Catecholthioether derivatives: Preliminary study of in-vitro antimicrobial and antioxidant activities

Article abstract of DOI:10.1248/cpb.59.1149

In this research, synthesis, antimicrobial and antioxidant activities of a series of catecholthioethers having benzoxazole and tetrazole moieties are described. Antimicrobial activity was evaluated by minimum inhibitory concentration (MIC) assay. The synthesized compounds were tested in vitro against three Gram-positive bacteria including Staphylococcus aureus (clinical isolated), Staphylococcus aureus ATCC 25922, Enterococcus faecium (clinical isolated), and two Gram-negative bacteria including Klebsiella pneumoniae (clinical isolated) and Pseudomonas aeruginosa 27853 and the yeast Candida albicans in comparison with control drugs. Microbiological results indicated that the synthesized compounds possessed a broad spectrum of activity against the tested microorganisms at MIC values between 4-256μg/ml. This shows compounds having tetrazole moiety were the most active against Gram-negative strains, whereas compounds having benzoxazole moiety were more active against Gram-positive ones. Also both of them showed significant antifungal activity against Candida albicans and had lower activity than the compared control drugs (Sulfamethoxazole and Fluconazole). The antioxidant activity was assessed using two methods, including, 1,1-biphenyl-2-picrylhydrazyl (DPPH) radical scavenging, and reducing power assays. Some of the catecholthioether derivatives showed antioxidant activity more than Trolox and butylated hydroxyanisole (BHA) as reference antioxidants.

