall
•Slowly hydrolyzed by enzymes in gut
•Used for gut infections

49. ANTILEPROTIC AGENTS

50. ANTILEPROTIC AGENTS
Leprosy is caused by a slow-growing type of bacteria called Mycobacterium leprae (M.
leprae) Also known as Hansen's disease, after the scientist ho discovered M. leprae in 1873
It primarily affects the skin and the peripheral nerves Long Incubation period (3 – 5 years).
Antileprotic drugs are classified as follows:
SULFONES – dapsone (DDS)-Diamino Diphenyl Sulfone
PHENAZINE DERIVATIVE - Clofazimine
ANTITUBERCULAR DRUGS - Rifampicin, Ethionamide
ANTIBIOTICS: Ofloxacin, Moxifloxacin, Minocycline and Clarithromycin

51. SULFONES
Sulfones are primarily used as antibacterial agents and they are less effective than
sulphonamides
•Thought to inhibit dihydropteroate synthetase
•Used in the treatment of leprosy

52. DAPSONE
Synthesis:
USES:
1. This medication is used to treat a certain
type of skin disorder (dermatitis
herpetiformis). It is also used with other
drugs to treat Hansen's disease.
2. Dapsone belongs to a class of drugs
known as sulfones. It works by
decreasing swelling (inflammation) and
stopping the growth of bacteria.
S
O
O
NH2
N
H2
4,4'-sulfonyldianiline
2
H2SO4
Condensation
S
O
O HNO 3 / H2SO4
S
O
O
NO2
O2N Sn/HCl
Reduction
S
O
O
NH2
N
H2
Dapsone(DDS)

53. PHENAZINE DERIVATIVE
MOA:
Interference with template function of DNAAlteration of membrane structure and transport
Disruption of mitochondrial electron transport.
ADRs:
well tolerated Skin: Reddish-black discolouration of skin, discolouration of hair and body
secretions, Dryness of skin and troublesome itching, phototoxicity, conjunctival pigmentation
GIT: Nausea, anorexia, abdominal pain and loose stool (early and late) – dreaded enteritis.
Contraindication: Early pregnancy, liver and kidney diseases.
USES:
Clofazimine is a drug used to treat leprosy. It can slow down the growth and weakly kill
Mycobacterium leprae, the bacteria that cause leprosy. It is used in combination with
rifampicin and dapsone for the treatment of the many forms of leprosy.
CLOFAZIMINE
It is Phenazine dye used as antileprotic, anti-inflammatory and
Bacteriostatic agent.