Synthesis, antioxidant, and antimicrobial evaluation of some 2-arylbenzimidazole derivatives

Article abstract of DOI:10.1016/j.bmcl.2013.05.004

A series of 2-arylbenzimidazole derivatives (3a-3p and 4a-4i) were synthesized and evaluated as potential antioxidant and antimicrobial agents. Their antioxidant properties were evaluated by various in vitro assays including hydroxyl radical (HO) scavenging, superoxide radical anion (O₂ ^-) scavenging, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, and ferric reducing antioxidant power. Results demonstrated that compounds with hydroxyl group at the 5-position of benzimidazole ring had a comparable or better antioxidant activity in comparison to standard antioxidant tert-butylhydroquinone (TBHQ). Markedly, compound 4h that showed the highest HO scavenging activity (EC₅₀ = 46 μM) in vitro had a significant reduction of 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced intracellular oxidative stress and H₂O₂-induced cell death. In addition, these compounds showed moderate to good inhibitory activity against Staphylococcus aureus selectively at noncytotoxic concentrations.

Full text of DOI:10.1016/j.bmcl.2013.05.004

Accepted Manuscript
Synthesis, antioxidant, and antimicrobial evaluation of some 2-arylbenzimida‐
zole derivatives
Binhua Zhou, Baojian Li, Wei Yi, Xianzhang Bu, Lin Ma
PII:
S0960-894X(13)00586-6
DOI:
http://dx.doi.org/10.1016/j.bmcl.2013.05.004
BMCL 20461
Reference:
To appear in:
Bioorganic & Medicinal Chemistry Letters
Received Date:
Revised Date:
Accepted Date:
27 February 2013
29 April 2013
1 May 2013
Please cite this article as: Zhou, B., Li, B., Yi, W., Bu, X., Ma, L., Synthesis, antioxidant, and antimicrobial evaluation
of some 2-arylbenzimidazole derivatives, Bioorganic & Medicinal Chemistry Letters (2013), doi: http://dx.doi.org/
10.1016/j.bmcl.2013.05.004
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Synthesis, antioxidant, and antimicrobial evaluation of some
2-arylbenzimidazole derivatives
Binhua Zhoua, Baojian Lib, Wei Yic, Xianzhang Bua, Lin Ma*, c
a School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510275, P. R. China
b Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China
c Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen
University, P. R. China.
* Corresponding author: Lin Ma, Tel.: +86 20 8411 3690, +86 136 408 02515; e-mail:
cesmal@mail.sysu.edu.cn; Address: Institute of Organic Chemistry, School of Chemistry and Chemical
Engineering, Sun Yat-sen University, Guangzhou, P. R. China.
Abstract
A series of 2-arylbenzimidazole derivatives (3a-3p and 4a-4i) were synthesized and evaluated as
potential antioxidant and antimicrobial agents. Their antioxidant properties were evaluated by various
-
in vitro assays including hydroxyl radical (HO•) scavenging, superoxide radical anion (O2· )
scavenging, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, and ferric reducing antioxidant
power. Results demonstrated that compounds with hydroxyl group at the 5-position of benzimidazole
ring had a comparable or better antioxidant activity in comparison to standard antioxidant
tert-butylhydroquinone (TBHQ). Markedly, compound 4h that showed the highest HO• scavenging
activity (EC50 = 46 μM) in vitro had a significant reduction of
2,2´-azobis(2-amidinopropane)dihydrochloride(AAPH)-induced intracellular oxidative stress and
H2O2-induced cell death. In addition, these compounds showed moderate to good inhibitory activity
against Staphylococcus aureus selectively at non-cytotoxic concentrations.
Key words: 2-arylbenzimidazole; antioxidant; antimicrobial; cytotoxic
1

The homeostatic balance between reactive oxygen species (ROS) and endogenous antioxidants
plays an important role in maintaining healthy tissues. Under oxidative stress, human bodies produce
excessive ROS, resulting in the damage to various cell constituents (such as DNA, lipids and proteins),
consequently causing cell death and health problems.1 Increasing evidence shows that ROS-induced
oxidative damage facilitates the development of a variety of diseases including myocardial infarction,
cancer, neurodegenerative disorders, and inflammation.2-5 Therefore, antioxidants are very important
for protecting living organisms against excessive ROS, and there is special scientific interest to develop
diverse types of antioxidants for medical treatment.
Benzimidazole moiety represents an important pharmacophore and privileged structure in
medicinal chemistry.6 Different substituted benzimidazoles have been associated with an extensive
range of biological activities including antiviral, antifungal, antimicrobial, antiprotozoal,
anti-inflammatory, anticancer, antioxidant, anticoagulant, antidiabetic and antihypertensive
activities.7-17 Specifically, benzimidazole moiety is the fragment of vitamin B12.17 Thereby, great efforts
have been made to expand the library of benzimidazoles and evaluate them for potential bioactivities.18,
19 In this study, we describe the synthesis of some 2-arylbenzimidazole derivatives and screening
results for their antioxidant and antimicrobial activities.
The substituted 2-arylbenzimidazoles 3a-3l were synthesized from various substituted
benzaldehyde and o-nitroaniline (or 4-methoxy-2-nitroaniline) in the presence of Na2S2O4, according to
Yang’s method (Scheme 1).20 The synthetic route for the substituted 2-arylbenzimidazoles 3m-3p is
outlined in Scheme 2. Appropriate substituted benzoyl chlorides 6a-6d were prepared beforehand from
the corresponding benzoic acids, and then reacted with 4-methoxy-2-nitroaniline to yield the
appropriate N-(4-methoxy-2-nitrophenyl)benzamides 7a-7d. These benzamides were reduced by iron
powder, and then cyclized to give 2-arylbenzimidazoles 3m-3p. 5-hydroxy-2-phenylbenzimidazoles
4a-4i were obtained by demethylating the corresponding benzimidazoles 3f-3p in the presence of
hydrobromic acid (Scheme 3). Probably due to large eletronic density or steric hindrance,
demethylation of 2-(2,4-dimethoxyphenyl)-5-methoxy-1H-benzimidazole (3o) in similar conditions
afforded both 2-(2,4-dimethoxyphenyl)-5-hydroxy-1H-benzimidazole (4g) and
2-(4-hydroxy-2-methoxyphenyl)-5-hydroxy-1H-benzimidazole (4h). Similarly, benzimidazole 3p was
selectively demethxylized to yield the corresponding compound 4i.
To determine antioxidant activities of 2-arylbenzimidazoles 3a-3p and 4a-4i, hydroxyl radical
2

-
(HO•) scavenging activity, superoxide anion radical (O2· ) scavenging activity, DPPH radical
scavenging activity, and reducing power were evaluated. The evaluation investigations in vitro were
carried out at different concentrations and compared to the well-known antioxidant TBHQ.
HO• is one of the strongest ROS which reacts with a large number of biomolecules, causing living
organisms damage. Therefore, HO• scavenging activity of compounds is an important antioxidant
activity. The inhibitory activities of 2-arylbenzimidazoles 3a-3p and 4a-4i on HO• (generated by
Fenton reaction) were measured and results were shown in Table 1. Most of compounds exhibited weak
activity (EC50 > 200 M) with the exception of compounds 3g, 4b, 4d, 4e, and 4h. Especially,
compound 4e (EC50 = 77 ±M) showed a bit lower activity than TBHQ (EC50 = 65 ±M), and
compound 4h (EC50 = 46 ±M) showed the highest activity, which had higher activity than TBHQ. A
comparison between compounds 3g and 4b (or 3i vs 4d) suggested that the substitution of hydroxyl
group at the position 5 of benzimidazole ring improved HO• scavenging activity. Meanwhile, the
presence of a di-ortho phenolic motif (catechol) (4e) or a methoxyresorcinol ring (4h) highly increased
HO• scavenging activity compared to compound 4d containing a p-hydroxyphenyl group at the
position 2 of benzimidazole ring.
-
O2· is one of the most representative ROS and usually formed first in cellular oxidation reactions.
-
-
Due to other kinds of free radicals and oxidizing agents produced by O2· , the effects of O2· can be
-
magnified.21 O2· scavenging activities of 2-arylbenzimidazoles 3a-3p and 4a-4i were depicted in Table
1. Compounds 3b, 3g, 3k, and 4b (EC50 = 122 ±, 87 ±, 189 ±, and 169 ± M, respectively)
had higher activity than TBHQ (EC50 > 200 M), but other compounds at 200 M revealed no
-
significant O2· scavenging effects. Additionally, it was noteworthy that an o-hydroxyphenyl group at
-
the position 2 of benzimidazole ring exhibited a major influence for O2· scavenging activity, such as
compounds 3b, 3g, 3k, and 4b. Introduction of a methoxy group at the 5-position of benzimidazole
-
ring could improve O2· scavenging effect (3b vs 3g), while a hydroxyl group at the same position
-
resulted in reduced O2· scavenging activity (3b vs 4b). Compound 3k with a second hydroxyl group at
-
the para-position disclosed weakened O2· scavenging activity compared with its counterpart 3g.
DPPH radical scavenging activity assay is a simple, rapid and convenient method for screening
samples for radical scavenging activity.22 As stable free radicals, DPPH radicals have an absorbance
maximum band at 517 nm (a deep purple color). The purple color of DPPH solution is usually bleached
in the presence of antioxidants, which provide a free radical (such as hydrogen atoms and electron
3

donation) for pairing DPPH odd electron. Thus reduction of DPPH absorption at 517 nm represents the
capacity of antioxidants to scavenge free radical. DPPH radical scavenging activities of
2-arylbenzimidazoles 3a-3p and 4a-4i were determined and listed in Table 1. Compounds 4a-4i,
containing hydroxyl group at the position 5 of benzimidazole ring, displayed almost the same activity
of TBHQ (EC50 = 36 ± M). Rest of the compounds (EC50 > 200 M) showed no noteworthy
activities, with the exception of compounds 3k (EC50 = 129 ±M) and 3l (EC50 = 58 ± M).
Compounds 4f, 4h, and 4i showed the highest level of scavenging activities (EC50 = 26 ±, 27 ±, and
23 ± M, respectively). Based on above results, DPPH radical scavenging activity of compounds was
much dependent on hydroxyl group substituent at the position 5 of benzimidazole ring. When a
methoxy group was at the 5-position of benzimidazole ring, a di-meta phenolic motif (resorcinol) (3k)
or a methoxypyrocatechol ring (3l) at the 2-position of benzimidazole ring highly improved DPPH
radical scavenging activity.
In simple terms, non-enzymatic antioxidants could be described as reductants, and reducing power
of antioxidants analogously refers to their antioxidant activity. Reducing power of compounds 4a-4i,
which showed more promising DPPH radical scavenging activities, were determined using ferric
reducing antioxidant power (FRAP) assay23 and results were presented in Fig. 1. FRAP values of
synthesized compounds and TBHQ demonstrated an increase in a concentration dependent manner. All
synthesized compounds, with the exception of compound 4h, possessed a comparable or better
reducing power in comparison with TBHQ. Therefore, hydroxyl group at the position 5 of
benzimidazole ring may play a crucial role for a ferric reducing antioxidant.
According to above in vitro studies, compound 4h that showed the highest HO• scavenging
activity (EC50 = 46 M) was chosen for cellular antioxidative activity assays. A549 cells were
pretreated with AAPH for 1 h to induce ROS stress, and then compound 4h was added to decrease
AAPH-induced oxidative stress. To monitor intracellular level of oxidative stress, DCFH-DA, a
specific oxidation-sensitive fluorescent dye for measuring hydrogen peroxides and hydroxyl radicals,
was used to quantify generation of intracellular ROS. As shown in Fig. 2, treatment of compound 4h
remarkably decreased AAPH-induced oxidative stress in A549 cells, as observed by fluorescence
images of DCFH-DA staining. Flow cytometric analysis further identified that compound 4h (50 M
and 100 M) obviously inhibited AAPH-induced oxidative stress by 25.3 ± 3.3 % and 70.4 ± 8.5%,
respectively (Fig. 3). In addition, A549 cells were pretreated with compound 4h (50 M and 100 M)
4

for 1 h, and then exposed to H2O2 (500 M) for 24 h followed by SRB assay for evaluating cell
viability. Results showed that H2O2 (500 M) reduced A549 cell viability to less than 10% of the
control, while compound 4h treatment rescued oxidative injury of H2O2 (Fig. 4), suggesting that
compound 4h exhibited effectively antioxidative activity in cellular system.
2-arylbenzimidazoles 3a-3p and 4a-4i were screened in vitro for antimicrobial activity against
Gram-negative (E. coli, P. aeruginosa) and Gram-positive (S. aureus, B. cereus, S. albus) bacteria by
the conventional agar dilution method. Minimum inhibitory concentration (MIC) and minimum
bactericidal concentration (MBC) values were evaluated and ciprofloxacin was used as a standard
reference drug (Table 2). MIC values of 2-arylbenzimidazoles against E. coli indicated that some
compounds exhibited moderate to good activity but were lower active than ciprofloxacin (MIC = 0.39
M). Compounds 3a, 3j, 3k, and 4b (MIC = 6.25 M) showed the most potent inhibitory activity
against E. coli. However, all tested compounds showed no significant inhibitory activity against
another Gram-negative bacterium (P. aeruginosa, MIC > 200 M). Compounds 3c, 4f, and 4g (MIC =
0.39, 0.78, and 0.39 M, respectively) possessed a comparable inhibitory activity against S. aureus
compared with ciprofloxacin (MIC = 0.39 M). Compounds 4a, 4b, 4c, and 4d with hydroxyl group at
the 5-position exhibited potent inhibitory activities against S. aureus (MIC = 1.56 M of all), implying
that the hydroxyl group at the 5 position of benzimidazole ring may positively affect antimicrobial
activity of compounds. Inhibitory activities of compounds 3a-3p and 4a-4i (MIC > 100 M) against S.
albus were much poorer than that of ciprofloxacin (MIC = 0.39 M). Most of tested compounds also
showed poor or no activity against another Gram-positive bacterium (B. cereus, MIC ≥ 25 M).
Compounds 3h, 3m, 4b, 4c, and 4f displayed the maximum activity against B. cereus (MIC = 25 M of
all). These results indicated that these compounds possessed selective antimicrobial activities and
further development of such compounds might be of interest.
For further pharmacological study, cytotoxic properties of compounds 3a-3p and 4a-4i against
normal mouse fibroblast cell line (NIH/3T3) were investigated using SRB assay (Table 2). All
synthesized compounds and ciprofloxacin showed no significant toxicity against NIH/3T3 cells at the
concentration of 200 M (IC50 > 200 M) after 48 h incubation, suggesting that tested compounds
displayed antimicrobial activities in vitro at non-cytotoxic concentrations.
In conclusion, twenty-five 2-arylbenzimidazole derivatives were synthesized and studied for their
-
antioxidant activities in vitro (HO• scavenging activity, O2· scavenging activity, DPPH radical
5

scavenging activity, reducing power) and in cellular system, antimicrobial activities, and cytotoxic
activities. Antioxidant data indicated that compounds with hydroxyl group substituent at the 5-position
showed significant reducing power and promising radical scavenging activity on HO• and DPPH
radicals in vitro, among which compound 4h exhibited effectively antioxidative activity in cellular
system. Some of tested compounds demonstrated excellent antimicrobial activity against S. aureus at
non-cytotoxic concentrations, among which compounds 3c and 4g were as active as the standard drug
(ciprofloxacin). These results suggested that these molecules might serve as interesting lead
compounds for the development of new antioxidant and/or antimicrobial agents.
Acknowledgments
We are indebted to National Nature Science Foundation of China (No. 30973619 & 81172931) for
financial support of this study.
References and notes
1. Boonstra, J.; Post, J. A. Gene 2004, 337, 1.
2. Reuter, S.; Gupta, S. C.; Chaturvedi, M. M.; Aggarwal, B. B. Free Radic. Biol. Med. 2010, 49,
1603.
3. Dumont, M.; Beal, M. F. Free Radic. Biol. Med. 2011, 51, 1014.
4. Al Ghouleh, I.; Khoo, N. K.; Knaus, U. G.; Griendling, K. K.; Touyz, R. M.; Thannickal, V. J.;
Barchowsky, A.; Nauseef, W. M.; Kelley, E. E.; Bauer, P. M.; Darley-Usmar, V.; Shiva, S.;
Cifuentes-Pagano, E.; Freeman, B. A.; Gladwin, M. T.; Pagano, P. J. Free Radic. Biol. Med. 2011, 51,
1271.
5. Zhang, Y.; Tocchetti, C. G.; Krieg, T.; Moens, A. L. Free Radic. Biol. Med. 2012, 53, 1531.
6. Spasov, A. A.; Yozhitsa, I. N.; Bugaeva, L. I.; Anisimova, V. A. Pharm. Chem. J. 1999, 33, 232.
7. Achar, K. C.; Hosamani, K. M.; Seetharamareddy, H. R. Eur. J. Med. Chem. 2010, 45, 2048.
8. Bauer, J.; Kinast, S.; Burger-Kentischer, A.; Finkelmeier, D.; Kleymann, G.; Rayyan, W. A.;
Schroppel, K.; Singh, A.; Jung, G.; Wiesmuller, K. H.; Rupp, S.; Eickhoff, H. J. Med. Chem. 2011, 54,
6993.
9. El-Nassan, H. B. Eur. J. Med. Chem. 2012, 53, 22.
10. Garudachari, B.; Satyanarayana, M. N.; Thippeswamy, B.; Shivakumar, C. K.; Shivananda, K. N.;
Hegde, G.; Isloor, A. M. Eur. J. Med. Chem. 2012, 54, 900.
11. Li, Y. F.; Wang, G. F.; He, P. L.; Huang, W. G.; Zhu, F. H.; Gao, H. Y.; Tang, W.; Luo, Y.; Feng, C.
L.; Shi, L. P.; Ren, Y. D.; Lu, W.; Zuo, J. P. J. Med. Chem. 2006, 49, 4790.
12. Mavrova, A.; Vuchev, D.; Anichina, K.; Vassilev, N. Eur. J. Med. Chem. 2010, 45, 5856.
13. Mizuno, C. S.; Chittiboyina, A. G.; Shah, F. H.; Patny, A.; Kurtz, T. W.; Pershadsingh, H. A.;
Speth, R. C.; Karamyan, V. T.; Carvalho, P. B.; Avery, M. A. J. Med. Chem. 2010, 53, 1076.
14. Neochoritis, C. G.; Zarganes-Tzitzikas, T.; Tsoleridis, C. A.; Stephanidou-Stephanatou, J.;
6

Kontogiorgis, C. A.; Hadjipavlou-Litina, D. J.; Choli-Papadopoulou, T. Eur. J. Med. Chem. 2011, 46,
297.
15. Patel, R. V.; Patel, P. K.; Kumari, P.; Rajani, D. P.; Chikhalia, K. H. Eur. J. Med. Chem. 2012, 53,
41.
16. Wu, X. Q.; Qiao, W.; Yan, S. J.; Li, F.; Li, N. L.; Ma, L. Acta Sci. Natur. Univ. Sunyatseni 2007,
46, 59.
17. Bansal, Y.; Silakari, O. Bioorg. Med. Chem. 2012, 20, 6208.
18. Charifson, P. S.; Grillot, A. L.; Grossman, T. H.; Parsons, J. D.; Badia, M.; Bellon, S.; Deininger,
D. D.; Drumm, J. E.; Gross, C. H.; LeTiran, A.; Liao, Y. S.; Mani, N.; Nicolau, D. P.; Perola, E.;
Ronkin, S.; Shannon, D.; Swenson, L. L.; Tang, Q.; Tessier, P. R.; Tian, S. K.; Trudeau, M.; Wang, T. S.;
Wei, Y. Y.; Zhang, H.; Stamos, D. J. Med. Chem. 2008, 51, 5243.
19. Keurulainen, L.; Salin, O.; Siiskonen, A.; Kern, J. M.; Alvesalo, J.; Kiuru, P.; Maass, M.;
Yli-Kauhaluoma, J.; Vuorela, P. J. Med. Chem. 2010, 53, 7664.
20. Fokas, D.; Yang, D.; Li, J.; Yu, L.; Baldino, C. M. Synthesis 2005, 47.
21. Liu, F.; Ooi, V. E.; Chang, S. T. Life Sci. 1997, 60, 763.
22. Koleva, II; van Beek, T. A.; Linssen, J. P.; de Groot, A.; Evstatieva, L. N. Phytochem. Anal. 2002,
13, 8.
23. Benzie, I. F.; Strain, J. J. Anal. Biochem. 1996, 239, 70.
7

Illustrations captions:
Scheme 1. Synthesis of compounds 3a–3e.
Scheme 2. Synthesis of compounds 3m–3p.
Scheme 3. Synthesis of compounds 4a–4i.
Figure 1. Reducing power of 2-arylbenzimidazoles 4a-4i and TBHQ. Each value is expressed as mean
± SD (n = 3).
Figure 2. Inhibition of compound 4h on AAPH-induced oxidative stress in A549 cells as measured by
fluorescence morphological examination. Cells were pretreated with AAPH and then exposed to
compound 4h as described in Supporting Information. Magnifications, ×200. Results were from one
representative in three independent experiments.
Figure 3. Inhibition of compound 4h on AAPH-induced oxidative stress in A549 cells as measured by
flow cytometric analysis. Cells were pretreated with AAPH and then exposed to compound 4h as
described in Supporting Information. Results were from one representative in three independent
experiments.
Figure 4. Inhibition of H2O2-induced cell death in A549 cells by compound 4h. Cells were pretreated
with compound 4h and then exposed to H2O2 following evaluated by SRB assay as described in
Supporting Information (means ± SD; n = 3). *p < 0.05.
8

-
Table 1 IC50 values of 2-arylbenzimidazoles 3a-3p and 4a-4i for HO•, O2· and DPPH free radical
scavenging activities. TBHQ is used as the standard reference.a
Scavenging activity (EC50, µM)
Compounds
-
HO•
>200
DPPH
>200
O2·
>200
3a
3b
3c
>200
122 ± 17
>200
>200
>200
>200
3d
3e
>200
>200
>200
>200
>200
>200
3f
>200
>200
>200
3g
3h
3i
190 ± 5
>200
87 ± 13
>200
>200
>200
>200
>200
>200
3j
>200
>200
>200
3k
3l
>200
189 ± 15
>200
129 ±7
58 ± 5
>200
>200
3m
3n
3o
3p
4a
4b
4c
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
42 ± 2
30 ± 3
40 ± 2
34 ± 2
33 ± 1
26 ± 2
32 ± 1
27 ± 2
23 ± 3
36 ± 1
124 ± 10
>200
169 ± 11
>200
4d
4e
159 ± 9
77 ± 6
>200
>200
>200
4f
>200
4g
4h
4i
>200
>200
46 ± 4
>200
>200
>200
TBHQ
65 ± 2
>200
a Data shown are average values from there independent experiments with SD.
9

Table 2 Antibacterial and cytotoxic activities of 2-arylbenzimidazoles 3a-3p and 4a-4i. Ciprofloxacin is
used as the standard reference.
MICa (MBCb) (M)
IC50 (M)
Compounds
E.
P.
S.
S.
albus
>200
B.
NIH/3T3
coli
aeruginosa aureus
cereus
>200
3a
6.25 (100)
25 (100)
12.5 (100)
25 (100)
12.5 (50.0)
25 (100)
100 (>200)
12.5 (100)
12.5 (100)
6.25 (100)
6.25 (100)
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
0.78 (0.78)
100 (>200)
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
3b
>200
>200
3c
0.39 (0.78)
12.5 (50.0)
1.56 (1.56)
>200
>200
50.0 (200)
>200
3d
>200
3e
100 (100)
>200
50.0 (100)
50.0 (200)
200 (>200)
25.0 (200)
50.0 (200)
3f
3g
>200
>200
3h
100 (200)
100 (200)
>200
3i
>200
3j
25.0 (200) 100 (>200) 50.0 (200)
3k
50.0 (100)
100 (200)
100 (200)
>200
50.0 (100)
50.0 (200)
3l
3m
>200
50.0 (200) 100 (>200) 25.0 (100)
3n
>200
>200
>200
100 (200)
>200
>200
>200
3o
>200
6.25 (50.0)
6.25 (50.0)
1.56 (1.56)
3p
>200
100 (200)
50.0 (100)
4a
100 (>200)
6.25 (25.0)
100 (>200)
>200
>200
4b
1.56 (1.56) 100 (>200) 25.0 (25.0)
4c
1.56 (1.56)
1.56 (1.56)
>200
>200
>200
>200
>200
>200
>200
>200
25.0 (50.0)
50.0 (50.0)
100 (>200)
25.0 (25.0)
50.0 (50.0)
>200
4d
4e
>200
4f
>200
0.78 (0.78)
0.39 (0.39)
>200
4g
12.5 (25)
12.5 (25)
>200
4h
4i
>200
100 (>200)
Ciprofloxacin
0.39 (0.39)
0.39 (0.39) 0.39 (0.39) 0.39 (0.39)
a MIC Minimum Inhibitory Concentration (M)
b MBC Minimum Bactericidal Concentration (M)
10

Scheme 1.
11

Scheme 2.
12

Scheme 3.
13

Figure 1

Figure 2

Figure 2-gray scale

Figure 3

Figure 4

*Graphical Abstract (for review)
Synthesis, antioxidant, and antimicrobial evaluation of some
2-arylbezimidazole derivatives
Binhua Zhou, Baojian Li, Wei Yi, Xianzhang Bu, Lin Ma*
Twenty-five 2-arylbezimidazole derivatives were synthesized and their potential antioxidant and
antimicrobial activities were evaluated in our present study.