药物化学课件讲义ANTIBIOTICS

"One sometimes finds what one is not looking for."
Because of its cheapness, efficacy, and remarkable lack of toxicity (except for acutely allergic patients). Peniciline G remains a remarkably useful agent for treatment of disease caused by susceptible microorganisms. It is the drug of choice for more infections than any other antibiotics. “ Fist is best”
Penicillin X (青霉素 X)
R= HO
Fermentation Derivater of Penicillium
Penicillin K (青霉素 K)
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)]
In clinic the antibiotics are used to be antibacterial mainly,but, in recent year, they can also be used for anti-cancer,antiviral ,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.
青霉醛
R
NH
OO
S N H COOH
N R
S
O
N
Hale Waihona Puke O H COOHCOOH
S N
R
N
COOH
青霉二胺
青霉酸
Semi- Synthetic Penicillins
O
HH
R C NH
S
N
O
H COOH
Penicillin G (青霉素 G)
R=
Fermentation Derivater of Penicillium
(Nalicixic acid)
1.*β –Lactam Antibiotics
*The group of antibiotics known as the β-lactams include penicillins,
cephalosporins, monobactams and the carbapenems.
Penicillin G and V are only active against Gram Positive bacterial cells, which have an exposed layer of peptidoglycan around the outside of the cell wall, as shown above. Gram Negative bacteria have a more complicated composition, which Penicillin G and V can not destroy
The disadvantages of Fermentation-Derived Penicillins (Penicillin G)
1.Narrower in antibacterial spectrum, active for G-P only, poor active for G-N
2.Can not be oral administrated , just for injection.
Penicllin-binding poteins,PBPs
R
OH
O H
N COOH
PBPs NH3
Penicliins Nature Penicillin (Fermentation-Derived Penicillins)
Penicillin was discovered by Alexander Fleming in 1929.
3.allergic action
4.susceptible to acid and Penicillinase
5.produces Penicllins-resistant bacteria.
O R NH
O
S
pH=4
N
R.T
H COOH
CH3
NH2
C CH COOH
CH3 SH
青霉胺
RCONHCH2 CHO
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
O XH
R NH
S
N
O H COOH
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.
The labile β-lactam ring in penicillin reacts with a serine residue in the transpeptidase as shown below. This reaction is irreversible and so the growth of the bacterial cell wall is inhibited. The resulting complex is stable to water and remains attached to the polypeptide chain. The peptidoglycan transpeptidase is not needed in animals as their cells do not have cell walls. Therefore, the penicillin can safely disrupt the bacterial cell wall biosynthesis without harming existing cells in the body.
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
Fleming found that it was effective against many Gram positive bacteria in laboratory conditions, and he even used locally applied, crude preparations of this substance, from culture filtrates, to control eye infections. However, he could not purify this compound because of its instability, and it was not until the period of the Second World War (1939-1945) that two other British scientists, Florey and Chain, working in the USA, managed to produce the antibiotic on an industrial scale for widespread use. In recognition for his contribution, Alexander Fleming was knighted in 1944. With Chain and Florey he was awarded the Nobel Prize in 1945.