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KHANG SINH -LACTAMIN (-LACTAM)
Azetidin = -lactamin
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CAC THUOC CHNHPenicillin: (PENAM)
penicillin G; penicillin V
methicillin; oxacillinampicillin; amoxicillin;carbenicillin; ticarcillin
Cht c ch -lactamase: (OXAPENAM)acid clavulanic
CARBAPENEM: imipenem
N
S
O
N
O
O
NO
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CAC THUOC CHNHCephalosporin (CEPHEM)
Th h I : cephalexin; cephalothinTh h II: cefoxitin; cefaclorTh h III: cefotaxime; cefoperazone; ceftriaxone
Th h IV: cefepimeTh h V: ceftobiprole
MONOBACTAM: aztreonam
NO
S
NHO
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C CHE KHANG KHUAN
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C CHE KHANG KHUAN
Transpeptidases = Penicillin-binding proteins (PBP)
= Protine de liaison aux pnicillines (PLP)
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Drugs that inhibit the cross-linking of the peptidoglycan chains The final step in the
formation of the cell wall is the completion of the cross-links. This converts the water-soluble and therefore
mobile peptidoglycans into the insoluble stationary cell wall. Investigations using Staphylcoccus aureus
indicated that the cross-linking is brought about by a multistep displacement of the terminal alanine of the
peptide attached to one peptidoglycan chain and its replacement by the terminal glycine of the peptide
attached to a second peptidoglycan chain (Fig. 7.26). This reaction is catalysed by transpeptidases.
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C CHE E KHANG
Vi khuan e khang lactamin theo cac c che sau:e khang enzym: VK sn xut -lactamase
e khang khong enzym:- thay oi tnh tham thau cua mang te bao- bien mat hoac bien oi cac PBP
- Efflux pumps Vd: multidrug resistance (MDR) pumps
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Th d: S khng ca Staphylococcus aureus
- Sx penicillinases
- Thay i PBP: PBP 2a tm thy trong MRSA (Methicillin-resistant Staphylococcus aureus)
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(A) Stereo view of the active site of
PBP 2a ofS. aureusdepicted as a
solvent-accessible surface (green).
The side chains of the active-site
serine and lysine are shown as
capped sticks and colored by atomtypes (carbon in gray, oxygen in
red, and nitrogen in blue). The
backbone of the loop that caps the
active site is shown as an orange
wire.
(B) Stereo view of the active site
from the same perspective shown
in panel A, except the loop is now
shown as a solvent-accessible
surface for both the backbone and
the side chain functionalities. The
presence of the loop blocks the
active-site access for molecules
the size of typicallactamantibiotics.
The development of newlactam antibiotics that inhibit PBP 2a is significant progress andoffers a glimmer of hope for the future treatment of MRSA infections, including those caused by
vancomycin-resistant and -intermediate strains.
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HOAT TNH KHANG KHUAN
Quan he cau truc tac ong
N
O
COOHH
HN
O
O
RH H
12
3
4
56
7
Penicillin
N
NH
O
O
R1H H
1
3
4
5
67
S
COOH
R2
N
NH
O
O
RH R1
SO3H
R2
cephalosporin
monobactam
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NHOM PENICILLIN
Benzyl penicillin = Penicillin G
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N
S
COOHH
HN
O
O
R
H H
12
3
4
5
6
7
Penicillin
N
S
COOHH
H2N
O
H H
12
3
4
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7
6-aminopenicillinic acid
Danh phap IUPAC
Amid- 6 cua acid (2S, 5R, 6R-amino-6-dimethyl-3,3-oxo-7-thia-4-aza-1-bicyclo [3.2.0]-heptan carboxylic).
Danh phap thong dung
Penicillin nh la nhng amid cua acid 6-amino penicillanic (6- APA).
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IEU CHE
T nam Penicillium notatum.
