Sulfonamides

ANTIBACTERIALS

Photo by Edgar181 / Public domain

 The term sulphonamides are employed as a generic name
for the derivatives of para amino benzene
sulphonamide(sulphanilamide).

The sulphonamide drugs were the first effective

chemotherapeutic agents to be employed systemically for
the prevention and treatment of bacterial infections in
INTRODUCTI humans.

ON The sulphonamides are bacteriostatic antibiotics with a

wide spectrum action against most gram-positive bacteria
and many gram-negative organisms.

Actually it was found to be the metabolic product of

Prontosil, which is responsible for antibacterial activity, and
this has given the initiation to develop sulphonamides as
antibacterial agents.
Discovery

• Domagk (1935) , testing over 1000 azo dyes synthesized by the Bayer laboratories,
demonstrated outstanding anti-streptococcal and staphylococcal activity for the
sulf-amido azo dye prontosil in mice. The drug was introduced into clinical
medicine on the basis of successful animal experimentation. The curious puzzle
that prontosil had no effect on bacterial growth in culture were solved by urine
analysis of patients treated with prontosil, showed that most of the drug was
excreted with azo linkages yielding the compound P-amino benzene sulphonamide
(Sulfanilamide)
 Sulphonamides are total synthetic substances that are produced
by relatively simple chemical synthesis.

SULPHONAMID The advent of penicillin and, subsequently of other antibiotics has

ES: diminished the usefulness of sulphonamides.

Antimicrobial compounds contain sulphonamide (SO2NH2) group.

This group (SO2NH2) is also present in other compounds, such as
antidiabetic agents (e.g. Tolubutamide), diuretics (e.g.
chlorthiazide and its congeners,furosemide, and acetazolamide),
and anticonvulsants such as sulthiame
 On the basis of the chemical structure

N-1 substituted sulphonamide: Sulphadiazine, Sulphacetamide,

Sulphadimidine.

CLASSIFICATI N-4 substituted sulphonamides (prodrugs): Prontosil.

ON
Both N-1 and N-4 substituted sulphonamides: Succinyl
sulphathiazole, Phthalylsulphathiazole.

Miscellaneous: Mefenide sodium.

 On the basis of the pharmacokinetic properties

• Poorly absorbed sulphonamides (locally acting sulphonamides)

—Sulphasalazine, Phthalylsulphathiazole,
CLASSIFICATI
ON: • Rapidly absorbed and rapidly excreted (systemic
sulphanamides): Sulphamethoxazole, Sulphaisoxazole,
Sulphadiazine, Sulphadimidine, Sulphafurazole, Sulphasomidine,
Sulphamethiazole, Sulphacetamide

• Topically used sulphonamides: Sulphacetamide, Mafenide,

Sulphathiazole, Silver sulphadiazine.
 CLASSIFICATION:

I. N-1 Substituted
sulphonamides:
CLASSIFICATION:

a. Short-acting sulpha
drugs:
CLASSIFICATION:

b. Intermediate-acting
sulphonamides:
CLASSIFICATION:

c. Long-acting
sulphonamides:
CLASSIFICATION:

II. N-4 substituted sulphonamides:

CLASSIFICATION:

III. Both N-1 and N-4

substituted sulphonamides
SYNTHESIS:

I. N-1 Substituted
sulphonamides
i. Sulphanilamide
 Nitration Reduction Acetylation

Acid
Hydrolysis

Sulphonation Amination
 RELATED SULPHONAMIDES SYNTHESIS :

SULFADIAZINE

SYNTHESIS SULFAMETHOXAZOLE

:
From book SULFISOXAZOLE

SULPHASALAZINE

SULFACETAMIDE & SULFATHIAZOLE

 On N-1-substituted sulphonamides,

SULPHONAMIDES SAR:
activity varies with the nature of the
substituent at the amino group.
With substituents imparting electron-
Sulphanilamide skeleton is the
The N-4 amino group could be rich characters to SO2 group,
minimum structural requirement for
modified to produce prodrugs, bacteriostatic activity increases.
antibacterial activity.
which are converted to free amino
function in vivo.

The free aromatic amino

groups should reside para to
the sulphonamide group. Its The amino- and sulphonyl-groups
replacement at ortho or meta on the benzene ring are essential
position results in compounds and should be in 1 and 4 position
devoid of antibacterial activity.

Substitutions in the benzene ring of sulphonamides Heterocyclic substituents lead to highly

produced inactive compounds.
Sulphur atom should be directly
linked to the benzene ring.
potent derivatives, while
sulphonamides, which contain a
single benzene ring at N-1 position, are
considerably more toxic than
heterocyclic ring analogues.
 SULPHONAMIDES SAR
Replacement of benzene ring by other ring systems or the
introduction of additional substituents on it decreases or
abolishes its activity.

Exchange of the –SO2NH group

by –CONH reduces the activity.

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.
The lipid solubility influences the
pharmacokinetic and antibacterial activity, and
so increases the half-life and antibacterial
activity in vitro.
MECHANISM OF ACTION:
M.O.A:
THERAPEUTIC APPLICATIONS: