Synthesis and antimicrobial studies of thiazolotriazinones

Article abstract of DOI:10.1016/j.ejmech.2010.08.011

A series of 6-substitutedphenyl thiazolo-1,2,4-triazinones (8) were obtained by the initial reaction of 6-substituted arylmethyl-3-mercapto-1,2,4- triazin-5-ones (5) with substituted phenacyl bromides (6) and further followed by PPA cyclization. The struc

Full text of DOI:10.1016/j.ejmech.2010.08.011

European Journal of Medicinal Chemistry 45 (2010) 5039e5043
Contents lists available at ScienceDirect
European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Original article
Synthesis and antimicrobial studies of thiazolotriazinones
*
Mari Sithambaram Karthikeyan
Department of Chemistry, Mangalore University, Mangalagangothri 574199, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of 6-substitutedphenyl thiazolo-1,2,4-triazinones (8) were obtained by the initial reaction of
6-substituted arylmethyl-3-mercapto-1,2,4-triazin-5-ones (5) with substituted phenacyl bromides (6)
and further followed by PPA cyclization. The structures of the newly synthesized compounds were
confirmed by IR, 1H NMR, Mass and analytical data. Compounds 8a, 8e, 8f and 8h exhibited good anti-
microbial activity.
Received 18 November 2009
Received in revised form
31 July 2010
Accepted 6 August 2010
Available online 12 August 2010
Ó 2010 Elsevier Masson SAS. All rights reserved.
Dedicated to my beloved Professor
B. Shivarama Holla on the occasion
of his 64th birthday.
Keywords:
PPA cyclization
Thiazolotriazinones
Antibacterial
Antifungal activities
1. Introduction
herbicides [15], dessicants, plant growth regulators [16] and
insecticides [17]. Meteribuzin and Metamitron are good examples
Thiazole and its derivatives have been much studied in the field
of organic, medicinal chemistry and agriculture. Thiazole bearing
heterocyclic system has found broad application in drug develop-
ment for the treatment of inflammation [1], hypertension [2],
bacterial [3] and HIV infections [4]. Some analogues are used as
fungicides, as an ingredient of herbicides, as schistosomicidal and
anthelmintic drugs [5].
for 1,2,4-triazin-5-ones herbicides [18].
Prompted by these observations it was contemplated to
synthesize a novel series of halogen containing thiazolotriazinones
and to screen them for their antimicrobial activities. The results of
these studies are presented in this paper.
2. Chemistry
Thiazole ring is an important pharmacophore [6] and its coupling
with other rings could furnish new biologically active compounds.
Some of the biologically active molecules bearing thiazole nucleus
are Fanetizole, Meloxicam (anti-inflammatory agent) [7,8], Nizati-
dine (antiulcer agent) [9], Sulfatiazol (antimicrobial agent) [10],
Bleomycine and Tiazofurin (antineoplastic agents) [11].
1,2,4-Triazin-5-ones are also very important class of heterocyclic
compounds that show a wide variety of applications in both the
pharmaceutical and agrochemical industries. As potential human
therapies, 1,2,4-triazin-5-ones have exhibited anticancer [12],
antiulcer [13] and anti-inflammatory effects [14]. Within the
agrochemical field this class of compound has shown activity as
6-Substituted arylmethyl-3-mercapto-1,2,4-triazin-5-ones (5)
were synthesized according to the reported method [19,20].
6-(Substituted arylmethyl)-3-{[2-(substituted phenyl)-2-oxoethyl]
thio}-1,2,4-triazin-5(4H)-one (7) was obtained by reaction of
6-substituted arylmethyl-3-mercapto-1,2,4-triazin-5-ones (5) with
various substituted phenacyl bromides [21] (6) in presence of base.
Compound 7 on cyclization with PPA yielded 3-(4-substituted
arylmethyl)-6-(substituted phenyl)-4H-1,3-thiazolo[2,3-c]-1,2,4-
triazin-5-one (8) in good yields. The reaction sequences are out-
lined in Scheme 1.
3. Results and discussion
* Current address: Syngene International Pvt. Limited, Plot No. 2 & 3, Bomman-
sandra Industrial Area, Jigani link road, Bangalore 560099, India. Tel.: þ91 80 2808
2808; fax: þ91 80 4014 3150.
The IR spectrum of 3-(4-chlorobenzyl)-6-(4-chlorophenyl)-4H-
[1,3]thiazolo[2,3-c][1,2,4]triazin-4-one (8a) showed an absorption
band at 3102 cmꢀ1 indicates the Ar-H stretching. The absorption
E-mail address: karthims02@rediffmail.com.
0223-5234/$ e see front matter Ó 2010 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2010.08.011

5040
M.S. Karthikeyan / European Journal of Medicinal Chemistry 45 (2010) 5039e5043
Where R = 4-Cl, 2,4-Cl ; R = 4-OCH , 4-NO , 4-Cl, 4-Br, 2,4-Cl -5-F
2
1
3
2
2
Scheme 1. Synthesis 6-(substituted phenyl)-4H-1,3-thiazolo[2,3-c]-1,2,4-triazin-5-one (8).
band at 1712 cmꢀ1 due to the presence of eC]O-stretching of the
triazinone ring system. Other prominent absorption bands are
observed at 1542 cmꢀ1 (C]N) and 812 cmꢀ1 (CeCl).
consistent with its molecular formula C18H11Cl2N3OS. The charac-
terization data of thiazolotriazinones (8aej) are given in Table 1.
The 400 MHz 1H NMR spectrum of compound 8a showed
a singlet at
the methylene protons of the benzyl group. The aromatic protons
resonated as four doublets at
7.27 and 7.34 (J ¼ 8.4 Hz), 7.45 and
7.58 (J ¼ 8.8 Hz). The signal due to thiazole ring proton appeared as
a singlet at
7.55. The 400 MHz 13C NMR spectrum of compound 8a
showed the following signal 38.52, 116.28, 124.50, 127.81, 128.35,
128.77, 129.35, 132.23, 132.76, 134.71, 144.69, 150.08, 159.59, 161.79.
Further evidence for the formation of compound 8awas obtained
by recording its mass spectra. The mass spectrum of compound 8a
showed a molecular ion peak at m/z 388 (Mþþ1), which is in
d
3.95 integrating for two protons, which is attributed to
4. Pharmacological studies
d
4.1. Antibacterial studies
d
The newly synthesized compounds were screened for their
antibacterial activity against Escherichia coli, Staphylococcus aureus,
Pseudomonas aeruginosa, Streptococcus pyogenes and Klebsiella
pneumoniae (recultured) bacterial strains by disc diffusion method
[22,23]. The investigation of antibacterial screening data revealed
that all the tested compounds showed moderate to good bacterial

M.S. Karthikeyan / European Journal of Medicinal Chemistry 45 (2010) 5039e5043
5041
Table 1
Characterization data of thiazolotriazinoes (8aej).
Compd. No.
R
R1
Mol. formula
m.p. ꢁ
C
Yield %
Analysis (%) found (calculated)
C
H
N
8a
8b
8c
8d
8e
8f
8g
8h
8i
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Br
4-OCH3
4-NO2
2,4-Cl2-5-F
4-Cl
C18H11Cl2N3OS
C18H11BrClN3OS
C19H14ClN3O2S
C18H11ClN4O3S
C18H9Cl3FN3OS
C18H10Cl3N3OS
C18H10BrCl2N3OS
C19H13Cl2N3O2S
C18H10Cl2N4O3S
C18H8Cl4FN3OS
198e200
245e48
180e83
160e62
220e22
210e12
194e96
135e38
176e78
168e70
73
82
69
62
74
70
75
65
60
73
55.65 (55.81)
49.85 (50.00)
59.27 (59.53)
53.85 (54.27)
48.94 (49.20)
50.95 (51.31)
46.03 (46.35)
54.35 (54.67)
49.81 (50.00)
45.28 (45.66)
2.71 (2.84)
2.37 (2.55)
3.48 (3.66)
2.52 (2.76)
1.91 (2.05)
2.26 (2.38)
2.08 (2.15)
3.05 (3.11)
2.24 (2.31)
1.58 (1.69)
10.63 (10.85)
9.57 (9.72)
10.59 (10.97)
14.07 (13.81)
9.32 (9.57)
9.98 (9.75)
8.93 (9.01)
9.95 (10.07)
12.82 (12.96)
7.42 (7.61)
4-Cl
2,4-Cl2
2,4-Cl2
2,4-Cl2
2,4-Cl2
2,4-Cl2
4-Br
4-OCH3
4-NO2
2,4-Cl2-5-F
8j
inhibition. The compounds 8a, 8e, 8f, 8g, and 8j showed very good
activity against all the bacterial strains.
PPA (0.04 mol) at hot condition and heated to 120 ꢁC for 6 h. The
reaction mixture was cooled and poured onto crushed ice and
neutralized by adding NaHCO3 solution. The resulting solid was
filtered, dried and recrystallized from a mixture of ethanol and
dimethylformamide.
4.2. Antifungal studies
Newly prepared compounds were screened for their antifungal
activity against Aspergillus flavus, Aspergillus fumigatus, Candida
albicans, Penicillium marneffei and Trichophyton mentagrophytes
(recultured) in DMSO by serial plate dilution method [24,25]. The
antifungal screening data showed moderate to good activity.
Compounds 8a, 8e, 8f and 8j emerged as very active against all the
fungal strains.
6.2.1. 6-(4-Bromophenyl)-3-(4-chlorobenzyl)-4H-[1,3]thiazolo
[2,3-][1,2,4]triazin-4-one (8b)
IR (KBr)
n
/cmꢀ1: 3085 (Ar-H), 1718 (C]O), 1532 (C]N), 827
(CeCl); 1H NMR (CDCl3)
d: 3.94 (s, 2H, CH2), 7.34 (d, 2H, Ar-H,
J ¼ 8.2 Hz), 7.46 (d, 2H, Ar-H, J ¼ 8.2 Hz), 7.55 (d, 2H, Ar-H,
J ¼ 8.8 Hz), 7.58 (s,1H, Ar-H), 7.61 (d, 2H, Ar-H, J ¼ 8.8 Hz); 13C NMR
(CDCl3) d: 38.54,116.31,123.67,124.10,127.81,129.35,130.01,130.30,
5. Conclusion
132.23, 132.76, 144.69, 150.08, 159.59, 161.79. MS (m/z, %): 434
(Mþþ1, 34).
The investigation of antibacterial screening data reveals that
among the 10 compounds screened, four compounds showed good
bacterial and fungal inhibition almost equivalent to that of standard.
6.2.2. 3-(4-Chlorobenzyl)-6-(4-methoxyphenyl)-4H-[1,3]thiazolo
[2,3-][1,2,4] triazin-4-one (8c)
IR (KBr)
n
/cmꢀ1: 3100 (Ar-H), 1736 (C]O), 1545 (C]N), 832
6. Experimental
(CeCl); 1H NMR (CDCl3)
d: 3.95 (s, 2H, CH2), 4.02(s, 3H, OCH3), 7.29
(d, 2H, Ar-H, J ¼ 8.4 Hz), 7.35 (d, 2H, Ar-H, J ¼ 8.4 Hz), 7.77 (s,1H, Ar-
H), 7.85 (d, 2H, Ar-H, J ¼ 8.8 Hz), 8.22 (d, 2H, Ar-H, J ¼ 8.8 Hz); 13C
Melting points were determined by open capillary method and
are uncorrected. The IR spectra (in KBr pellets) were recorded on
a Shimadzu FT-IR 157 spectrophotometer. 1H NMR spectra were
recorded either on a Bruker or 300 MHz or 400 MHz NMR spec-
trometer using TMS as an internal standard. The mass spectra were
recorded on a MASPEC low resolution mass spectrometer operating
at 70 eV. The purity of the compounds was checked by thin layer
chromatography (TLC) on silica gel plate using petroleum ether and
ethyl acetate.
NMR (CDCl3) d: 38.54, 55.14, 112.88, 116.28, 118.65, 127.81, 129.35,
129.64,132.23,132.76,144.69,150.08,159.59,160.58,161.79. MS (m/
z, %): 384 (Mþ þ 1, 15).
6.2.3. 3-(4-Chlorobenzyl)-6-(4-nitrophenyl)-4H-[1,3]thiazolo[2,3-
c][1,2,4]triazin-4-one (8d)
IR (KBr)
n
/cm-1: 3091 (Ar-H), 1715 (C]O), 1528 (C]N), 817
(CeCl); 1H NMR(CDCl3)
d
: 4.00 (s, 2H, CH2), 7.29 (d, 2H, Ar-H,
6-Substituted arylmethyl-3-mercapto-triazin-5-(4H)-ones (5)
were synthesized according to reported method [19,20].
Substituted phenacyl bromides were prepared according to repor-
ted method [21].
J ¼ 8.4 Hz), 7.35 (d, 2H, Ar-H, J ¼ 8.4 Hz), 7.77 (s,1H, Ar-H), 7.85 (d,
2H, Ar-H, J ¼ 8.8 Hz), 8.22 (d, 2H, Ar-H, J ¼ 8.8 Hz); MS (m/z, %): 399
(Mþ þ 1, 45).
6.2.4. 3-(4-Chlorobenzyl)-6-(2,4-dichloro-5-fluorophenyl)-4H-[1,3]
thiazolo[2,3-c][1,2,4]triazin-4-one (8e)
6.1. Preparation of 6-(substituted arylmethyl)-3-{[2-
(substitutedphenyl)-2-oxoethyl]thio}-1,2,4-triazin-5(4H)-one (7)
IR (KBr)
n
/cmꢀ1: 3085 (Ar-H), 1731 (C]O), 1526 (C]N), 1098
(CeF), 825 (CeCl); 1H NMR (CDCl3)
d: 3.87 (s, 2H, CH2), 7.19 (d, 2H,
A mixture of appropriate 6-substituted arylmethyl-3-mercapto-
triazin-5-(4H)-ones (5, 0.01 mol), substituted phenacyl bromide
(0.01 mol) and KOH (0.002 mol) in ethanol was refluxed for 5 h. The
reaction mixture was cooled and poured onto crushed ice with
vigorous stirring. The solid obtained was filtered, washed with
water and dried was taken for next step without purification.
Ar-H, J ¼ 8 Hz), 7.25 (d, 2H, Ar-H, J ¼ 8 Hz), 7.61 (s,1H, Ar-H), 7.66 (d,
1H, Ar-H, J ¼ 9.2 Hz), 7.98 (d, 1H, Ar-H, J ¼ 6.8 Hz); MS (m/z, %): 440
(Mþ, 85).
6.2.5. 6-(4-Chlorophenyl)-3-(2,4-dichlorobenzyl)-4H-[1,3]thiazolo
[2,3-c][1,2,4] triazin-4-one (8f)
IR (KBr)
(CeCl); 1H NMR (CDCl3)
7.42e7.44 (m, 1H, Ar-H), 7.57 (s,1H, Ar-H), 7.63e7.65 (m, 3H, Ar-H);
13C NMR (CDCl3)
: 36.88, 116.32, 116.28, 124.50, 127.57,128.35,
n
/cmꢀ1: 3091 (Ar-H), 1725 (C]O), 1530 (C]N), 832
6.2. Preparation of 3-(4-substituted arylmethyl)-6-(substituted
phenyl)-4H-1,3-thiazolo[2,3-c]-1,2,4-triazin-5-one (8)
d: 4.1 (s, 2H, CH2), 7.35e7.38 (m, 3H, Ar-H),
d
6-(Substitutedarylmethyl)-3-{[2-(substitutedphenyl)-2-
oxoethyl]thio}-1,2,4-triazin-5(4H)-one (7, 0.01 mol) was added to
128.44, 128.77, 132.17, 133.01, 134.71, 136.00, 144.69, 150.08, 160.58,
161.79. MS (m/z, %): 424 (Mþ þ 159).

5042
M.S. Karthikeyan / European Journal of Medicinal Chemistry 45 (2010) 5039e5043
Table 3
6.2.6. 6-(4-Bromophenyl)-3-(2,4-dichlorobenzyl)-4H-[1,3]thiazolo
Antifungal activity of thiazolotriazinoes (8aej).
[2,3-c][1,2,4] triazin-4-one (8g)
IR (KBr) n
/cmꢀ1: 3095 (Ar-H), 1712 (C]O), 1533 (C]N), 828
Compd.
no.
Aspergillus Aspergillus Trichophyton
Penicillium Candida
(CeCl); 1H NMR (CDCl3)
d: 4.09 (s, 2H, CH2), 7.27e7.40 (m, 3H, Ar-
fumigatus
flavus
mentagrophytes marneffei
albicans
H), 7.48e7.50 (d, 2H, Ar-H, J ¼ 8.4 Hz), 7.58e7.69 (m, 2H, Ar-H). 13C
8a
8b
8c
8d
8e
8f
8g
8h
8i
22 (6.25)
8 (25)
22 (6.25)
e
25 (6.25)
12 (12.5)
14 (12.5)
7 (25)
21 (6.25)
21 (6.25)
11 (12.5)
17 (6.25)
e
22 (6.25)
e
20 (6.25)
17 (6.25)
11 (12.5)
18 (6.25)
17 (6.25)
18 (6.25)
7 (25)
NMR (CDCl3) d: 36.68, 116.28, 124.10, 127.57, 128.44, 130.01, 130.31,
e
19 (6.25)
e
9 (25)
132.17, 133.01, 134.05, 136.00, 144.69, 150.08, 160.58, 161.79.