Full text of DOI:10.1248/cpb.59.1149

September 2011
Note
Chem. Pharm. Bull. 59(9) 1149—1152 (2011)
1149
Catecholthioether Derivatives: Preliminary Study of in-Vitro
Antimicrobial and Antioxidant Activities
Hadi ADIBI, ,a Atefeh RASHIDI,b Mohammad Mehdi KHODAEI,c Abdolhamid ALIZADEH,c
*
e
Mohammad Bagher MAJNOONI,a Narges PAKRAVAN,c Ramin ABIRI,d and Davood NEMATOLLAHI
a Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences; b Students
Research Committee, Kermanshah University of Medical Sciences; d Department of Microbiology, Faculty of Medicine,
Kermanshah University of Medical Sciences; Kermanshah 67145–6173, Iran: c Chemistry Department, Faculty of
Chemistry and Nanoscience and Nanotechnology Research Center (NNRC), Razi University; Kermanshah 67149, Iran:
and e Faculty of Chemistry, Bu-Ali Sina University; Hamadan 65174, Iran.
Received May 10, 2010; accepted June 28, 2011; published online June 30, 2011
In this research, synthesis, antimicrobial and antioxidant activities of a series of catecholthioethers having
benzoxazole and tetrazole moieties are described. Antimicrobial activity was evaluated by minimum inhibitory
concentration (MIC) assay. The synthesized compounds were tested in vitro against three Gram-positive bacteria
including Staphylococcus aureus (clinical isolated), Staphylococcus aureus ATCC 25922, Enterococcus faecium
(clinical isolated), and two Gram-negative bacteria including Klebsiella pneumoniae (clinical isolated) and
Pseudomonas aeruginosa 27853 and the yeast Candida albicans in comparison with control drugs. Microbiologi-
cal results indicated that the synthesized compounds possessed a broad spectrum of activity against the tested
mg/ml. This shows compounds having tetrazole moiety were the
microorganisms at MIC values between 4—256
most active against Gram-negative strains, whereas compounds having benzoxazole moiety were more active
against Gram-positive ones. Also both of them showed significant antifungal activity against Candida albicans
and had lower activity than the compared control drugs (Sulfamethoxazole and Fluconazole). The antioxidant
activity was assessed using two methods, including, 1,1-biphenyl-2-picrylhydrazyl (DPPH) radical scavenging,
and reducing power assays. Some of the catecholthioether derivatives showed antioxidant activity more than
Trolox and butylated hydroxyanisole (BHA) as reference antioxidants.
Key words catecholthioether; benzoxazole; tetrazole; antioxidant activity; antimicrobial activity
Growing evidence suggests that RNOS (reactive nitrogen
and oxygen species) involved in the damage of biomolecules,
contributes to etiology of several human diseases.1) Several
studies reported the antioxidant activity of plant extracts and
their relationship with the phenolic compound content.2—6) o-
and p-Dihydroxybenzenes are ubiquitous in nature. Their
functionalized derivatives are extensively used in chemical
and pharmaceutical industries as well as synthetic intermedi-
ates in the manufacturing of food antioxidants.7—9)
The Catechol and its mono-substituted derivatives (with
OH, CH3, OCH3, CHO, and COOH groups) are active in part
against Pseudomonas, Bacillus, but not penicillium
species.10) Recent observation suggests that benzoxazoles
possess potential activity with lower toxicities in the
chemotherapeutic approach in man,11,12) inhibiting activity on
eukaryotic topoisomerase II enzyme in cell-free system,13—16)
Fig. 1. Structures of Biologically Active Tetrazolic Thioethers
anti-tumor,17) anticosulavant,18) antifungal,19) antiallergic,20)
antituberculosis,21) antiproliferative,22) and antiviral activ-
ities.23—25)
Due to a broad spectrum of activities reported in the litera-
ture so far, we have prepared a number of catecholthioethers
Tetrazolic thioethers have also found widespread use in the having benzoxazole38) and tetrazole39) moieties for evaluating
modern approach to the synthesis of biologically active com- their antimicrobial and antioxidant activities (Chart 1).
pounds and various drugs. This interest stems from the abil-
ity of tetrazoles to mimic the carboxylic acid group, which Results and Discussion
has motivated the incorporation of tetrazoles into biological
Antimicrobial Activity Catecholthioether derivatives
active molecules.26—31) For example, as it is shown in Fig. 1, 1A—5A and 1B—3B have been synthesized through elec-
the compound I derivatives has well-known antiviral and trooxidative-Michael type reactions of catechols with 1-
anti-inflammatory properties,32,33) 1-aryl-thiotetrazolyl acet- phenyl-5-mercaptotetrazole or 2-mercaptobenzoxazole and
anilides (II, III) have demonstrated activities as human im- characterized by spectral data as shown in Chart 1. The anti-
munodeficiency virus-1 (HIV-1) non-nucleoside reverse tran- microbial activity of the synthesized compounds 1A—5A
scriptase inhibitors,34—36) and 1-phenyl-5-arylthiotetrazole and 1B—3B were tested in vitro against three Gram-positive
(IV) is used as activating reagent in RNA synthesis.37)
bacteria (clinical isolated of Staphylococcus aureus, Staphy-
© 2011 Pharmaceutical Society of Japan
∗ To whom correspondence should be addressed. e-mail: hadibi@kums.ac.ir

