Sulfonamides were the first drugs effective against pyogenic (production of pus) bacterial infections. Observed in the sulfonamido-chrysoidine (Prontosil Red) dye by Domagk. 
 

Classification

Short acting: Sulfadiazine
Intermediate acting: Sulfamethoxazole
Long acting: Sulfadoxine, Sulfamethopyrazine
Special purpose: Sulfscetamide Sodium, Sulfasalazine, Silver sulfadiazine, Mafenide

Uses

        Meningitis
        Streptococcal pharyngitis
        Sulphamethoxazole + Trimethoprim (Cotrimoxazole) is used for many bacterial infections & P.jiroveci.
        Conjunctivitis - Sulfacetamide Sodium
        Prevent infection on burn surfaces - Silver Sulfadiazine (topical)

Mechanism of Action

        Sulphonamides are structural analogues of PABA. Thus inhibit bacterial folate synthase, Folic acid is not formed and a number of essential metabolic reactions suffer.

Note: Only those microbes which synthesize their own folic acid and cannot take it from the medium are susceptible to sulfonamides.

Adverse Effects

        Nausea, Vomiting and epigastric pain.
        Crystalluria (dose related) - Occurs due to acetylated derivatives of sulphonamidea are not soluble in urine.
        Hypersensitivity reactions
        Kernicterus (new born)

Structure - Activity Relationship

General Structure

        - Sulfonamides are derivatives of sulfanilamide - para-amino benzene sulfonamide.
        - Differs in the N1 substitution  of sulfanilamide.

Sulphonamides

SAR

        • Amino (-NH2) group should be in 4th position and Sulphonyl (-SO2) group should be in the 1st position. Essential for activity.
         N-4 amino group could be modified to be pro-drugs.
         Replacement of benzene ring by other ring system decreases or abolishes activity.
         Substitutions on benzene ring decreases activity.
        • Substituents imparting electron-rich characters to SO2 group, on N-1, increases bacteriostatic activity.