Effects of skeletal modifications of ciprofloxacin on ... - ResearchGate

JOURNAL <strong>of</strong> CHINESE CLINICAL MEDICINE VOLUME 2|NUMBER 4|April 2007
(61),56 (100).
1 唱Cyclopropyl唱6 唱fluoro唱7 唱[ 4唱( 4唱methoxybenzoyl )唱
1 唱piperazinyl]唱4唱oxo唱1, 4唱dihydro唱3唱quinoline car唱
boxylic acid (11)
Yield:0畅79 g (79%);M.P.=170℃ ~172℃;IR nmax
cm -1
: 3412 , 3016, 2930, 1719, 1602, 1467, 1433,
1255,1167; 1
H -NMR ( 300 MHz -DMSO -d6):d
8畅6 (s,H,H -2 ) , 7畅9(d,1 H, J =6畅6 Hz,H -5),
7畅6 (d,1H,J =5畅0 Hz.1,H -8 ) , 7畅4 (d,2H, J =
6畅3 Hz,H -3 ′,7′),7畅1(d,2 H,J =6 畅5 Hz, H -4 ′,
6′),3畅8(s,2H, H -11),3畅7 (s,3H, H -8 ′),3畅3
( s,4H, H -16,20),2畅4 (s,4H, H -17,19),1畅3
( d,2H,J =4畅9 Hz, H -13),0畅8(s,2H, H -12);
EIMS m /z (% rel.abund.):465 (M +
,2畅6),420
(4),289 (3),271 (2),230 (3畅6),201 (2),151
(33),135 (74),92 (33),77 (47),56 (50).
1 唱Cyclopropyl唱6 唱fluoro唱4 唱oxo唱7 唱[ 4 唱( 3, 4, 5唱trime唱
thoxybenzoyl )唱1唱piperazinyl ]唱1, 4唱dihydro唱3唱quin唱
oline carboxylic acid (12)
Yield:0畅43 g (43%);M.P.= 280℃ ~282 ℃;IR nmax
cm -1
: 3048 , 3056, 2919, 2855, 1720, 1298, 1622,
1486,1251, 1210; 1
H -NMR (300 MHz -DMSO -
d 6 ):d 15畅1 (s,1H,H -14) ,8畅6 (s,1H,H -2),7畅8
( d,1H,J =4畅7 Hz,H -5),7畅5 (d,1H,J =4畅7 Hz,H
-7),7畅6(d,2H, J =2 畅2 Hz H -3 ′,7′),4畅1(s,
1 H,H -11),3畅7 (s,9H, H -8 ′,9′,10′),3畅6 (s,
4 H,H -16,20),2畅3 (s,4H, H -17,19),1畅9 (s,
2 H,H -13),1畅2 (s,4H, H -12);EIMS m /z (%
rel.abund.):391 (M +
,6),279 (27),197 (2畅5),
167 (53) ,149 ( 100) .
1 -Cyclopropyl -6唱fluoro唱7唱[ 4唱( 1唱naphthoyl )唱1唱
piperazinyl ]唱4唱oxo唱1, 4 唱dihydro唱3唱quinoline car唱
boxylic acid
Yield:0畅70 g (70%);M.P.= 283℃ ~285 ℃;IR nmax
cm -1
: 3480 , 3055, 2931, 1725, 1625, 1478, 1435,
1386,1249, 1204; 1
H -NMR (300 MHz -DMSO -
d 6 ):d 15畅2 (s,1H,H -14) ,8畅6 (s,1H,H -2),8畅0
( d,1H,J =6畅3 Hz,H -5 ) , 7畅5(d,1H,J =5畅0 Hz,
H -8),7畅8(t,1H,J =8畅4 Hz,H -8 ′) ,7畅7 (d,1H,
J =8畅4 Hz,H -6 ′),7畅66 ( d,1H, J =8畅4 Hz, H -
9′),7畅61 (d,1H,J =8畅3 Hz,H -5 ′),7畅5(d,1H,J
=8畅3 Hz, H -3 ′),7畅4(t,1H, J =8 畅4 Hz, H -7 ′)
7畅1 (t,1H, J =8畅3 Hz, H -3′),3畅8 (s,1H, H -
11) ,3畅5 (s,4H, H -16,20),2畅4 (s,4H, H -1 7 ,
19),1畅2 (s,2H,H -13) ,0畅9 (s,2 H,H -12 ) ; EIMS
m /z (% rel.abund.):485 (M +
,0畅39),441 (19),
286 ( 13 ) , 257 ( 36 ) , 245 ( 2畅8),55 (56),127
(61),101 (3),56 (100).
Antibacterial Studies ( In vitro)
191
The synthesized compounds were screened for antibac唱
terial activity against the number <strong>of</strong> Gram -negative
organisms including Klebsiella pneumoniae,Escherichi唱
a coli, Proteus mirabilis, Shigella dysenteriae, Pseudo唱
monas aeruginosa, Salmonella typhi, Salmonella typhi
para,A Salmonella typhi para B and Gram -positive
organisms like Staphylococcus aureus and Bacillus sub唱
tilis by using literature protocol [18]
.In the agar well dif唱
fusion method,wells were duged in the media with the
help <strong>of</strong> a sterile metallic borer with contres at least 24
mm part.Two to eight hours old bacterial inoculums
containing approximately 104 ~106 colony forming
units ( CFU) /ml were spread on the surface <strong>of</strong> nutrient
agar with the help <strong>of</strong> a sterile cotton swab.Cotton swab
was rotated firmly against the upper inside well <strong>of</strong> the
tube to express excess fluid.Entire agar surface <strong>of</strong> the
plate was streaked with the swab three times turning
the plate 60°between each streaking.Recommended
concentration <strong>of</strong> the test sample (2 mg /ml <strong>of</strong> DMSO)
was then added in their respective wells.Other wells
supplemented with DMSO and reference antibacterial
drugs serving as negative and positive controls,respec唱
tively.The plates were incubated immediately at 37 ℃
for 14 ~19 horlater,if necessary.Antibacterial activity
was determined by measuring the diameter <strong>of</strong> zones
showing complete inhibition ( mm).Growth inhibition
was calculated with reference to positive control.
Fungicidal Bioassay ( In vitro)
The synthesized compounds were tested for antifungal
activity against the fungi including Aspergillus flavus,
Trichophyton longifusis,Candida albicans,Microsporum
canis,Fusraium solani and Candida glaberata.Ampho唱
tericin B and miconazol were used as standard drugs.
For tube diffusion test 12 mg <strong>of</strong> sample was dissolved in
1 ml <strong>of</strong> DMSO serving as stock solution.Sabouraud
dextrose agar ( Oxoid, Hampshire, England ) was
seeded with 105 CFU /ml fungal spore suspensions and