Synthesis and antimicrobial evaluation of 5-aryl-1,2,4-triazole-3-thione derivatives containing a rhodanine moiety

Article abstract of DOI:10.1016/j.bmcl.2015.04.081

Three series of 5-aryl-1,2,4-triazole-3-thione derivatives containing a rhodanine moiety (5a-k, 6a-i, and 7a-i) have been synthesized, characterized and evaluated for their antibacterial activity. Some of these displayed potent antibacterial activity against several Gram-positive and Gram-negative bacterial strains (including multidrug-resistant clinical isolates) with minimum inhibitory concentration (MIC) values in the range of 4-64 μg/mL and minimum bactericidal concentration (MBC) values in the range of 8-256 μg/mL. Compared with previously reported rhodanine derivatives, these compounds exhibited a broad spectrum of antibacterial activity by means of introducing 4-amino-5-aryl-1,2,4-triazole-3-thione moiety. Notably, compound 5f exhibited good antibacterial activity against Staphylococcus aureus RN 4220, S. aureus 209, S. aureus 503, Gram-negative bacteria (Escherichia coli 1924), and Candida albicans 7535 with MBC values of 8 or 16 μg/ml. All of the compounds synthesized in the current Letter were characterized by ¹H NMR, ¹³C NMR, infrared and mass spectroscopy.

Full text of DOI:10.1016/j.bmcl.2015.04.081

Accepted Manuscript
Synthesis and antimicrobial evaluation of 5-aryl-1, 2, 4-triazole-3-thione deriv-
atives containing a rhodanine moiety
Chao Li, Jia-Chun Liu, Ya-Ru Li, Cheng Gou, Mei-Ling Zhang, Hong-Yan Liu,
Xiao-Zhen Li, Chang-Ji Zheng, Hu-Ri Piao
PII:
S0960-894X(15)00413-8
DOI:
http://dx.doi.org/10.1016/j.bmcl.2015.04.081
BMCL 22664
Reference:
Bioorganic & Medicinal Chemistry Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
5 November 2014
11 April 2015
23 April 2015
Please cite this article as: Li, C., Liu, J-C., Li, Y-R., Gou, C., Zhang, M-L., Liu, H-Y., Li, X-Z., Zheng, C-J., Piao,
H-R., Synthesis and antimicrobial evaluation of 5-aryl-1, 2, 4-triazole-3-thione derivatives containing a rhodanine
moiety, Bioorganic & Medicinal Chemistry Letters (2015), doi: http://dx.doi.org/10.1016/j.bmcl.2015.04.081
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Synthesis and antimicrobial evaluation of 5-aryl-1, 2,
4-triazole-3-thione derivatives containing a rhodanine
moiety
Chao Li, Jia-Chun Liu, Ya-Ru Li, Cheng Gou, Mei-Ling Zhang, Hong-Yan Liu,
Xiao-Zhen Li, Chang-Ji Zheng*, Hu-Ri Piao*
Key Laboratory of Natural Resources and Functional Molecules of the Changbai
Mountain, Affiliated Ministry of Education; Yanbian University College of Pharmacy,
Yanji 133002, P. R. China
*Correspondence Author: Tel: + 86(433)243-5003; Fax: + 86(433)243-5004.
E-mail: piaohuri@yahoo.com.cn (H. R. Piao).
*Correspondence Author: Tel: + 86(433)243-6015; Fax: + 86(433)243-5026.
E-mail: zhengcj@ybu.edu.cn(C. J. Zheng).
Abstract
Three series of 5-aryl-1, 2, 4-triazole-3-thione derivatives containing a rhodanine
moiety (5a–k, 6a–i, and 7a–i) have been synthesized, characterized and evaluated for
their antibacterial activity. Some of these displayed potent antibacterial activity
against several Gram-positive and Gram-negative bacterial strains (including
multidrug-resistant clinical isolates) with minimum inhibitory concentration (MIC)
values in the range of 4–64 µg/mL and minimum bactericidal concentration (MBC)
values in the range of 8–256 µg/mL. Compared with previously reported rhodanine
derivatives, these compounds exhibited a broad spectrum of antibacterial activity by
means of introducing 4-amino-5-aryl-1,2,4-triazole-3-thione moiety. Notably,
compound 5f exhibited good antibacterial activity against S.aureus RN 4220, S.
aureus 209, S. aureus 503, Gram-negative bacteria (Escherichia coli 1924), and
Candida albicans 7535 with MBC values of 8 or 16µg/ml. All of the compounds