15 (6.25)
25 (6.25)
24 (6.25)
12 (12.5)
20 (6.25)
e
21 (6.25)
25 (6.25)
23 (6.25)
e
18 (6.25)
21 (6.25)
16 (6.25)
e
6.2.7. 3-(2,4-Dichlorobenzyl)-6-(4-methoxyphenyl)-4H-[1,3]
thiazolo[2,3-c][1,2,4] triazin-4-one (8h)
n
/cmꢀ1: 3105 (Ar-H), 1729 (C]O), 1545 (C]N), 837
9 (25)
17 (6.25)
e
IR (KBr)
14 (12.5)
21 (6.25)
21 (6.25)
10 (12.5)
25 (6.25)
25 (6.25)
(CeCl); 1H NMR (CDCl3)
d
: 3.98 (s, 2H, CH2), 4.15 (s, 3H, CH3), 7.23
8j
24 (6.25)
22 (6.25)
23 (6.25)
20 (6.25)
19 (6.25)
(d, 2H, Ar-H, J ¼ 8.2 Hz), 7.38e7.42 (m, 3H, Ar-H), 7.61e7.63 (m, 3H,
Standard 25 (6.25)
Ar-H); MS (m/z, %): 418 (Mþ, 11).
e Indicates fungus is resistant to the compounds at >100
given in brackets. MIC (
m
g/ml, MIC values are
m
g/ml) ¼ minimum inhibitory concentration, ie. lowest
6.2.8. 3-(2,4-Dichlorobenzyl)-6-(4-nitrophenyl)-4H-[1,3]thiazolo
concentration to completely inhibit fungal growth. Zone of Inhibition in mm.
Amphotericin B.
[2,3-c][1,2,4] triazin-4-one (8i)
IR (KBr)
n
/cmꢀ1: 3087 (Ar-H), 1710 (C]O), 1525 (C]N), 812
(CeCl); 1H NMR (CDCl3)
d: 4.11 (s, 2H, CH2), 7.35e7.41 (m, 2H, Ar-H),
with approximately 5 105 c.f.u of actively dividing bacteria cells. The
cultures were incubated for 24 h at 37 ꢁC and the growth was
monitored visually and spectrophotometrically. The lowest
concentration (highest dilution) required to arrest the growth of
bacteria was regarded as minimum inhibitory concentrations (MIC).
Ciprofloxacin was used as a standard drug. The diameter of the zone
of inhibition and minimum inhibitory concentration values are
given in Table 2.
7.65e7.66 (m, 1H, Ar-H), 7.73 (d, 2H, Ar-H, J ¼ 8.4 Hz), 7.86 (s,1H, Ar-
H), 8.13 (d, 2H, Ar-H, J ¼ 8.4 Hz).
6.2.9. 3-(2,4-Dichlorobenzyl)-6-(2,4-dichloro-5-fluorophenyl)-4H-
[1,3]thiazolo [2,3-c][1,2,4]triazin-4-one (8j)
IR (KBr)
n
/cmꢀ1: 3099 (Ar-H), 1735 (C]O), 1543 (C]N), 1105
(CeF), 838 (CeCl); 1H NMR (CDCl3)
d: 4.02 (s, 2H, CH2), 7.24e7.29
(m, 2H, Ar-H), 7.42e7.43 (m, 1H, Ar-H), 7.53 (d, 1H, Ar-H, J ¼ 9.6 Hz),
7.61 (s,1H, Ar-H), 7.84 (d, 2H, Ar-H, J ¼ 6.8 Hz); MS (m/z, %): 476
(Mþ þ 1, 79).