Penicillin G (them vao moi trng acid phenylacetic )
Penicillin V (them vao moi trng acid phenoxyacetic )
60mg/L 20 g/L
Phng phap sinh hoc
N
S
O
HN
CH3
COO
HH
H
CH3
COCH2
R'
N
SNH
H COO
H H
O
C
OH2CO
R
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IEU CHEBan tong hp
N
S
COOHH
HN
O
O
R
H H
12
3
4
56
7
Penicillin
N
S
COOHH
H2N
O
H H
12
3
4
56
7
6-aminopenicillinic acid
B-condition = 1. Me2SiCl2 2. n-Bu-OH, -40oC 3. H2O, 0
oC
A- condition
B-condition
A-condition = Aclylase
N
S
COOHH
HN
O
O
R1
H H
12
3
4
56
7
Penicillin
N
S
COOHH
H2N
O
H H
12
3
4
56
7
6-aminopenicillinic acid
R'COCl, Et3N
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BAN TONG HPAMOXICILLIN
N
S
OCOOH
CH3
CH3H2N
6-APA
+ SiCl
CH3
CH3
CH3
trimethylclorosilon
N
S
OCH3
CH3H2N
OO Si
H3C
CH3
CH3
6-aminopenicillanic acidtrimethylsilyl ester
(I)
(I) +
HO
Cl
O
NH2
.HCl
D-(-)2-(4-hydroxyphenyl)-glycylclorid. hydroclorid
N,N-dimethylanilin N
S
OCH3
CH3HN
OO Si
H3C
CH3
CH3
O
NH2
HO
amoxiillin trimethylsilyl ester(II)
(II)H2O, pH 1,3-1,5
N
S
OCOOH
CH3
CH3HN
O
NH2
HO
Amoxcicillin
R
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Tnh chat vat ly
Cac penicillin di dang muoi hoac dang acid la nhng bot trangkhong mui khi tinh khiet.
Pho UV
N
S
COOHH
HN
O
O
R
H H
12
3
4
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Penicillin
Benzylpenicillin K
(BP 2007)
Absorbance (2.2.25)
Dissolve 94.0 mg in water R and dilute to 50.0 ml with the same solvent.
Measure the absorbance of the solution at 325 nm, 280 nm and at themaximum at 264 nm, diluting the solution, if necessary, for the
measurement at 264 nm. The absorb ances at 325 nm and 280 nm d o
no t exceed 0.10 and th at at the maxim um at 264 nm is 0.80 to 0.88,
calculated on the basis of the undiluted (1.88 g/l) solution. Verify the
resolution of the apparatus (2.2.25); the ratio of the absorbances is at
least 1.7.
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Tnh chat vat ly
Pho IR: vung 1600-1800 cm-11760 va 1730 cm-11700 va 1650 cm-11600 cm-1
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Tnh chat vat ly
Nng sut quay cc
Specific optical rotation (2.2.7)
Dissolve 0.500 g in carbon dioxide-free water R and dilute to 25.0 ml with the
same solvent. The specific optical rotation is + 270 to + 300, calculated with
reference to the dried substance.
Benzylpenicillin K (BP 2007)
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Tnh acid Tao muoi natri va kali (bn)
Tan trong nc, pha tiem
Tnh chat hoa hoc
N
S
COOHH
HN
O
O
R
H H
12
3
4
5
6
7
Penicillin
Natri amoxicillinK Benzylpenicillin
R
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Tnh acid Tao muoi vi cac amin:
Procain penicillin: tac ong keo dai 24-48 h,
Benethamin penicillin: tac ong keo dai 3-7 ngay,
Benzathin penicillin: tac ong keo dai 2-4 tuan.
Tnh chat hoa hoc
N
S
COOH
H
HN
O
O
H H
12
3
4
56
7
Penicillin
Procain benzylpenicillin
Benzathin benzylpenicillin
R
H H
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Tnh acid
Tao thanh nhng este, tien chat cua PNC co kha nang phong thchtr lai cac khang sinh nay in vivo.
Tnh chat hoa hoc
HN
O
H2
N H
N
S
OCOOR
CH3
CH3
R = O CMe3
O
Pivampicillin
R = O
O
Talampicillin
R =O
Me
O Me
O
Bacampicillin
Tin dc ampicillin gip hp thu KS tt hn qua rut
N
S
COOHH
HN
O
O
H H
12
3
4
56
7
Penicillin
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Penicillin
O
O O OMe3
O
Esterase
H
Penicillin
O
O OH
H
Penicillin
O
OH+ CH2O
C ch thy phn acyloxymethyl ester bi esterase
T h kh b b t l t
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C NR2
O
R
: :
..