1
13
synthesized in the current paper were characterized by H NMR, C NMR, infrared
and mass spectroscopy.
Keywords: Rhodanine; 1, 2, 4-Triazole derivatives; Antibacterial activity; Minimum
inhibitory concentration; Minimum bactericidal concentration.
Antibiotic resistance is becoming a serious threat to public healthcare and there is
an urgent need for novel antimicrobial agents.1-5 Heterocyclic compounds have
antifungal and anticancer properties and are currently used therapeutically.6-8
4-Amino-5-aryl-1,2,4-triazole-3-thione derived compounds
have
attracted
considerable attention because of their antimicrobial activity against several strains of
bacteria.9-10
In previous work, we identified a series of rhodanine-3-acetic acid derivatives11-14
which showed remarkable bacteriostatic activity against Gram-positive bacteria. An
example is compound A with a minimum inhibitory concentration (MIC) value of 2
µg/mL (Fig. 1).15 Unfortunately, none of the compounds were active against
Gram-negative bacteria, even at 64 µg/mL. In contrast, compound B exhibited a good
antibacterial activity against Escherichia.coli with an MIC value of 6.25 µg/mL (Fig.
1).16 Thus, as a part of our ongoing studies towards the development of novel
antibacterial agents, compounds A and B were used as leads to design novel
compounds. Here, we reported the synthesis, characterization, and antimicrobial
assessment of three series of 5-aryl-1,2,4-triazole-3-thione derivatives containing a
rhodanine moiety (5a–k, 6a–i and 7a–i).
Compounds 5a-k, 6a-i, and 7a-i were synthesized according to the synthetic route
depicted in Scheme 1. Esterification between the R-substituted aromatic acid and
ethanol in the presence of concentrated sulfuric acid afforded the corresponding ester
which was further reacted with 85% hydrazine monohydrate in ethanol to get
hydrazide 1. The intermediate 2 was obtained by the reaction of hydrazide 1 and
carbon disulfide (CS2) in the presence of KOH in absolute methanol. The rhodanine
intermediates 3 were prepared according to a method previously described in the

literature.17-18 Compounds 4 were prepared by the Knoevenagel condensation reaction
of terephthaldicarboxaldehyde with intermediates 3 in ethanol in the presence of
glacial acid and piperidine.19 The target compounds 5a-k, 6a-i, and 7a-i were
synthesized by reacting R-substituted 4-amino-5-aryl-1, 2, 4-triazole-3-thione 2 with
the appropriate N-substituted rhodanine 4 in glacial acetic acid. The structures of the
1
synthesized compounds were confirmed by IR, H NMR, 13C NMR, and mass
spectroscopy.20
Twenty-nine synthesized compounds were screened for their in vitro antibacterial
activities with a minimum inhibitory concentration (MIC) method. Their MBC values
were also determined (only for the compounds with MIC values of ≤64µg/mL). The
results are summarized in Table 1, Table 2, Table 3 and Table 4.
The in vitro antibacterial activity was evaluated using a 96-well microtiter plate to
obtain the MIC values for different strains (including multidrug-resistant clinical
isolates). Gatifloxacin and moxifloxacin were used as positive controls. Four
Gram-positive strains (S. aureus RN 4220, S. aureus KCTC 209, S. aureus KCTC 503,
Streptococcus mutans 3065), five Gram-negative strains (Escherichia coli KCTC
1924, Escherichia coli CCARM 1356, Pseudomonas aeruginosa 2742, Pseudomonas
aeruginosa 2004, Salmonella typhimurium 2421) and one fungus (Candida albicans
7535) were used to the evaluation. MBC were defined as the minimum bactericidal
concentration that yielded no colonies for the corresponding agar subculture after the
proper incubation interval. The MBC values of these compounds were determined
against S.aureus RN 4220, S. aureus 209, S. aureus 503, S.mutans 3065, Escherichia
coli 1924, Candida albicans 7535 and multidrug-resistant S.aureus. Gatifloxacin and
moxifloxacin were used as positive controls and DMSO as a negative control.
The results indicated that most of the compounds strongly inhibited the
Gram-positive bacteria with MIC values in the range of 4–64 µg/mL. Some of them
also exhibited moderate to good levels of inhibition against the Gram-negative strain
(Escherichia coli KCTC 1924) with MIC values in the range of 8–64 µg/mL.
Especially, Compound 5f exhibited good inhibitory activity against fungus (Candida
albicans 7535) with MIC values of 4 or 8 µg/mL. Compounds 5a–k displayed higher

