Dugga 3 - Antibacterial Flashcards
Is vancomycin used on gram negative bacteria?
No, because vancomycin is such a large molecule it is unable to pass the outer cell membrane.
What are the 5 main strategies that antibacterial drugs is developed from?
- Antimetabolites = inhibition of the cell metabilism. Ex inhibit an enzyme-catalyzed reaction present in a bacterial cell
- Inhibition of bacterial cell wall synthesis
- Interactions with the plasma membrane
- Disruption of protein synthesis
- Inhibition of nucleic acid transcription and replication
Vancomycin uses dimerization and through that sterically hindering the two enzymes to interact with the L-lys-d-Ala-d-Ala tail of the cell wall building block, which ones?
Transglycosidase - catalyzes the attachment of the disaccharide building block to the growing cell wall.
Transpeptidase enzymes - the enzyme is responsible for the crosslinking between the various chains of the cell wall
What is two factors important for vancomycins rigdification and specification?
Fixed conformation of hexapeptide chain.
The aromatic rings are prevented from becoming coplanar
Mention some analogues to vancomycin
- Teicoplanin
-Dalbavancin
Glycopeptides are slow in causing resistance in bacteria, why?
Attack bacteria in three different ways:
- Block enzymes by acting as a steric sheild for the tail of the cell wall building block’s pentapeptide moeity
- RNA synthesis is distrupted
3.
What is an ionophores?
A drug that enables, allows unctrolled movement of ions across the cell membrane.
Have killer nano tubes reached the market?
No
How is disruption of protein synthesis carried out?
Mention some drugs groups that does this:
By binding to ribosomes and inhibiting different stages of the translation process
- Aminoglycosides (30S unit in a way that mRNA is hindered)
- Tetracyclines (30S unit -in a way that it inhibits tRNA from binding)
- Chloramphenicol (Asite of the 50S subunit inhibit movement along mRNA)
- Macrolides (50S unit)
- Lincoasmides
- Streptogramins
- Oxazolidinones - prevents interaction between the 50unit and the 30unit
- Pleuromutilins
Bacterial ribosomes is made up out of subunits, how many?
70S = 30S and 50S
What is an example of an aminoglycosides
Streptomycin
Aminoglycosides are bactericidal, true of false?
True
What are AMEs
Aminoglycoside modifying enzymes, weakens the Aminoglycoside affinity to the binding site of the 30S in ribosomes
Resistance against aminoglycosides
- Structural changes in the outer membrane of gram negative bacteria
- Efflux pump
- Membrane proteases
Agents that act on nucleic acid transcription
- Quinolones and fluoroquinolones
- Spiropyrimidinetriones
Antibodies
Drug resistance
- by mutation
- by genetic transfer
- ## Other factors affecting drugs resistance
What is MRSA
Bacterial that has developed a resistance to B-lactam resistant enzymes. This is due to mutations in their transpeptidase enzyme.
What are the qualities of good broad spectrum penicillins?
Broad spectrum penicillins must be able to target gram negative bacteria aswell. They should therefor be able to:
- They must cross the outer membrane of gram negative bacteria
- Not be suseptible to B-lactamase (steric sheild)
- Has a high affinity to transpeptidase enzyme
- Has a low rate of being pumped out of the bacterial cell, specially important for gram negative bacteria.
What are three b-lactamase resistant penicillins?
- Meticillin
- Nafcillin
- Oxacillin
What side chain variations was tested in order to find broad spectrum drugs? and what was their effect
- Hydrophilic side chains in alfa position
What are good side chains for targeting G-negative bacteria
- Hydrophilic side chain. This is because of the porins, in able to pass the porins the size, structure and charge are essential.
Negatively charged side chains, hydrophobic and large are BAD for the drugs ability to pass the outer lipopolysaccharide membrane. - Good hydrophilic groups are (NH2, OH, CO2H)
- The hydrophilic group should be in the alfa position to the carbonyl group of the side chain, in other words close.
What kind of drug is sulfanomide? How does it work?
Antimetabolite.
Competative inhibitor of an enzyme that catalyzes production of tetrahydrofolate. Tetrahydrofolate is a cofactor in the synthesis of pyrimidine nucleic acid, which is important in DNA synthesis.
What is important in the structure of analogues of sulphonamides?
- Para-amino group is important for activity. R1 must be H.
- R1= acyl is accetable since it can be metabolitzed in the body
- Aromatic ring and sulphonamide is essential.
- Sulphonamide and amino group must be directly attached to the aromatic ring
- Aromaric ring must be in para position only! Due to steric reasons.
- Sulphonamide nitrogen must be primary or secondary only. This is due to its need to be HBD.
- R2 is the only possible site that can be varied.