C
R
O..: :
NR
R
Comparison of tertiary amide and -lactam carbonyl groups
Tnh khong ben cua vong beta lactam
T h kh b b t l t
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Tnh khong ben cua vong beta lactam(OH- hay penicillinase)
- Chu y tng k vinhng chat co tnh kiem
penicillin
OH
N
S
O
HHNR
O
H
CO2H
HN
S
COOH
C
O
HO
H HR
O
acid penicilloic
S
N COOHROCHN
OHO
- CO2
S
NH
COOHROCHNS
NH
ROCHN CO2H
acid penilloic
ROCHNO
H
penilloaldehyd
HS
COOHH2N+
D-penicillamin
-Phn ng d ng
-nh lng
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S alcol phan va amino phan
N
S
O
NH
CH3
COOH
H
CH3
CR
O
N
S
CO
NH
CH3
COOH
H
CH3CR
O
DD
Tac nhan ai nhan san pham
alcol R'OH R'O ester penicilloic
amin R'-NH-R'' R'-N-R'' amid penicilloic
hydroxylamin NH2OH NH-OH d/c a. hydroxamic
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HN
S
CH3
CH3
COOH
HNCR
O
O NH
OH
N
S
CH3
CH3
COOH
HNCR
O
O
NH2OH
HN
S
CH3
CH3
CO
HNCR
O
ONH
O
Cu2+
Cu O
(xanh ngoc)
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S m vng -lactam c xc tc bi cc ion kim lai(Phc to thnh vi ion kim lai hat ha s tn cng i nhn)
N
S
CH3
CH3
OO
O M
2 +
HNAc
N
OO
O M
2 +
HNAc
H H H HS
X
Ch : vng -lactam b m, KS mt tc dng
T h kh b b t l t
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Tnh khong ben cua vong beta lactam(acid mnh, nng hoc HgCl2)
N
S
O
N H H
CH2O2H
R
O
H
H
HN
SN H H
CO2H
R
O
H
O
N
HSN H
CO2H
R
O
O
HN
HSN
CO2H
R
O
O
HN
S
HN
CO2H
R
O
OHO
H H
acid penicilloic
ROCHNO
H
penilloaldehyd
HS
COOHH2N+
D-penicillamin
S
N
H
ROCHN CO2H
acid penilloic
Peni G bn pH= 6-7.Hat tnh KS gim rt nhanh
pH
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X = NH2, Cl, PhOCONH, heterocyles
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N
S
H
CO NH
COO
C
H
NH2
O
H H
Na
Ampicillin
Na
N
S
H
CO NH
COO
C
H
NH2
O
H HHO
Amoxicillin
N
S
O
HN
CH3
COO
HH
H
CH3
COCH2
R'
N
SNH
H COO
H H
O
C
OH2CO
R
Peni G Peni V
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Kiem nghiem
nh tnh:
- Pho IR- Sac ky lp mong
- Phan ng vi hydroxylamin, sau o vi CuSO4
- Phan ng mau vi acid H2SO4
- Phan ng mau vi dd formaldehyd trong H2SO4
N
S
O
HN
CH3
COO
HH
H
CH3COCH2
R'
Kiem nghiem
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Kiem nghiem
Kiem tinh khiet
- hp thu UV
- pH
- Nang suat quay cc
- Cac tap chat thong thng: Th du kim loai nang
- Cac tap chat lien quan: Th du N,N-dimethylanilin (trongampicillin hoac amoxicillin) bang sac ky kh.
N
S
H
CO NH
COO
C
H
NH2
O
H H
Na
Ampicillin
Na
N
S
H
CO NH
COO
C
H
NH2
O
H H
HO
Amoxicillin
Kiem nghiem
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Kiem nghiem
nh lng
1. PHNG PHAP OXY HOA KH
2. PHNG PHAP HPLC
3. PHNG PHAP VI SINH VAT
(Xac nh hoat lc cua khang sinh)
Penicilinphan huy
D-penicillamin + acid penaldic
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Cac khang sinh nhom penicillin rat t oc,
Tai bien chu yeu do d ng,
D ng nhe gay nga, noi me ay D ng nang gay shock phan ve
OC TNH VA TAI BIEN
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PENICILLIN NHOM IPenicillin thien nhien
Penicillin G (benzyl penicillin)Dang tac dung nhanh: Na/K benzyl penicillin
Dang tac dung cham: procain PNC, benethamin PNC, benzathin PNC
Penicillin V (phenoxy methyl penicillin)
N
S
O
HN
CH3
COO
HH
H
CH3COCH2
R'
N
SNH
H COO
H H
O
C
OH2CO
R
Peni G Peni V
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Ben trong moi trng acid,hap thu tot hn, hoat chattrong huyet thanh cao hn,T1/2 dai hn.
