MOA: Bhave

• ● Bind transpeptidases (PBPs) and block catalysis of crosslinking of peptidoglycan residues resulting in weak cell walls and bacterial lysis if bacteria are actively growing
• ● Bactericidal

• ● Contain b-lactam ring, which:
• → Act as decoy
• → Binding to and inhibit β-lactamases

• ● Cell wall synthesis inhibitor
• → Binds to D-Ala-D-Ala building block of peptidoglycan
• → Blocks transpeptidase binding (peptidoglycan cross linking)

• ● Bactoprenol transfers peptidoglycan subunits to the growing cell wall
• ● Bacitracin inhibits dephosphorylation in cycling of the lipid carrier

• ● Drug is transported to the bacterial cell by glycerolphosphate or glucose 6-phosphate transport system
• ● Inhibits the cytoplasmic enzyme enolpyruvate transferase and eventually inhibits synthesis of N-acetylmuramic acid (NAM)

• ● Lipid portion (tail) of molecule inserts into bacterial cell membrane forming a channel
• → Depolarization of cell membrane
• → Potassium efflux
• → Rapid cell lysis

• ● Inhibits Dihydropteroate synthase from forming dihydrofolic acid
• ● Bacteriostatic

• ● Selectively inhibits bacterial dihydrofolate reductase, which converts dihydrofolic acid to tetrahydrofolic acid, a step leading to the synthesis of purines and ultimately to DNA
• ● Bacteriostatic

• ● Block bacterial DNA synthesis by inhibiting
• → Bacterial topoisomerase II (DNA gyrase- Inhibition of DNA gyrase prevents the relaxation of positively supercoiled DNA that is required for normal transcription and replication)
• → Topoisomerase IV (Inhibition of topoisomerase IV interferes with separation of replicated chromosomal DNA into the respective daughter cells during cell division)

• ● Ribosomal protein synthesis inhibitor (irreversible binding to 30s ribosomal subunit)
• → Block the formation of the initiation complex
• → Miscoding of amino acids in the emerging peptide chain due to misreading of the mRNA
• → Block the translocation on mRNA
• ● Block of movement of the ribosome may occur after the formation of a single initiation complex, resulting in an mRNA chain with only a single ribosome on it, a so-called monosome

• ● Bind reversibly to 30S
• ● Bacteriostatic

Binding to 50S

Binds to the 23S ribosomal RNA of 50S

Binding to 50S

• ● Taken up by diffusion selectively absorbed by anaerobic bacteria and sensitive protozoa
• ● It is non-enzymatically reduced by pyruvate:ferredoxin oxido-reducatase system
• ● Reduced nitroso intermediates from linkages with cysteine bearing enzymes deactivating various cellular enzymes
• ● Metronidazole metabolites are taken up into bacterial DNA, strand breakage, destabilization

• ● Blocks the activity of isoleucyl-tRNA synthetase
• ● Blocks protein synthesis

Reduced by falvoproteins (nitrofurantoin redutase) to multiple reactive intermediates that attack ribosomal proteins, DNA, metabolic processes and other macromolecules

• ● Inhibits synthesis of mycolic acids of the cell wall (FAS II)
• ● [Low] bacteriostatic
• ● [High] bactericidal

• Inhibition of RNA synthesis by binding to the subunit of RNA polymerase (transcription)
• Bactericidal

• ● Inhibits mycobacterial cell wall synthesis by inhibiting arabinosyl transferase
• ● Bacteriostatic

• ● Inhibits fatty acid (FAS I) synthetase, involved in synthesis of short chain mycolic acid
• ● Bacteriostatic and bactericidal

Blocks synthesis of mycolic acid (FAS II)

Inhibition of protein synthesis (blocking translation)

Inhibit folate synthesis (Dihydropteroate synthase preventing synthesis of dihydrofolic acid from PABA)