Sub: Pharmaceutical

Chemistry-II
Topic: Sulphonamides
Definition: Sulphonamides are the antimicrobial compounds containing
sulphonamide group (-SO2NH2).
These are antibacterial compounds, specifically speaking, they are
bacteriostatic.
But occasionally, in very high concentration particularly in the urinary
tract, sulphonamides may act as bactericidal.
Their clinical efficacy and potency are much less than the antibiotics.
General therapeutic uses of Sulphonamides:

Sulphonamides have a wide range of antibacterial activity and are effective against a
variety of Gram +ve and –ve organisms and certain chlamydia organisms causing
trachoma.
The organisms against which sulphonamides are effective are as follows:
1. Some strains of streptococci, staphylococci, pneumococci and meningococci.
2. Clostridia, Bacillus Anthrasis
3. H. influenza, Vibrio cholera, E. coli, Shigella
4. Nocardia, Actinomycetes
5. Chlamydia organisms particularly those causing trachoma
In general, sulphonamides are indicated only in the treatment of urinary tract infections
and in the treatment of meningococcal meningitis.
However, some sulphonamides are used locally eg. Sulphacetamide in eye infections,
Sulphathiazole and sulphaguanidine in intestine etc.
Presence of sulphonamide group in non-antibacterial compounds:
The sulphonamido group is also found to be present in some non-
antibacterial compounds such as some anti-diabetics (chlorpropamide,
tolbutamide), in some diuretics such as Frusemide and thiazides like
hydrochlorthiazide and in some anti-convulsants such as Sulthiame.
Mechanism of action of Sulphonamides:

1. Sulphonamides are the derivatives of the simple compound called Sulphanilamide.

STRUCTURE
2. The compound sulfanilamide exhibits a structural similarly to para amino benzoic acid (PABA), as
observed from their structures…….
3. Due to this structural similarity to PABA, it has been proposed that sulphonamides probably
compete with and substitute PABA in the bacterial metabolism.
REACTION
3. Folic acid derived from PABA in the bacterial cell and it is important in bacterial
metabolism.
4. Due to substitution of PABA by sulphonamides, synthesis of folic acid in the bacterial cell
decreases.
5. Further, Sulfonamides inhibit the enzyme folic acid synthatase which is involved in conversion of
PABA to folic acid.
6. This causes folic acid deficiency, resulting in injury to the
bacterial cell.
7. Such an injured or disrupted bacterial cell can be easily phagocytized.
-Continued
Following observations support this theory:

(i) The antibacterial activity of sulfonamides is confined only of those

micro organisms which synthesise their own folic acid.
(ii) Sunfonamides are ineffective in presence of pus & tissue breakdown
products which contain a large amount of PABA. Similarly some drugs
which yield PABA in the body after biotransformation antagonize the
sulfonamide action eg. Procaine, Amethocaine and Procainamide.
(iii) The bacteriostatic action of sulfonamides can be countered by PABA.
(iv) Sulfonamide resistant microorganisms often show an enhanced PABA
synthesis.
Classification of Sulphonamides
They can be classified in following different ways:
i) Classification based on site of action:
1) Sulphonamides used in eye injection eg. Sulphacetamide
2) Sulphonamides used for intestinal infection eg. Sulphaguanidine,
Phthallyl sulphathiazole
3) Sulphonamides used for systematic infection eg. Sulphadiazine,
Sulphadimidine, Sulphamethazine, Sulphaisoxazole, Sulphathiazole,
Sulphapyridine
4) Sulphonamides useful in burn infection eg. Silver sulphadiazine
5) Sulphonomides used in urinary tract infection eg. Sulphaphenazole,
Sulphapyrazole, Sulphamethizole, Sulphamethoxazole, Co-trimoxazole
ii) Pharmacological Classification:
1) As antibacterial eg. Sulphacetamide, Sulphadimidine, Sulphadiazine,
Sulphaphenazole
2) As oral hypoglycemic eg. Chlorpropamide, Tolbutamide
3) As diuretic eg. Furosemide, Acetazolamide
4) As antimalarial eg. Sulphadoxine
5) As antidiarrhoeal eg. Phthalyl sulphathiazole, Sulphaguanidine
iii) Based an Duration of Action :
1) Long Acting – (t/2 of about 24 hours) eg. Supha methoxy pyridazine
2) Intermediate Acting – (t/2 between 10-12 hours) eg. Sulphamethoxazole
3) Short Acting – (t/2 less than 10 hours) eg. Sulphathiazole, Sulphaisoxazole

iv) Chemical Classification:

Suphonamides having-
1) Substituents on aromatic amino group eg. Prontosil
2) Substituents on Sulphonamido Nitrogen eg. Sulphadiazine, Sulphamethoxazole
3) Substituents on both amino and Sulphonamido group eg. Phthalyl sulphathiazole,
Succinyl sulphathiazole
4) Sulphonamides without aromatic amino group eg. Mefenide
Compounds
Sulphacetamide :
 
 
 

Properties:
1. It occurs as white crystalline powder.
2. It possesses an acid and slightly saline taste.
3. Soluble in water & alcohol.
4. As soln is acidic in nature.
5. It is soluble in mineral acid & solutions of alkali hydroxides.
6. Insoluble in organic solvents.
7. Should be stored in tightly closed containers, protected from light.
Uses : useful in treatment of urinary tract infections

 
 

 
Sulphacetamide sodium
1. Occurs as yellowish white to white, crystalline pdr.
2. odourless c a slightly filter taste.
3. Slowly darkens on exposure to light .
4. solute in water & alcohol, insoluble in organic solvents, .
5. The solution for injection is sterilized by autoclaving.
Structure:
Uses :
1. It is a Sulphonamide possessing antibacterial activity.
2. Used mainly by local application in the infections or injuries of eyes.
3. Used in treatment of acute conjunctivitis and in the prophylaxis of ocular infections after injuries or burns.
Official Preparations:
Sulphacetamide Sodium, B. P., I. P.
Sulphacetamide Sodium Eye Ointment, B. P., I. P.
Sulphacetamide Sodium Eye drops, B. P.
Supphadiazine :
 

   N1 (2- Pyrimidinyl) sulphanilamide.

Properties:
1. White to yellouish white oourless, tasteless crystal powder.
2. Slightly soluble in water & insoluble in org. solvents like ethyl, CHCL3
3. soluion in dilute mineral acids & solution of alkalic hydroxide.
4. Sterilized by autoclaving or filtaration.
Official also as the Sodium salt which occurs as white crystalline odourless, tasteless powder, soluble in water, insoluble in organic solvents.
Action and Uses:
5. Used in systematic bacterial infections.
6. Useful in meningococcal meningitis and pneumococcal infection influence etc.
Official Preparations:
Sulphadiazine, B. P., I. P.
Sulphadiazine injection, B. P., I. P.
Sulphadiazine Tablets, B. P., I. P.
Sulphadiazine sodium, B. P.
Sulphadiazine sodium injection, B. P.
 
Sulphaguanidine :

 
Properties:
1. White, odourless, tastless cryst pdr.
2. Slightly soluble in H2O, Insoluble in ethyl and acetone.
3. Soluble in dilute mineral acids and insoluble in alkali hydroxide solutions.
Strc.
 
Action and Uses :
1. Used in treatment of local intestinal infection, particularly bacillary dysentery.
Official Preparations–
Sulphagunidine, I. P.
Sulphagunidine Tablets, I. P.
Phthalyl Sulphathiazole :
Properties:
1. White to yellowish white, odourless, crystalline powder.
2. Insoluble in water. CHCl3, ethyl. Soluble in alkali hydroxide solution and of soluble
of , and in dilute solution of HCl. Slightly…….
  
Strc.
 
Action and Uses: used for iti antibacterial activity in the g.i.t used in treatment of
basically dysentery. Also used in chronic alcenative colostics & intestinal amoerianis
Official Preparations:
Phthalyl sulphathiazole, B. P., I. P.
Phthalyl sulphathiazole Tablets, B. P., I. P.
Succinyl sulphathiazole:
MKT – chemostrep sultasxidine
Properties:
1. White to yellowish white, odourless, crystalline powder with a slightly
bitter taste.
2. Slightly soluble in water and insoluble in organic solvents. Soluble in orange
solution alkali hydroxide & carbonate
Str.
 
