Cc dn xut c cha cc nhn c bn:

c phn thnh hai nhm hai th h da trn tc dng v c

im cu to:
Quinolon th h I: C tc dng trn vi khun Gr (-): Ph tc dng hp, bt
u c nghin cu t ~ 1960. Cu to c cha nhm acid
Quinolon th h II: c tc dng trn c vi khun Gr (-) v Gr (+) v c im
cu to c cha nguyn t F (flo). Cn gi l flouroquinolone: Ph tc dng
rng, c nghin cu t nhng nm 1985. C kh nng hp th nhanh qua
c quan tiu ha, nn c th dng ung, ph bin rng trong cc c quan,
vi nng duy tr cao nn s dng tt trong thc t iu tr
Dn xut nalidixic c ph tc dng hp, hp th km yu cu phi tng hp cc dn xut mi.
Nguyn t N ti v tr s 8 c thay th bi C
Ti v tr s 6 v 7 ngng t vi h vng c nguyn t O lin hp
Dn xut khc ca nalidixic khi c gn nguyn t F vo nhn
c s gp phn m rng ph tc dng v y thc s l mt
tng thnh cng, bi cc thuc khng sinh quinolon hin nay,
u c cha nguyn t Flour.
Kt hp cc s thay i trn cho chng ta sn phm c tc dng khng khun hiu qu, thi gian
bn thi di v cc u im khc. M ra thi k pht trin mi cc thuc khng sinh h quinolon.
Nhm th F, piperazinyl

Thay N=C
Cc quinolon c tc dng c ch enzym ADN-gyrase v topoisomerase IV hai enzym c cai tr
quan trng trong qu trnh tng hp ADN ca vi khun, c th nh sau:
-Quinolon khng cha F (th h 1) ch tc dng ln AND-gyrase nn ph tc dng hp
-Quinolon cha F c ch c enzym topoisomerase IV, nn ph tc dng rng hn, v kh
nng khng thuc ca vi khun cng km hn, do kh nng t bin hai ln trn c hai
enzym thp hn
Vng lin kt enzym
mu
Vng lin kt AND mu xanh
Vng lin kt gia
cc phn t quinolon mu tm
Nghin cu v bin i cu trc ca cc dn xut khng sinh quinolon, rt ra cc c im cu
to nh sau:
C cha nhm carbonyl v tr s 4 v carboxyl v tr s 3 nhm c hot tnh khng khun
Vng dihydropyridon phi ngng t vi nhn thm (benzen hoc pyridine)
Nguyn t C ti cc v tr C2, C5, C6 c th c thay th bng nguyn t N
Nhm th ti N1 c th l cc dn xut alkyl hoc cycloalkyl hay aryl
Khng c nhm th ti v tr C2, cc nhm th ti v tr C5 (R1) v C6 (R2) v ti R3 c tc dng
tng mnh hot tnh:
R1 = F, hot tnh tng rt mnh v y l bc t ph trong nghin cu ng dng quinolon.
R2 = piperazyl, pyrrolidinyl m rng ph tc dng.
C th to vng lin kt cc v tr = 1 v 8; 6 v 7; 5 v 6.
Mc tiu: tng cng tc dng ln vi khun Gr (-); m rng ph tc dng sang Gr
(+); ph tc dng vi c cc vi khun k kh v khng in hnh, gim kh nng khng
thuc ca vi khun.
c im khng thuc ca vi khun:
- Vi khun thay i cu trc ca mng t bo, lm gim s thm nhp ca quinolon
qua mng t bo
-Vi khun hot ha bm ngc, y quinolon ra khi t bo
-Vi khun t bin c hai enzym AND-gyrase v topoisomerase
Ha dc cn tp trung n:
- Tng tnh thm thu ca thuc vo m v qua mng t bo
- Tng hot tnh ca thuc, m rng ph tc dng.
- Gim liu lng tc dng
- Tch cc ng phn hot quang nghin cu tm ra cc ng phn hot quang
c tc dng mnh.
- Ko di thi gian bn thi.
- Gim tc dng phu v c tnh, cc quinolon c nhiu tc dng phu do hot ph
rng v hot lc mnh
Tng hp ciprofloxacin
Aminosid l cc hp cht thin nhin thng c cu to gm mt
nhm genin vi nhiu nhm chc ng c nhm th amin. Do cc
hp cht ny cn c gi l nhm aminoglycosid. V d:

-c ch qu trnh sinh tng hp ca protein ca vi khun trong qu trnh nhn i AND, gy
sai lch trong qu trnh sao m ARN, dn n tng hp cc protein khuyt tt.

- Nhm chc amin l cn thit, gi vai tr tng tc vi th th . Cc nhm hydroxyl c tc
dng cho s thm nhp qua mng t bo vi khun.
- Khng thuc: Nh mi thuc khng sinh khc, vi khun cng c kh nng khng thuc
aminosid.
Hn ch khng sinh gn vo th th ca t bo vi khun ribosom: Cc nhm chc
b phong ta, di tc ng ca cc enzym.
Kh thm nhp qua mng t bo ca vi khun.
Vi khun t bin ti th th - ribosom.
- Hin nay, bng phng php bn tng hp
thu c nhiu aminosid c c im cu to
bn vng hn,
-Khng sinh c dng thn trng hn vi ch
nh v liu lng r rng.
Chloramphenicol c pht hin nm 1947 c hot ph rng, tc dng ln vi
khun Gr (+), Gr (-).
Cu trc gm c 3 phn
Nhn thm c nhm nitro v tr para
Mt chui 2-aminopropandiol-1,3
Mt nhm dichloracetyl

Bin i cu trc ti vng thm: hot tnh ch tn ti khi thay th bng nhm SO2CH3 ti v tr
para. Cc bin i khc lm gim hot tnh sinh hc (nhm th khc, thay nhn thm khc).
Bin i aminopropandiol: Hp cht chloramphenicol c 4 ng phn quang hc trong ch c
D (-)treo l c hot tnh, cn li l khng th hin hoc th hin cng thp. Nhm hydroxyl
phi trng thi t do di dng este ha ch c th l cc tin thuc
Bin i nhm dichloroacetyl: nhm acyl l cn thit cho kh nng th hin hot tnh. Th cc
dn xut khc vo v tr clo cho hiu qu khng cao