沈阳药科大学：《药物化学》课程教学资源（PPT课件讲稿）抗生素 Antibiotics

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

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(-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 mechanismof 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) 4. 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)

分,为升胞浆膜细胞浆细胞壁孙制肥台成 肯素,头想茁素 (多粘酉 制 西素、忙褥素B 抑制DNA台成 喹诺类 蛋当历 影响叫酸代谢 (磺按类) 影啊蛋白蛋合成 愿婀RNA台成 (氨基甙员,环 (甲哌力复雄素) 累类、烈素 花素

1. B-Lactam Antibiotics The group of antibiotics known as the B-lactams include penicillins, cephalosporins, monobactams and the carbapenems N C-R COH COH Penicillin nucleus Cephalosporin nucleu HO N HC 5-R N 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 p-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=C6H6] and Penicillin V, PHenoxymethyl penicillin,R=CH,O(C6H6) X H R NH O 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 HoN HN HN OH Cysteine 阝 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 D-Alanyl-D-Alanin Penicillins NAG(NAM(NAG NAM

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 Iβ-D-N- acetylglucosamine,乙酰葡糖胺]and NAM IB-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 Dd-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