Action and Uses: for intestinal infection. Ulcerative colitis
IP
Tab , IP
Sulphadimethoxine
Str.
White to creamy whitecryst, odourless, tasteless powder slightly soluble in H2O,
insoluble in orange solvent like ethyl & ahcl3 soluble in dilute mineral acids & in
soluble of alkalic hydroxide & carbonales.
Str.

Action and Uses: Long acting sulphonamide with general properties of

sulphonamides. Used in various systemic infections.
Official Preparations:
Suphadimethoxine, B. P., I. P.
Suphadimethoxine Tablets, B. P., I. P.
• sulphamethxypyridazine :
• occurs as white to yellowish white, odourless, tasteless, crystl pdr. Slightly soluble in
water, practically insoluble in ethyl soluble in dilute mineral acids & soluble of alkali
hydroxides. Solution may be sterilized by filtaration & distributed in sealed certains ,
the air in which is replaced
• str.
• 
• Uses : long acting sulphonawide, used for u.t. infectionalso in systematic infection
• Off : sulphamethoxy pyridazine BP
• sulphamethoxy pyridazine tab, BP
• 
• sulphamethxazle :
• 
• occurs as white to yellowish white, odourless, cryst pvr c a slightly filter taste. Slightly soluble in watersoluble in acetone, insoluble in
ethyl & ahcl3 . freely soluble in solution of alkali hydroxides.
• Str,
• 
• 
• 
• Uses :
• Principally used in u.t.i
• Usually used in combination with trimethoprim for its antibacterial action
• Off : sulpharmethoxazole, IP. BP
• Cotrimoxazole injection, BP
• Cotrimoxazole tab, BP
• Dispensible cotrimoxazole tab BP
• Paediatric cotrimoxazole tab, BP
• Sulpharmethaxazole, I.P
• Trimethoxazole & sulpha methaxazole oral IP.
• Trimethoxazole & sulpha methaxazole Tablets IP.
• 
• Co-trimoxazole :
• Co -trim trimoxazole is a mixture of 5 parts of sulpharmethoxazole & 1 part of
trimethoprim.
• The two components of cotrimoxazole interface c the bacterial inthesis of tutraydrofolic
acid, essential solutions of nuclear acids. Sulpharmethoxazole institute the synthesis of
dihydroxide folic acid from PABA. Trimethoprim intibill the action of dihydrofolate reduclace &
prevent the synthesis a tetrahydrofolic acid from dihydrofolic acid. When the two are used
, enhanced antibacterial activity is .
• 
• Uses :
• Used similarly to sulphonamides in a wide range of infection. Mainly used in a u.t.I & large
tract infection. The combination is also
• Dispusible to trimoxozole tab, BP
• Paediatric co- trimoxazole. Tab , BP
Structure Activity relationship among different Sulphonamides
• Chemistry : The simplest of the sulfonacides is suffanilamide
• Structure
•
• 
• The p- aonio group is essential & can be replaced by such radicals as can be converted in the tissues to
free amino group.
• Many Derivatives of sulphoracide having subshitments in place of hydrogen of the sulphorscide
group (-So2NH2) are successful in mecdicine.
• Subotitutions made in the quide NH2 group (N1) have variable effect an antibacterial activity of the
molecule.
• Substitutents like heliocyclic anomatic nucli at N1- have given highly potent compounds. Generally
N1- substituted compound are 2-6 time mareacite.
• Pyrimidine derivatives (1,3 – diazine) are highly successful egs. Sulphadiazine, Sulphadiacide
(sulphamithazine) sulphasomidine , sulphadiamethoxine ( sulphamethoxine).
• 
• Structure
• The substitutions at N1 with s – membered hatenocyes containing 2 or more heles atoms (azoles)
gave compound c gond activity. Sulphethizole c is N1 thiazol -2- glsulphanilamide is one of the very
early helesocyclic compounds of intend. It’s derives phthalyl & succinly sulphathiazole are official
• Structure
• 
• 
• 
• Another such helinocyclic ring is isoxazole c is present in sulphatunazole ( sulfisoxoze) &
sulphamethaxazole.
• In sulphamethoxazole, the p- aniobenzene sulpharacides pro is attached to position 3 of
isoxazole, whereas in sulphaturazole, the pt. of sulphonami to attachment is positions.
• 
• Sulphacetamide is a compound when the substitutes at N1 of sulphanilamide
is relatively simple like acetyl group & sulphaguaridine contain amidine
(guaryl) group.
• Sulphonamides are white or nearly white crystalline powders. They are
stored in well closed higth resistance conteneous . sulphonawides are very
highly soluble in water but their sodium salts are freely soluble. The officials
sodium salts are sulphadimidine sodium & sulphavcetamide sodium.
• 
• 
• 
Co-trimoxazole
Co-trimoxazole is a 5:1 mixture of Sulphamethoxazole and Trimethoprim.
MOA of Co-trimoxazole:

PABA
Folic acid synthatase
Folic acid
Sulphamethoxazole
DHFA
Trimethoprim Dihydrofolate synthatase
THFA

Bacterial Nucleic acid

MOA continued-

1. The two components of Co-trimoxazole interfere with the synthesis

of tetra hydro folic acid (THFA), which is an essential step in the
synthesis of bacterial nucleic acids.
2. As can be observed from the schematic diagram given in the last
slide, Sulphamethoxazole inhibits the synthesis of di hydro folic acid
(DHFA) from PABA (para amino benzoic acid).
3. Another component Trimethoprim inhibits the synthesis of THFA
from DHFA by its inhibitory action on the enzyme di hydro folate
reductase.
4. Therefore the combination of Sulphamethoxazole and Trimethoprim
provides enhanced antibacterial ativity possessing a very broad
spectrum of antibacterial action.
Advantages of Co-trimoxazole:
Co-trimoxazole offers some advantages over it’s individual components
viz. Sulphamethoxazole and Trimethoprim
1. When these two compounds are used together, an enhanced
antibacterial action is reported.
2. The antibacterial spectrum of activity is widened because of their
synergistic action. The additional organisms covered by this
combination include S. typhi, Klebsiella
 Differentiate between Sulphonamides and Sulphones:

Sr. No. Sulphonamides Sulphones

1 Sulphonamides are the derivatives of These are the compounds having ‘Sulphone’
Sulphanilamide group.

2 They possess strong bacteriostatic action and These compounds possess a limited
are used for prevention and treatment of of antibacterial action (such as antileprotic) and
different types of bacterial infections in some sulphones may have antimalarial
human beings. activity.

3 These compounds can be represented by the The structure of most commonly used
general formula: sulphone, Dapsone is …….
R-NH-C6H5-SO2NH-R’

4. They are available in different range of No such different sulphones are available.
activity such as Long acting, Intermediate
acting, Short acting.
Brand names:
Sr. Sulphonamide Brand Names
No.

1 Sulphacetamide Albucid, Nebasulf

2 Sulphadiazine Antrima

3 Phthallyl sulphathiazole Thalazole

4 Succinyl sulphathiazole Thiacyl

5 Sulphamethoxazole Bactrim, Ciplin

6 Co-trimoxazole Bactrim, Cotrimox, Septran,

Questions
1. What are Sulphonamides, give examples.
2. Give general therapeutic uses of Sulphonamides.
3. Explain the mechanism of action of Sulphonamides.
4. Classify Sulphonamides in different ways, giving suitable examples under
each class.
5. Give structure, chemical name, properties, uses, official preparations and
popular brand names of Sulphacetamide.
6. Give structure, chemical name, properties, uses, official preparations and
popular brand names of Sulphaguanidine.
7. What is Co-trimoxazole, give its composition. Also give its mechanism of
action, uses, advantages over individual components, official preparations
and popular brand names.
8. Differentiate between Sulphonamides and Sulfones, giving examples.
9. Discuss the Structure Activity relationship (SAR) in different Sulphonamides.