T PNC-G: azidocillin,clometocillin
T PNC-V: pheneticillin,propicillin, phenbenicillin
PENICILLIN NHOM IPenicillin ban tong hp
X
X
CH
Z
CO HN
N
S
O
H H
CH3
CH2
COOH
Z = N3- ; X = H : azidocillin
Z = OCH3- ; X = Cl : clometocillin
O CH
Z
COHN
N
S
O
H H
CH3
CH2COOH
Z = CH3- : pheneticillin
Z = C2H5- : propicillinZ = C6H5- : phenbennicillin
PENICILLIN NHOM I
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Pho khang khuan hep, chu yeu tren gram (+):
Cau khuan gram (+): tu cau khong tietpenicillinase, lien cau, phe cau
Cau khuan gram (-): lau cau (khuynh hng tang
MIC va xuat hien nhng chung e khang). Xoan khuan: xoan khuan giang mai, leptospira
va Borelia burgdorferi.
Trc khuan gram (+): trc khuan gay benh bach
hau, benh than, listeria(viem mang nao),erysipelothrix (viem quang).
PENICILLIN NHOM IPho khang khuan
KHONG TAC DUNG TREN TRC KHUAN GRAM (-)
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PENICILLIN NHOM IIMeticillin, oxacillin, cloxacillin, dicloxacillin,
Pho hep gan giong penicillin nhom I, nhng co kha nangkhang lai penicillinase do S. aureustiet ra.
N
S
O
HN
CH3
COO
HH
H
CH3CO
O CH3
O CH3
NaMeticillin
PENICILLIN NHOM II
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N
S
O
HN
CH3
COO
HH
H
CH3COCC
N
O
C CH3
X
Y
Naisoxazolylpenicillin
PENICILLIN NHOM IIMeticillin, oxacillin, cloxacillin, dicloxacillin,
X Y
-------------------------------------------------------------
Oxacillin (Bristopen) H HCloxacillin (Orbenin) Cl H
Dicloxacillin (Dicloxil) Cl Cl
Fluocloxacillin (Floxapen) Cl F
Chu y: s a thay the lam giam hoat tnh khang sinh
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Ph KK ca mt penicillin ph thuc vo:- Cu trc- Kh nng xuyn mng VK gram m-Tnh nhy cm vi betalactamse
-i lc vi enzym mc tiu transpeptidase- Tc b bm ra ngai VK gram m
M mm (trial and error) tm kimpenicillin ph rng
Mt lng ln cht tng ng c tng hp vi nhng thay i nhnh bn, vi nhng nhn xt SAR nh sau:- Nhm hydrophobic (peni G) tt trn gram + nhng khng tt trn gram _- S gia tng trn gram m tm thy tt nht vi nhng nhm hydrophylic carbon alpha (iu ny c cho l tr gip nhng penicillin ny bngqua porin outercell membrane ca VK gram m)
N
S
O
HN
CH3
COO
HH
H
CH3COCH2
R'
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N
S
O
HN
CH3
COO
HH
H
CH3COCH2
R'
The tren C cua chc carboxamid (PNC- G):
amin, hydroxyl, carboxylic, sulfonilic
M rong hoat pho sang vi khuan gram am
PENICILLIN NHOM III
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PENICILLIN NHOM III
S
O
NH
COOH
C
ONH
2
HOOC
penicillin N
Dch nuoi cayCephalosporium acremonium
(yeu hn peni G tren gramdng,
nhng co tac ong tren gram am)
PENICILLIN NHOM Ampicillin
1945
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Nhom III: gom co 2 phan nhom IIIA va III B:
III-A: khong co nhom the tren amin (NH2):
Ampicillin, Amoxicillin
III-B: co nhom the tren amin (NH2):
Azlocillin, Mezlocillin, Piperacillin
PNC NHOM III-A Ampicillin, Amoxicillin
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PNC NHOM III-A Ampicillin, Amoxicillin
2S,5R,6R)-6-[[(2R)-2-amino-2-phenylacetyl]amino]-3, 3-dimethyl-7-oxo-
4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
(2S,5R,6R)-6-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-
dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid,
- Bn vi acid- Nhng nhy cm vi lactamse.- Hp thu km qua rut
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Pho cua penicillin G cong them mot so vi khuangram am nh Haemophilus, Escherichia, Proteusmirabilis, Salmonella, Shigella.