inhibition against the three Gram-positive strains (S. aureus RN 4220, S. aureus
KCTC 503, Streptococcus mutans 3065) than those in series 6a–i and 7a–i, as shown
in Table 1. MBC values of several compounds were the same or 2-4-fold higher than
their MICs. Among them, compounds 5a, 5c–h had identical or 2-fold higher MIC
values than their MBCs against S.aureus RN 4220. Compound 5f demonstrated an
MBC value of 2-fold higher than its MIC against S. aureus 209 and an identical MIC
and MBC values against Candida albicans 7535. The MBC/MIC ratio of the
compounds 5a-f and 5h-k were ≤4 for S. aureus 503,21 and most of them displayed
MBCs at 2-4 fold higher than their MICs against S.mutans 3065. Six compounds (5b,
5f, 5i, 6d, 6g, 7a) showed good antibacterial activities (MBC/MIC ratio≤4) against
Escherichia coli 1924. Most derivatives, in general, exhibited high levels of
antibacterial activity but were less active than the controles, as shown in Table 2.22
The MIC values against the clinical isolates of multidrug-resistant Gram-positive
bacterial strains are reported in Table 3.22 Most of the compounds exhibited inhibitory
activity towards the multidrug-resistant Gram-positive bacterial strains (MRSA
CCARM 3167 and 3506, QRSA CCARM 3505 and 3519) with MIC values in the
range of 8–64 µg/mL. Especially, compound 5a showed the most potent inhibitory
effect with an MIC value of 8 µg/mL. The MBC values against the clinical isolates of
multidrug-resistant S.aureus, as shown in Table 4, showed that compounds 5a, 5b, 5e,
5f, 5h and 5i exhibited good antibacierial activities against MRSA CCARM 3167 and
3506 with MBCs in the range of 8–64 µg/mL. Compounds 5a, 5f and 5h displayed
moderate antibacterial activity with MBC value of 32 µg/mL against QRSA CCARM
3505 and 3519. Although these compounds are less active than the controles, the
results are encouraging and provide further clues towards the discovery of new
antimicrobial agent.
Structure-activity relationships were observed from this study. First, the
aforementioned results suggested that the antibacterial activity was not significantly
affected by the position and physicochemical properties of the substituents on the
phenyl ring. Second, a comparison of the activities across the three different series of
compounds, a general antibacterial activity order of 5a-k > 7a-i > 6a-i was obtained,

which indicated that a free carboxyl group on the rhodanine ring is not critical for the
activity against Gram-positive bacteria and the introduction of phenylpropanoic acid
is beneficial for the improvement of antibacterial activity. Third, none of the
rhodanine derivatives previously reported by our group showed any activity against
the
Gram-negative
strain.
Nevertheless,
the
introduction
of
an
4-amino-5-aryl-1,2,4-triazole-3-thione moiety resulted in moderate antibacterial levels
against the Gram-negative strain E. coli 1924, indicating that an 4-amino-5-aryl-1, 2,
4-triazole-3-thione moiety is critical for the improvement of the activities against the
Gram-negative strain, which might be a hit for further optimization of
4-amino-5-aryl-1,2,4-triazole-3-thione derivatives.
In conclusion, based on our previous work, three novel series of
5-aryl-1,2,4-triazole-3-thione derivatives containing a rhodanine moiety (5a–k, 6a–i,
and 7a–i) have been designed, synthesized and evaluated for their antibacterial
activity against Gram-positive and Gram-negative bacteria. The results showed that
most of the compounds have good levels of antibacterial activity against
Gram-positive bacteria (including multidrug-resistant strains of clinical isolates).
The results indicate that these hybrid compounds containing a phenylpropionic acid
group at the N-3 position of the heterocycle ring play an important role and, compared
to our previous work, the introduction of the 4-amino-5-aryl-1,2,4-triazole-3-thione
moiety might be beneficial to increase the potency against Gram-negative strains.
Further modification of these compounds including the study of possible mechanism
of action is currently underway in our laboratories.
Acknowledgment
This work was supported by the National Science Foundation of China (Grant
numbers 81260468 and 81060257).
Supplementary data
Supplementary data associated with this article can be found in the online version.