7.2. Antifungal assay
Sabourauds agar media was prepared by dissolving 1 g peptone,
7. Pharmacological assay
4 g D
-glucose, and 2 g agar in 100 cm3 distilled water, and adjusting
pH to 5.7 using buffer. Normal saline was used to make a suspension
of spore of fungal strain for lawning. A loopful of particular fungal
strain was transferred to 3 cm3 saline to get a suspension of cor-
responding species. 20 cm3 of agar media was poured in to each
Petri dish. Excess of suspension was decanted and the plates were
dried by placing in a incubator at 37 ꢁC for 1 h. Using an agar punch,
wells were made and each well was labeled. A control was also
prepared in triplicate and maintained at 37 ꢁC for 3e4 d. The
inhibition zones in diameter were measured and compared with
the controls. The Nutrient Broth, which contained logarithmic
serially two fold diluted amount of test compound and controls was
inoculated with approximately 1.6 ꢂ 104e6 104 c.f.u cmꢀ3. The
cultures were incubated for 48 h at 35 ꢁC and the growth was
monitored. The lowest concentration (highest dilution) required to
arrest the growth of fungus was regarded as minimum inhibitory
concentrations (MIC). Amphotericin B was used as the standard
drug. The diameter of zone of inhibition and minimum inhibitory
concentration values are given in Table 3.
7.1. Antibacterial assay
A standard inoculum (1e2 107 c.f.u/cm3 0.5 McFarland stan-
dards) was introduced on to the surface of sterile agar plates, and
a sterile glass spreader was used for even distribution of the inoc-
ulum. The discs measuring 6.25 mm in diameter were prepared
from Whatman no.1 filter paper and sterilized by dry heat at 140 ꢁC
for 1 h. The sterile disc previously soaked in a known concentration
of the test compounds were placed in nutrient agar medium.
Solvent and growth controls were kept. The plates were inverted
and incubated for 24 h at 37 ꢁC. The inhibition zones were
measured and compared with the controls. Minimum inhibitory
concentration (MIC) was determined by broth dilution technique.
The nutrient broth, which contained logarithmic serially two fold
diluted amount of test compound and controls were inoculated
Table 2
Antibacterial activity of thiazolotriazinoes (8aej).
Compd.
no.
Staphylococcus Escherichia Pseudomonas Klebsiella
Streptococcus
Acknowledgement
aureus
coli
aeruginosa
pneumoniae pyogenes
8a
8b
8c
8d
8e
8f
8g
8h
8i
23 (6.25)
23 (6.25)
12 (12.5)
9 (25)
21 (6.25)
21 (6.25)
21 (6.25)
12 (12.5)
20 (6.25)
21 (6.25)
26 (6.25) 33 (6.25)
20 (6.25)
19 (6.25)
19 (6.25)
e
23 (6.25)
21 (6.25)
10 (25)
9 (25)
e
14 (12.5)
14 (12.5)
8 (25)
The author is grateful to The Head of the NMR Research Center,
IISc-Bangalore, and CDRI-Lucknow for providing 1H NMR, and mass
spectral data. The author is also grateful to Dr. N.S. Kumari,
Department of Biochemistry, K.S. Hegde Medical Academy, Dera-
lakatte for providing screening results. M.S.K acknowledges the
financial support (SRF) rendered by CSIR, New Delhi.
25 (6.25)
9 (25)
27 (6.25) 29 (6.25)
29 (6.25) 32 (6.25)
26 (6.25) 29 (6.25)
18 (6.25)
19 (6.25)
18 (6.25)
e
24 (6.25)
23 (6.25)
20 (6.25)
8 (25)
17 (6.25)
24 (6.25)
25 (6.25)
22 (6.25)
e
15 (12.5) 27 (6.25)
29 (6.25) 31 (6.25)
30 (6.25) 33 (6.25)
e
8j
19 (6.25)
22 (6.25)
References
Standarda 23 (6.25)
e Indicates bacteria is resistant to the compounds at >100
given in brackets. MIC (
mg/ml, MIC values are
g/ml) ¼ minimum inhibitory concentration, ie. lowest
[1] F. Haviv, J.D. Ratajczyk, R.W. DeNet, F.A. Kerdesky, R.L. Walters, S.P. Schmidt,
J.H. Holms, P.R. Young, G.W. Carter, J. Med. Chem. 31 (1988) 1719.
m
concentration to completely inhibit bacterial growth. Zone of Inhibition in mm.
[2] W.C. Patt, H.W. Hamilton, M.D. Taylor, M.J. Ryan, D.G.
. Taylor Jr.,
a
Ciprofloxacin was used as standard.
C.J.C. Connolly, A.M. Doherty, S.R. Klutchko, I. Sircar, B.A. Steinbaugh,

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