Mot so vi khuan gay nhiem trung mac phai tai benhvien khong nhay cam vi nhom khang sinh nay:Enterobacter, Serratia, Proteus indol dng,Providencia, Bacillus pyocyanic.
Pho khang khuan III-AAmpicillin, Amoxicillin
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PNC NHOM III-BAzlocillin, Mezlocillin, Piperacillin
Tac ong tren cac mam e khang vi ampicillin nh:Klebsiella, Enterobacter, Serratia, Pseudomonas
Piperacilin phoi hp vi aminosid hoac vi chat c chebetalactamase
PENICILLIN NHOM IV (-carboxy-PNC)
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Na
N
S
H
HN
COOO
H HCOC
H
COO
Ar
Z
S
Z
Na
Na
Ar
Carbenicillin
Carindacillin
Ticarcillin
PENICILLIN NHOM IV (-carboxy-PNC)Carbenicillin, ticarcillin, carindacillin
Z=phenyl : Carfecillin
N
SHNH H
O
OC
HC
SO3H
COO Na
Sulbenicillin
Ben ve mat hoa hoc
Hoat tnh KK tng t cac
-carboxy-PNC
- Hoat tnh tren trc khuan mu xanh- ong van vi aminosid- Ticarcillin hoat tnh 2 lan manh
hn carbenicillin.
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PENICILLIN NHOM VI (Amidino-PNC)
N
S
O
N
CH3
COO
HH
H
CH3CHN
R' Ten hoa hoc
Na+
CH2 O CO C(CH3)3(HCl)
Mecillinam
Pivmecillinam(Selexid)
Amidinopenicillin R'
Pho KK hep, tap trung chu yeu tren VK gram am.
Rat nhay cam: Escherichia coli.
Nhay cam: Yersinia, Salmonella, Shigella, Enterobacter, Citrobacter,
Klebsiella (khong san xuat hoac san xuat yeu penicillinase).
Khong e khang cheo vi ampicillin
N
azepan-1-ylmethanimine
CH NH
(nhn azepin gn trn lin kt amidine)
CHAT C CHE LACTAMASE
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CHAT C CHE -LACTAMASE
AI CNG
Nhieu loai vi khuan co kha nang tiet ra cac enzym betalactamase phan huy cac khang sinh ho beta lactamine.
S san sinh cac enzym nay co the la t nhien hay tiepnhan c. Men beta lactamase bao gom penicilinase va
cephalosporinase.
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Chat c che beta lactamase + cac penicillin: m rongpho khang khuan cua nhng chat nay len cac vikhuan tiet men penicillinase.
Sau khi gan vi men penicillinase, cac chat nay se bphan huy.
C CHE TAC ONG
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Acid clavuclanic (suicide inhibitor)
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Acid clavuclanic (suicide inhibitor)
Thu c t Streptomyces clavuligerusCau truc clavam (oxapenam)
c s dung dang muoi kali clavuclanat
Cac phoi hp: acid clavuclanic amoxicillin,
acid clavuclanic ticarcilinclavulanate meropenem (ang nghin cu)
NO C
HH
H
O
CH2OH
HH COOH
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Cai thien tren nhng mam nhay cam san xuat betalactamase nh Neiserria gonorhoeae, Haemophilus,E. coli, Salmonella.
A. clavuclanic ticarcillin
Phoi hp nay gia tang tac ong tren Staphylococcus(95% Streptococcus nhay cam vi phoi hp acidclavuclanic ticarcillin so vi 49% neu ch s dungmot mnh ticarcillin).