References and notes
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20. Preparation of 5f:
Compound
2f
(1
mmol)
and
(S)-2-((Z)-5-(4-formylbenzylidene)-4-oxo-2-thioxothiazolidin-3-yl)-3-phenylpropanoi
c acid (1 mmol) were refluxed in glacial acetic acid (7 mL) at 100–110 °C for 4–6 h.
The excess solvent was removed under reduced pressure. The resultant solid was
washed with water and purified with silica gel column chromatography, eluting with
DCM/methanol (100:1) to get a yellow solid. Yield 75％. m.p. 158–160 oC. IR (KBr)
cm–1: 1714 (C=O), 1604 (C=N). 1H NMR (DMSO-d6, 300 MHz, ppm): δ 3.52 (s, 2H,
CH2), 5.88 (s, 1H, CH), 7.82 (s, 1H, CH=), 7.14-7.97 (m, 13H, Ar-H), 8.47 (s, 1H,
CH=N), 12.10 (s, 1H, COOH). 13C NMR (DMSO–d6, 300 MHz, ppm): δ 193.11,
169.14, 166.92, 164.47, 162.28, 147.46, 136.98, 135.67, 134.47, 133.78, 133.51,
132.22, 131.84, 131.05, 129.46, 128.77, 128.46, 127.86, 127.23, 127.01, 121.78,
58.69, 33.48. EIMS m/z 606 (M+1).
21. French, G. L. J. Antimicrob. Chemother. 2006, 58, 17.
22. Anti-bacterial activity assay: The micro-organisms used in the present study were
S. aureus RN 4220, S. aureus KCTC 209, S. aureus KCTC 503, Streptococcus mutans
3065, Escherichia coli KCTC 1924, Escherichia coli CCARM 1356, Pseudomonas
aeruginosa 2742, Pseudomonas aeruginosa 2004, Salmonella typhimurium 2421 and
one fungus (Candida albicans 7535). The strains of multidrug-resistant clinical
isolates were methicillin-resistant Staphylococcus aureus (MRSA CCARM 3167 and
MRSA CCARM 3506) and quinolone-resistant Staphylococcus aureus (QRSA
CCARM 3505 and QRSA CCARM 3519). Clinical isolates were collected from
various patients hospitalized in several clinics. The in vitro antimicrobial activity was
evaluated using the minimum inhibitory concentration (MIC) and minimum
bactericidal concentration (MBC) with different strains. Gatifloxacin and
moxifloxacin were used as positive controls. The bacteria were grown to mid-log

phase in Mueller-Hinton broth and diluted 1000-fold in the same medium. Stock
solutions of the test compounds in dimethyl sulfoxide were prepared and then poured
into 96-well plates. The final concentration of 64±0.5 µg/mL underwent a two-fold
serial dilution. The microbacteria were suspended and contained approximately 105
CFU/mL. These were applied to 96-well plates with a serial dilution and incubated at
37 °C for 24 h. The microbacterial growth was measured from the absorption at 630
nm. This was done using a microtiter, enzyme-linked immunosorbent assay (ELISA)
reader. MBCs were determined by plating 5 µL of samples from each MIC assay tube
which showed no visible growth of bacterial onto freshly prepared Mueller Hinton
agar plates and plates were incubated at 37 ºC for additional 24 h. The MBC was
defined as the lowest concentration of the test sample at which did not permit any
visible bacterial colony growth on the agar plates during the period of incubation. All
experiments were carried out in triplicate.

