沈阳药科大学《药物化学》PPT教案_抗生素(Antibiotics)

Antibiotics Antibiotics are microbial meta bilites or synthetic analogs inspired by them that, in small doses, inhibit the growth and survival of microorganism In clinic the antibiotics are used to be antibacterial mainly, but in recent year, they can also be used for anti-cancer, anti viral, enzyme-inhibitors, and receptor-antagonist

Antibiotics Antibiotics are microbial metabilites or synthetic analogs inspired by them that,in small doses, inhibit the growth and survival of microorganism. In clinic the antibiotics are used to be antibacterial mainly,but, in recent year, they can also be used for anti-cancer,anti￾viral ,enzyme-inhibitors, and receptor-antagonist

Classification (According their structures) 1Beta- Lactam antibiotics(β-内酰胺类) 2 Tetracylines antibiotics(四环素类) 3 Aminoglycoside antibiotics(氨基糖甙类) 4 Macrolides antibiotics(大环内酯类) 5. Others

Classification (According their structures)： 1.Beta-Lactam antibiotics (β –内酰胺类) 2.Tetracylines antibiotics (四环素类) 3.Aminoglycoside antibiotics (氨基糖甙类) 4.Macrolides antibiotics (大环内酯类) 5. Others

Classification(According to their mechanism of actions 1. Inhibit the biosynthesis of bacterial cell walls(b-lactam) 2. React with cell membrances(polymycin) 3. Disturber with the biosynthesis of protein(aminoglycosides) Inhibit the replication and transcription of nucleonic acid (Nalicixic acid)

Classification (According to their mechanism of actions 1. Inhibit the biosynthesis of bacterial cell walls (β –Lactam) 2. React with cell membrances (Polymycin) 3. Disturber with the biosynthesis of protein (Aminoglycosides) 4. Inhibit the replication and transcription of nucleonic acid (Nalicixic acid)

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1. B-Lactam Antibiotics * The group of antibiotics known as the B-lactams include penicillins, cephalosporins, monobactams and the carbapenems N N C-R CO COH Penicillin nucleus Cephalosporin nucleus HO R N 5C-Q-% 5-R SO.H COH Monobactam nucleus Carbapenem nucleus

1.*β –Lactam Antibiotics *The group of antibiotics known as the β-lactams include penicillins, cephalosporins, monobactams and the carbapenems

These all share a common B-lactam ring. The ring is very strained and the bond between the carbonyl and the nitrogen in the p-lactam ring is very labile and hence makes the molecule reactive. The r-group substitute of the penicillin nucleus can be changed to give the molecule different antibacterial properties. The two naturally occurring penicillins from Penicillium notatum are enicillin G,[Benzyl penicillin,R=CH] and Penicillin V, PHenoxymethyl penicillin,R=CH,O(C6H6)1 X H R NH H COOH

These all share a common β-lactam ring. The ring is very strained and the bond between the carbonyl and the nitrogen in the β-lactam ring is very labile and hence makes the molecule reactive. The R-group substitute of the penicillin nucleus can be changed to give the molecule different antibacterial properties. The two naturally occurring penicillins from Penicillium notatum are Penicillin G, [Benzyl penicillin, R = C6H6 ] and Penicillin V, [Phenoxymethyl penicillin, R = CH2O(C6H6 )] N S O H COOH X H R NH O

The B-lactam structure is derived from two covalently bonded amino acid residues; cysteine and valine. This forms via a tripeptide intermediate where the third amino acid is replaced by the variable r-group SH H2N HN HN OH Cysteine β- actam structure Valine

The β-lactam structure is derived from two covalently bonded amino acid residues; cysteine and valine. This forms via a tripeptide intermediate where the third amino acid is replaced by the variable R-group

Mechanism ofaction N D-Alanyl-D-Alanin Penicillins NAC NAi NAI NAD(NAM(AD

Mechanism of Action O R N N O O O O O O R N N O S D-Alanyl-D-Alanin Penicillins

The peptidoglycan cell wall is a branched polymer made of alternating NAG邗D-N- acetylglucosamine,乙酰葡糖胺]and NAMIβ-D-N- acetylmuramic acid,乙酰壁氨酸] residues Polypeptide chains are attached to the nam residues and these vary depending on the strain of bacteria. The mechanism for cross-linkage is shown below. It is the terminal D-alanyl-D alanine residues of the polypeptide chain off of the nam residues that binds to the transpeptidase which cross-links that chain with the adjacent peptidoglycan strand. Penicillin binds at the active site of the transpeptidase enzyme that cross-links the peptidoglycan strands. It does this by mimicking the D-alanyl-D-alanine residues that would normally bind to this site

The peptidoglycan cell wall is a branched polymer made of alternating NAG [β-D-N-acetylglycosamine,乙酰葡糖胺] and NAM [β-D-N-acetylmuramic acid，乙酰壁氨酸] residues. Polypeptide chains are attached to the NAM residues and these vary depending on the strain of bacteria. The mechanism for cross-linkage is shown below. It is the terminal D-alanyl-D￾alanine residues of the polypeptide chain off of the NAM residues that binds to the transpeptidase which cross-links that chain with the adjacent peptidoglycan strand. Penicillin binds at the active site of the transpeptidase enzyme that cross-links the peptidoglycan strands. It does this by mimicking the D-alanyl-D-alanine residues that would normally bind to this site

Peptidoglycan Cell Membrane