6. • Nhoùm amin vaø guanidin aminosid coù tính base
(pka 7,5-8), thöôøng ñöôïc söû duïng ôû daïng muoái.
• Daïng muoái: thöôøng laø muoái sulfat, haùo aåm, raát tan
trong nöôùc, khoâng tan trong alcol vaø dm höõu cô.
• Dung dòch ôû pH trung tính beàn vôùi nhieät, thuûy giaûi
chaäm trong moâi tröôøng acid.
TÍNH CHAÁT LYÙ HOÙA
Kanamycin A, R=OH
Kanamycin B, R=NH2
Muốn có tác dụng toàn thân
phải sử dụng bằng đường tiêm
* Nhoùm NH2 vaø OH
8. IDENTIFICATION
First identification C, D.
Second identification A, B, D.
A. Dissolve about 10 mg in 1 ml of water R and add 5 ml of a 400 g/l
solution of sulphuric acid R. Heat on a water-bath for 100 min, cool and
dilute to 25 ml with water R. Examined between 240 nm and 330 nm
(2.2.25), the solution shows no absorption maximum.
B. Thin-layer chromatography (2.2.27).
………………………………………………………..
DetectionıSpray with ninhydrin solution R1 and heat at 110 °C for 5 min.
C. Examine the chromatograms obtained in the test for composition.
ResultsıThe chromatogram obtained with the test solution shows 5
principal peaks having the same retention times as the 5 principal peaks
in the chromatogram obtained with reference solution (a).
D. It gives reaction (a) of sulphates (2.3.1).
Gentamicin Sulphate
21. Gentamicin C-2a + N
ROCHN
O CO2H
betalactam (active)
NH2
O
sugar
O
sugar
HO
HN
O
NH
CO2H
ROCHN
(active)
(inactive)
22. • Ñoät bieán treân ribosome
– Söï ñoät bieán xaûy ra taïi nôi keát hôïp vôùi thuoác
• Giaûm tính thaám KS qua maøng vi khuaån
– Thuoác khoâng vaøo ñöôïc beân trong, khoâng theå töông taùc vôùi
ribosome
• Enzymes thoaùi hoùa aminoglycosides
– Aminoglycosides coù theå bò baát hoaït bôõi phosphorylation,
acetylation, or adenylation
Baét nguoàn töø 1 trong 3 cô cheá sau:
1- Drugs. 2001. 61(6): 713-721
2- Current Drug Targets – Infectious Disorders. 2002, 2: 143-1604
Kanamycin A, R=OH
Kanamycin B, R=NH2
Sự đề kháng
23. - AAC: aminoglycoside acetylase
- APH: aminoglycoside phosphorylase
- ANT: aminoglycoside nucleotide transferase
O
NH2
O
HO
X
Y
O
O
H2N
HO
HO
H
H2N
HO NHR
OH
Ac
Ad Ac
Ac
Phos
Ad
Ac
Tobramycin (X=H, Y=NH2, R=H)
Kanamycin A (X=OH, Y=OH, R=H)
Amikacin (X=Y=OH, R=COCHOHCH2CH2NH2)
(Ad: adenylation; Ac: acetylation;
Phos: phosphorylation)
Giải quyết vấn
đề đề kháng?
27. • Phaûn öùng do nhoùm streptidin:
- phản ứng Sakaguchi (phát hiện guanidin)
Dạng muối bền /dd nước ở pH= 3-7
C. Dissolve 0.1 g in 2 ml of water R , add 1 ml of α-naphthol
solution R and 2 ml of a mixture of equal volumes of strong
sodium hypochlorite solution R and water R. A red colour develops
BP 2007
Streptomycin
28. • Phaûn öùng do nhoùm streptoza:
– Phaûn öùng vôùi kieàm, streptoza chuyeån thaønh maltol,
chaát naày taïo phöùc maøu tím beàn vôùi Fe3+.
Dạng muối bền /dd nước ở pH= 3-7
Streptomycin
29. Ñònh löôïng: ño quang, pp vi sinh vaät
O
R1
O
H
OR2
H
OH
CHO
CH3
H
OH
O OH
O
R1
O
H OR2
H
CH3
H
O OH
R1
O
H OR2
H
H3C OH
- R2
OH
O OH
R1
O
H
O
R1
O
H
H3C OH
H
H3C OH
O
H
H
- R1
OH O O
H3C OH
O O
H3C O Fe
3
38. AMINOSID COÙ GENIN DESOXY-2-STREPTAMIN
Gentamicin
Mixture of the sulphates of antimicrobial substances produced by
Micromonospora purpurea, the main components being gentamicins
C1, C1a, C2, C2a and C2b.
Hàm lượng của mỗi thành phần
được xác định bằng HPLC.
39. AMINOSID COÙ GENIN DESOXY-2-STREPTAMIN
Gentamicin
O
O
O
O CH3
HO
NH2
HO
H3C
NH2
H2N H2N
H3CHN OH
Ac
Ac Ac
Ad
Gentamicin C-2
Mixture of the sulphates of antimicrobial substances produced by
Micromonospora purpurea, the main components being gentamicins
C1, C1a, C2, C2a and C2b.
53. HO NH2
O
OH
N
O
H3C
O NH CH NH
H3C
O
NH2
CH3
H3C
Dactimicin
Astromicin
The in vitro activity of the new aminoglycoside dactimicin in
comparison to amikacin was tested alone and in combination with
piperacillin, mezlocillin and ceftazidime against freshly isolated clinical
pathogens. Dactimicin was more active than amikacin against
Enterobacter cloacae, Providencia rettgeri and Salmonella spp.
Eur J Clin Microbiol Infect Dis. 1989 Jul;8(7):639-43.
dactimicin: ít ñoäc vaø hieäu quaû treân maàm ñeà kháng các aminosid khác.
