AntiBacterial

Agent
Mechanisms of antibacterial
action
Inhibition of cell metabolism

Inhibition of bacterial cell wall synthesis

Interactions with the plasma membrane

Disruption of protein synthesis

Inhibition of nucleic acid transcription and replication

Antibacterial agents
against cell
metabolism
Sulphonamides
SAR
the para -amino group is essential for activity and must be unsubstituted (i.e. R 1 = H). Th e
only exception is when R 1 = acyl (i.e. amides). Th e amides themselves are inactive but
can be metabolized in the body to regenerate the active compound ( Fig. 19.5 ). Th us,
amides can be used as sulphonamide prodrugs
the aromatic ring and the sulphonamide functional group are both required;
both the sulphonamide and amino group must be directly attached to the aromatic ring;
the aromatic ring must be para -substituted only. Extra substitution eliminates activity for
steric reasons;
the sulphonamide nitrogen must be primary or secondary;
R2 is the only possible site that can be varied in sulphonamides.
Mechanism of action
The sulphonamides act as competitive enzyme inhibitors of dihydropteroate
synthetase and block the biosynthesis of tetrahydrofolate in bacterial cells
Tetrahydrofolate is important in both human and bacterial cells, because it is an
enzyme cofactor that provides one carbon units for the synthesis of the pyrimidine
nucleic acid bases required for DNA synthesis
Antibacterial agents
inhibit cell wall
synthesis
 N - acetylmuramic acid (NAM)

N - acetylglucosamine (NAG)

Enzyme Transpetidase
SAR Penicillins
 the strained -lactam ring is essential;

the free carboxylic acid is essential.

the bicyclic system is important.

the acylamino side chain is essential;

sulphur is usual but not essential

the stereochemistry of the bicyclic ring with respect to the acylamino side chain is
important.
 variations of the 7-acylamino side chain;

variations of the 3-acetoxymethyl side chain;

extra substitution at carbon 7.

Act on DNA Replication
 The bacterial ribosome is a 70S particle made up of a 30S subunit and a 50S
subunit.
The 30S subunit binds messenger RNA (mRNA) and initiates protein synthesis.

The 50S subunit combines with the 30S subunit-mRNA complex to form a ribosome,
then binds aminoacyl transfer RNA (tRNA) and catalyses the building of the protein
chain.
The ribosomes of eukaryotic cells are bigger (80S), consisting of 60S and 40S
subunits.
Impair Protein Synthesis
Oxazolidinones
Before protein synthesis can start, a 70S ribosome has to be formed by the
combination of a 30S ribosome with a 50S ribosome.
The oxazolidinones bind to the 50S ribosome and prevent this from happening.

As a result, translation cannot even start

Linezolid
Tugas : Hubungan Struktur Aktivitas
Antiinfeksi local
alcohol,halogen
fenol, ammonium kuartener

Anthelmintik
turunan vinilpiperidin
Turunan benzimidazol & turunan kuinolin

Analgetik
Turunan morfin
Turunan asam salisilat
Turunan 5-pirazolidindion
Turunan asam n-arilantranilat
Turunan asam arilasetat
Tugas : Hubungan Struktur Aktivitas
Diuretik
Diuretik penghambat karbonik anhydrase
Turunan tiazida
Turunan asam fenoksiasetat
Turunan sulfamoil benzoate

Sedatif
Turunan barbiturate
Turunan benzodiazepine

Antipsikotik
Turunan fenotiazin
Turunan florobutirofenon
 Halusinogen
Turunan feniletilamin
Turunan asam lisergat

Antituberkulosa
Turunan hidrazida
Turunan amida heterosiklik

Antimalaria (turunan kuinolinometanol)