ChemistryThe sulfonamides are derived fromsulfanilamideThe sulfonamidestructureissimilartoPABAPABA is P-aminobenzoic acid forthe synthesis of folicacidinbacteria.The amino group(-NH2) of sulfanilamide nucleus mustbe free.SO,NHCOOHNH2NH2Sulfanilamidep-Aminobenzoicacid(PABA)
Chemistry • The sulfonamides are derived from sulfanilamide • The sulfonamide structure is similar to PABA, PABA is P-aminobenzoic acid for the synthesis of folic acid in bacteria. • The amino group(-NH2) of sulfanilamide nucleus must be free. SO2NH2 COOH NH2 NH2 Sulfanilamide p-Aminobenzoic acid(PABA)
Mechanism of actionCOOH1CH2CH2-NH-CHH,NNH2—一SO2NH21COOHOHNPABAPteridineGlulamateSulfonamidescaninhibitdihydropteroatesynthetasebycompetingwithPABAThebacterial DNAsynthesisisdecreasedThe growth of the bacteria can be inhibited
Mechanism of action • Sulfonamides can inhibit dihydropteroate synthetase by competing with PABA . • The bacterial DNA synthesis is decreased. The growth of the bacteria can be inhibited. NH2 SO2 NH2
Action of SulfonamidesPABApteridineglutamateDihydrofolic acidSulfonamidesSynthetaseFolateDihydrofolic acidreductaseTetrahydrofol ateSynthesis ofThymidylate, etc
Action of Sulfonamides PABA (—) Sulfonamides Folate Tetrahydrofol ate Synthesis of Thymidylate, etc. . Dihydrofolic acid synthetase Dihydrofolic acid reduc tase pteridine glutamate
Spectrum of activity. Gram-positive cocci:-Staphylococcus-Streptococcus-PneumococcusGram-negativeBacteria:-Gonococcus-Meningococcus-Y.Pestis-Hemophilus influenzae-Proteus-Escherichia coli-Shigella-K.Pneumobacillus-Pseudomonas:Other susceptible organisms:-Chlamydia-Nocardia-Plasmodium
Spectrum of activity • Gram-positive cocci: - Staphylococcus - Streptococcus - Pneumococcus • Gram-negative Bacteria: - Gonococcus - Meningococcus - Hemophilus influenzae - Y. Pestis - Escherichia coli - Proteus - Shigella - K. Pneumobacillus - Pseudomonas • Other susceptible organisms: - Chlamydia - Nocardia - Plasmodium
Mechanism of resistanceLowered affinity of dihydropteroatesynthase to sulfonamides;Decreased bacterial permeability or activeefflux of sulfonamides;An alterative metabolicpathwayforSynthesis of an essential metabolite or over-production ofPABA.CROSS-RESISTANCE
Mechanism of resistance Lowered affinity of dihydropteroate synthase to sulfonamides; Decreased bacterial permeability or active efflux of sulfonamides; An alterative metabolic pathway for synthesis of an essential metabolite or overproduction of PABA. CROSS-RESISTANCE