Table 1.
Inhibitory activity of compounds 5a-k, 6a-i and 7a-i expressed as MIC (µg/mL) against strains of Gram-positive
(Staphylococcus aureus and Streptococcus mutans) bacteria and Gram-negative (Escherichia coli, Salmonela typhinurium and
Pseudomonas aeruginosa) bacteria and Candida albicans 7535.
Gram-positive strains
Gram-negative strains
Fungus
Compound
R
S. aureus
S. mutans
E.coli
P. aeruginosa S. typhinurium C.albicans
4220a
209b
503c
8
3065d
1924e 1356f
2742g
2004h
2421i
7535j
5a
5b
5c
5d
5e
5f
H
8
16
>64
8
8
>128
64
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128 >128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>64
>64
>64
>64
>64
8
2-CH3
3-CH3
4-CH3
2-Cl
3-Cl
4-Cl
2-Br
3-Br
4-Br
4-F
>64
>64
>64
>64
8
16
32
64
64
64
>128
>128
>128
8
8
64
16
16
16
8
8
4
5g
5h
5i
8
>64
>64
>64
>64
>64
>64
>64
>64
>64
>64
>64
>64
>64
64
16
16
>128
>128
64
>64
>64
>64
>64
>64
>64
>64
>64
>64
>64
>64
>64
>64
>64
>64
>64
>64
>64
>64
>64
>64
>64
8
8
8
32
64
64
5j
8
8
16
>128
>128
>128
32
5k
6a
6b
6c
6d
6e
6f
16
32
64
H
>64
>64
>64
64
>64
64
>64
>64
>64
>64
>64
>64
>64
>64
>64
16
3-CH3
4-CH3
2-Cl
3-Cl
4-Cl
2-Br
4-Br
4-F
>64
>64
>64
>64
>64
>64
>64
32
>128
64
>64
>64
64
>128
>128
64
6g
6h
6i
>64
64
>128
>128
32
7a
7b
7c
7d
7e
7f
H
32
64
3-CH3
4-CH3
2-Cl
3-Cl
4-Cl
2-Br
4-Br
32
>64
>64
64
32
>64
>64
16
32
>64
32
>64
16
>128
16
>64
>64
16
>64
>64
64
>64
>64
16
>64
>64
16
>128
>128
16
7g
7h
>64
>64
>64
>64
64

7i
4-F
>64
0.25
0.25
>64
2
>64
4
>64
0.5
>128
>128
16
>128 >128
>128
0.5
>64
0.5
0.5
Gatifloxacin
2
1
1
Moxifloxacin
2
2
0.25
2
128
1
2
0.5
a
S.aureus RN 4220. b S. aureus 209. c S. aureus 503. d S.mutans 3065. e E.coli KCTC 1924. f E.coli CCARM 1356.
P.aeruginosa 2742. h P. aeruginosa 2004. i S. typhimurium 2421. j C.albicans 7535
g
S.aureus RN 4220: A genotype of S.aureus. KCTC (Korean Collection for Type Cultures) CCARM (Culture Collection
Antimicrobial Resistant Microbes)
Table 2.
MICs and MBCs (minimum bactericidal concentrations) (both in µg/mL) of some compounds (MIC≤64µg/mL) against
S.aureus RN 4220, S. aureus 209, S. aureus 503, S.mutans 3065, Escherichia coli 1924 and Candida albicans 7535.
Compound
R
4220
MIC/MBC
8/16
209
503
MIC/MBC
8/8
3065
MIC/MBC
8/16
1924
7535
MIC/MBC
MIC/MBC
MIC/MBC
5a
H
5b
2-CH3
3-CH3
4-CH3
2-Cl
3-Cl
4-Cl
2-Br
3-Br
4-Br
4-F
16/64
32/32
8/8
16/32
64/128
64/64
16/64
8/16
8/16
64/64
5c
64/256
64/>256
16/>128
4/>32
5d
5e
16/32
8/8
5f
8/16
8/8
8/8
5g
8/16
16/128
8/8
16/32
5h
8/16
8/32
5i
32/256
8/64
64/128
8/32
64/>128
16/64
64/64
5j
5k
16/128
32/128
64/>256
64/256
6b
3-CH3
2-Cl
2-Br
4-F
32/>256
64/128
64/256
6d
64/256
64/>256
64/>256
32/>256
32/>256
32/>256
16/128
6g
6i
64/>256
64/>256
7a
H
32/>256
32>256
16>256
16/>128
16/>128
32/128
32/256
16/>128
16/>128
64/>256
2/2
7b
3-CH3
2-Cl
2-Br
4-Br
7d
64/>256
64/>256
16/>128
16/>128
7g
7h
Gatifloxacin
Moxifloxacin
0.25/0.25
0.25/0.25
2/2
2/2
4/4
2/2
0.5/0.5
0.5/0.5
0.5/0.5
0.25/0.25
2/2
Blank: MIC > 64µg/mL, MBC not tested.

