This sulphonamide and Sulfone will be helpful to the students of Pharmacy specially in the subject of Medicinal Chemistry.

1. Sulphonamides and
Sulfones
Prepared By: Navdha Soni
Asst. Professor
L.J. Institute of Pharmacy
Ahmedabad

2. Introduction
• Sulphonamide is a class of organic compounds that are amides of sulphonic acids, some of
which are sulpha drugs and act as powerful inhibitors of bacterial activity.
• In 1935, it was discovered that a red dye called prontosil red had antibacterial properties
in vivo (i.e. when given to laboratory animals).
• But no antibacterial effect was observed in vitro.
• Later it was discovered that prontosil red was metabolized by bacteria present in the small
intestine of the test animal to give a product called sulphanilamide.
Prontosil Red
(Inactive)
Sulphonamide
(Active)
Metabolic cleavage

3. • The agent contains sulphonamide group(-SO2NH2) called para amino benzoic
sulphonamide.
• Chemically sulpha 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.
• They are white crystalline powder.
• (- SO2NH2) group present in sulphonamide is not essential but the important feature is
that the sulphur is directly linked to the benzene ring.
• The para NH2 is essential for antimicrobial activity of sulphonamide.
• Sulphonamide is the structural analogue of para amino benzoic acid(PABA).
• It inhibits bacterial folic acid synthesis(competitor of PABA).
Chemistry of Sulphonamides

4. • Folic acid is essential for the growth of bacteria. It
is a precursor of purine synthesis and this purine
is require for the synthesis of DNA & RNA.
• Para amino benzoic acid(PABA) is a precursor of
folic acid and sulphonamide has structural
similarity to PABA.
• In this bacteria, sulphonamide compete with the
PABA for the enzyme folic acid synthetase and
prevent the incorporation of PABA into folic acid,
so folic acid is not synthesized. As a result bacteria
are deprived of folic acid and are unable to
multiply.
Mechanism of Action
P-Aminobenzoic Acid
Dihydrofolate
Tetrahydrofolate
Nucleic acid synthesis
Dihydropteroate
Synthetase
Dihydrofolate
Reductase
Sulfonamides
Trimethoprim

5. • Sulphonamides are active against
Gram-positive and gram-negative
bacteria.
• It is also active against Nocardia,
chlamydia trachomatis, some
protozoa.
Antibacterial activity

6. Classification Depending Upon Duration
Short acting sulphonamide
Sulfamethiazole Sulfisoxazole

7. Classification Depending Upon Duration
Intermediate acting sulphonamides
Sulfamethoxazole Sulfamoxole

8. Classification Depending Upon Duration
Long acting sulphonamides
Sulfadimethoxine Sulfamethoxydiazine

9. Classification Depending Upon Duration
Extra long acting sulphonamides
Sulphasalazine Sulfalene

10. Other Sulphonamides
Sulfamethazine
Sulfapyridine
Sulphacetamide

11. Sulphadiazine Mefenide acetate
Other Sulphonamides

12. Structure activity relationship
The major features of SAR of sulphonamides include:
a. Sulphonamide skeleton is the minimum structural requirement for antibacterial
activity.
b. Sulphur atom should be directly linked to the benzene ring.
c. In N1 substituted sulphonamides, activity varies with the nature of the substituent at
amido group. With substituents, impairing electron rich character of SO2 group,
bacteriostatic activity increase. Heterocyclic substituents leads to highly potent
derivatives.

13. Structure activity relationship
d. Sulphonamides that contain a single benzene ring at N1 position are considerably more
toxic than heterocyclic ring analogs.
e. The free aromatic amino group sholreside para to the sulphonamido group. Its
substituents at ortho and meta position results in compounds devoid of antibacterial
activity.
f. The presence of free amino group is very essential for the activity. Any substituents of
amino group either results in prodrug nature or in the loss of activity. Ionized form of
sulphonamide is active.(pKa- 6.6-7.4)
g. Substituents of free sulphonic acid (-SO3H) group for sulphonamide function, destroys
the activity but replacement by sulfinic acid group (-SO2H) and acetylation of N4
position retains the activity.

14. Therapeutic uses
• Urinary tract infections.
• Upper respiratory tract infections.
• Nocardiosis.
• Sulfasalazine in IBD.
• Sulfacetamide in bacterial conjunctivitis & trachoma.
• Silver sulfadiazine for prevention of infection of.
• burn wounds.

15. Adverse effects
• Hypersensitivity reactions
• Crystalluria, hematuria, renal obstruction.
• Allergic nephritis
• Haemolytic anaemia, aplastic anaemia, thrombocytopenia.
• Kernicterus in new born

16. Trimethoprim – Sulfamethoxazole
combination (Co-trimoxazole)
Sulphamethoxazole Trimethoprim
Mechanism of action:
• Sequential blocking of purine synthesis (synergism).
• Trimethoprim inhibits dihydrofolate reductase enzyme so inhibits tetrahydrofolic acid
synthesis.
• The combination is bactericidal.

17. Clinical Uses
• Acute or Complicated or recurrent urinary tract Infections especially in females
• Upper respiratory tract infections
• Pneumocystis jiroveci pneumonia
• Toxoplasmosis
• Shigellosis
• Nocardiosis
• Typhoid fever
• Salmonella infections
• Prostatitis
• Community –acquired bacterial pneumonia

18. Adverse effects
• Megaloblastic anemia, leukopenia & granulocytopenia (can be prevented by
administration of folic acid).
• All side effects associated with sulphonamides.

19. Sulfone
• Dapsone also known as diaminodiphenyl sulfone (DDS) is an antibiotic commonly used in
combination with rifamoicin and clofazimine for the treatment of leprosy.
• Side effects may include a decrease in blood cells, red blood cell breakdown.
Dapsone

20. Thank You