Pho khang khuan cua phoi hpB. clavuclanic amoxicillin
Sulbactam
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Dan chat cua penam, ban tong hp t 6 APA
Cau truc tng t penicillin nhng khong co nhom the C6 (mat C*),
S v tr 4 c oxy hoa thanh SO2, Cau hnh C2 va C5 giong penicillin
Sulbactam(2S,5R)-3,3-Dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic
acid 4,4-dioxide
Phoi hp sulbactam-ampicillin
N
SHH
H
O H COOH
CH3
CH3
O O
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- Dan chat este i t sulbactam va ampicillin
- Hoat tnh tren cau khuan gram dng, gram am; trckhuan gram dng, gram am
- c dung trong tai-mui-hong, ho hap, sinh duc, datren nhng mam nhay cam
Sultamicillin
N
S
CH3
CH3
O
OO
O
N
S
O
H3C
H3C
OO
O
H
N
O
NH2
Sultamicillin
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Dan chat cua sulbactam ma mot nhom methyl mangnhom the triazolyl
Chat c che betalactamase khong thuan nghch phorong
S dung di dang phoi hp tazobactam - piperacillin
Tazobactam
N
SHH
H
O H COOH
CH2
CH3
O O
NNN
CARBAPENEM
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NO
Carbapenem
N
HO
H3C
OCOOH
S
NH2
Thienamycin (1977)
Thienamycin :
- trch t moi trng nuoi cay Streptomyces cattleya.- hoat tnh khang khuan rong- hoat tnh tren Pseudomonas
- khang lai -lactamase
SNH2
SNH CH NH
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NO
CO2
S
R
Me
OHHH
Plays a role in
lactamase resistance
Double bond leading tohigh ring strain and increase
in lactam reactivityThienamycin R = NH3
Imipenem R = NH-CH=NH
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IMIPENEM
Acid [hydroxy-1 ethyl (R) ]6[[(iminomethylamino-2)ethyl]thio]-3-oxo-7-aza-1bicyclo [3.2.0]hepten-2
carboxylic-2 (5R,6S).
N
HO
H3C
OCOOH
S
NH2
Thienamycin (1977)
N
HO
H3C
OCOOH
S
NHNH
Imipenem
benzyl formimidat
IMIPENEM
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Pho khang khuan
Ben vng vi men beta lactamase, pho khang khuan rat rong, bao gom:
-Cau khuan gram dng: Staphylococcus nhay meticillin (Staphylococcus khangmeticillin e khang vi imipenem), Strepococcus (ke ca nhom D),Pneumococcus, Enterococcus.
-Cau khuan gram am: Neisseria
-Trc khuan gram dng: Clostridium, Listeria monocytogenes
- Trc khuan gram am: H. influenzae, E. coli, Klebsiella, Proteus mirabilis,Enterobacter, Citrobacter, Serratia, Proteus vulgaris, Bacteroides fragilis,Acinetobacter, P. aeruginosae.
N
HO
H3C
OCOOH
S
NH
NH
IMIPENEM
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- IV cham.
- De b phan huy bi dehydropeptidase ong than khi s dung thng
ket hp imipenem vi cilastin (chat c che enzym dehydropeptidase) e gii
han s chuyen hoa nay.
cilastin
N
HO
H3C
OCOOH
S
NH
NH
4-Methyl carbapenem
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N
HO
OCO2H
S
HN
NH
Imipenem
Bn hn i vi s thy gii ca dehydropeptidase
NO
CO2
S
Me
OHHH CH3
HN
C
O
N
R2
R1
Meropenem R1= R2 = Me
Ertapenem R1= H; R2 =
CO2
Ni chung, carbapenem c ph khng khun rngnht trong tt c cc KS lactames.
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ME1036. ME1036 (CP5609; developed by Meiji Seika, licensed
by Forest) is a broad-spectrum carbapenem that binds
with a high affinity to PBP 2a of MRSA (IC50 0.13 to 0.73
g/ml) and that exhibits potent in vitro inhibitory
activity against MRSA .
A series of 4-methyl carbapenems having structural similarityto ME1036 showed potent activities against MRSA and PRSP, as
well as against the gram-negative organism ampicillin-resistant,
-lactamase-negative Haemophilus influenzae
N
HO
OCO2H
S
HN
NH
Imipenem
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PZ-601 (Razupenem). PZ-601 (formerly known as SMP-
601; licensed from Dainippon Sumitomo Pharma Co., Ltd.,
Osaka, Japan) is a new carbapenem currently being developed
by Protez Pharmaceuticals (now Novartis) that has
demonstrated a high degree of potency against MRSA.
N
HO
OCO2H
S
HN
NH
Imipenem