Table 3. Inhibitory activity (MIC, µg/mL) of compounds 5a-k,6a-i and 7a-i against clinical isolates of multidrug-resistant
S.aureus.
Multidrug-resistant S.aureus
Compound
R
MRSA
QRSA
3167a
3506b
8
3505c
8
3519d
8
5a
5b
5c
5d
5e
5f
H
8
16
16
8
2-CH3
3-CH3
4-CH3
2-Cl
3-Cl
4-Cl
2-Br
3-Br
4-Br
4-F
16
16
16
16
16
16
16
16
16
16
8
16
16
16
16
8
8
5g
5h
5i
8
16
16
16
8
16
8
8
32
8
16
16
32
5j
16
8
8
5k
6a
6b
6c
6d
6e
6f
16
64
16
16
H
>64
64
>64
>64
>64
>64
>64
>64
>64
>64
>64
32
>64
64
>64
64
3-CH3
4-CH3
2-Cl
3-Cl
4-Cl
2-Br
4-Br
4-F
>64
>64
>64
>64
64
>64
>64
>64
>64
>64
>64
>64
32
16
>64
>64
>64
64
6g
6h
6i
>64
16
>64
32
7a
7b
7c
7d
7e
H
32
32
3-CH3
4-CH3
2-Cl
3-Cl
64
32
32
32
>64
16
>64
16
>64
16
>64
16
>64
>64
>64
>64

7f
4-Cl
2-Br
4-Br
4-F
>64
16
>64
16
>64
16
>64
16
7g
7h
>64
>64
2
>64
>64
2
>64
>64
8
>64
>64
4
7i
Gatifloxacin
Moxifloxacin
1
1
4
4
a Methicillin-resistant S. aureus CCARM 3167. b Methicillin-resistant S. aureus CCARM 3506.
c Quinolone-resistant S. aureus CCARM 3505. d Quinolone-resistant S. aureus CCARM 3519.
Table 4. MICs and MBCs (both in µg/mL) of some compounds (MIC≤64µg/mL) against clinical isolates of
multidrug-resistant S.aureus.
Compound
R
3167
MIC/MBC
8/16
3506
MIC/MBC
8/32
3505
MIC/MBC
8/32
3519
MIC/MBC
8/32
5a
H
5b
2-CH3
3-CH3
4-CH3
2-Cl
3-Cl
4-Cl
2-Br
3-Br
4-Br
4-F
16/32
16/128
8/64
16/64
16/64
16/>128
16/128
16/>128
16/>128
8/32
5c
16/64
16/64
5d
16/128
16/64
16/128
16/>128
8/32
5e
16/32
8/8
5f
16/16
5g
8/64
16/128
16/32
16/64
16/128
8/32
5h
8/16
8/32
5i
32/128
8/32
16/64
16/128
8/32
32/256
8/64
5j
16/128
64/>256
5k
16/128
64/>256
16/128
64/>256
16/128
64/>256
16/>128
64/>256
32/>256
32/>256
32/>256
16/>128
16/>128
4/4
6b
3-CH3
4-CH3
2-Br
4-F
6c
6g
64/256
16/>128
32/>256
64/>256
16/>128
16/>128
2/2
6i
7a
H
32/>256
32/>256
16/>128
16/>128
2/2
32/>256
32/>256
16/>128
16/>128
8/8
7b
3-CH3
2-Cl
2-Br
7d
7g
Gatifloxacin
Moxifloxacin
1/1
1/1
4/4
4/4
Blank: MIC > 64µg/mL, MBC not tested.

Figure 1. Previously reported compound A, B and the structure-based design of the
target compounds.

Scheme 1. Synthetic scheme for the synthesis of compounds 5a-k, 6a-i and 7a-i.

Synthesis and antimicrobial evaluation of 5-aryl-1, 2,
4-triazole-3-thione derivatives containing a rhodanine
Chao Li, Jia-Chun Liu, Ya-Ru Li, Cheng Gou, Mei-Ling Zhang, Hong-Yan Liu,
Xiao-Zhen Li, Chang-Ji Zheng*, Hu-Ri Piao*
Key Laboratory of Natural Resources and Functional Molecules of the Changbai
Mountain, Affiliated Ministry of Education; Yanbian University College of Pharmacy,
Yanji 133002, P. R. China