1150
Vol. 59, No. 9
lococcus aureus ATCC 25922, clinical isolated of Enterococ- synthesized compounds, 4A was more potent against all the
cus faecium), two Gram-negative bacteria (clinical isolated screened microorganisms showing MIC values between 16—
of Klebsiella pneumoniae and Pseudomonas aeruginosa 128 mg/ml. Moreover, the compounds 2B and 3B (MIC value
27853), and the yeast Candida albicans by using twofold se- for both 64 mg/ml) are found to be the most active derivatives
rial dilution technique,40,41) and were compared with control against Gram-negative bacteria (P. aeruginosa) which is
drugs (Sulfamethoxazole and Fluconazole). All the biologi- often resistant to antibiotic therapy. Finally, regarding to high
cal results of the compounds are given in Table 1. The syn- hydrophilicity of the synthesized tetrazolic and benzoxazolic
thesized compounds showing minimum inhibitory concentra- compounds, they showed more effect on Gram-negative bac-
tion (MIC) values between 8—256 mg/ml are able to inhibit teria than Gram-positive ones. However, the comparison be-
in vitro growth of the screened microorganisms and Table 1 tween 1A and 4A shows that the smaller the size of the sub-
showed lower antibacterial activity against the screened mi- stitution, the higher the potency of the compound.
croorganisms than the reference drugs. It could be noticed
The synthesized compounds were also tested against Can-
that most of the compounds were more active as antifungal dida albicans for their antifungal activity and possessed MIC
than as antibacterial, which could guide us to design further values between 4—16 mg/ml. However, the compound 2A
new antifungal compounds. Also it may be concluded that which had methoxy substitution at position C-5 could inhibit
the influence of the substitution of R1 and R2 on the cate- in vitro growth of Candida albicans having the same in-
cholic moiety at positions C-5 and C-6 is important for hav- hibitory activity as fluconazole (MIC value 4 mg/ml). No dif-
ing antibacterial and antifungal activities.
ference was observed between all the other compounds hav-
The results reported in Table 1 showed that both benzoxa- ing MIC values 16 mg/ml. Furthermore we found that elec-
zole and tetrazole rings had the same effect to inhibit in vitro tron-donating substitutions (methoxy and methyl) on the
growth of screened microorganisms. However, among the catecholic ring at positions C-5 and C-6 increased antifungal
activity.
Antioxidant Activity The antioxidant activity was as-
sessed using two methods, including, 1,1-biphenyl-2-picryl-
hydrazyl (DPPH) radical scavenging,42) and reducing
power43) assays according to the methods described in the lit-
erature (Table 2). The results of antioxidant activity in both
methods are approximately similar to each other. All the syn-
thesized compounds except 5A exhibited very good antioxi-
dant properties. They were also more potent than BHA and
Trolox as reference compounds. It should be noted that when
electron-donating groups are added to the catecholic ring at
positions C-5 and C-6, the antioxidant activity is increased.
This is due to the stabilization of the generated radical during
oxidation (Fig. 2). The compounds 1A, 2A, and 3A have well
antioxidative activity with a major activity for 2A (IC50 0.17,
1.56 mM). The results of antioxidant activity indicated that in
addition to catecholic moiety, tetrazolic and benzoxazolic
rings were also effective and necessary in the assays. How-
ever, it is seems that benzoxazole moiety is more potent than
tetrazole one due to delocalizing free electron during oxida-
tion. For example, compounds 1B, 2B, and 3B showed an-
tioxidative activity having IC50 values 0.15, 0.28 and 1.5 mM
respectively via DPPH method, whereas tetrazolic similari-
ties (1A, 2A, 4A) have IC50 values 1.55 and 0.17, and 4.5 mM
respectively via the same assay. Overall, the result of DPPH
assay was relatively consistent with that of reducing power
Chart 1. Synthetic Routes of Catecholthioethers through Electro-Organic
Pathway
Table 1. The MICs (in mg/ml) Values of Catecholthioethers against Bacteria and Fungus
E. faecium
(Clinical isolated)
K. pneumoniae
(Clinical isolated)
S. aureus
(Clinical isolated)
S. aureus
ATCC 25922
P. aeruginosa
ATCC 27853
Candida albicans
(Clinical isolated)
Compound
1A
2A
3A
4A
5A
1B
2B
128
64
128
64
256
256
256
256
—
64
128
16
16
16
256
128
128
—
256
256
256
64
256
64
16
32
—
4
256
128
128
64
128
256
256
64
128
128
128
128
128
256
64
64
—
8
16
4
16
16
16
16
16
16
4
3B
Fluconazole
Sulfamethoxazole
—
2
4
8
—

September 2011
1151
Table 2. The IC50 (in mM) Values of Catecholthioethers According to
45), 230 (9), 213 (6), 155 (80), 118 (100), 93 (17), 77 (17), 65 (21); HR-MS
(EI) Calcd for C14H12O2N4S 300.0681, Found 300.0675.
DPPH Radical Scavenging, and Reducing Power Assays
4-Methyl-5-(1-phenyl-1H-tetrazol-5-ylthio)benzene-1,2-diol (4A)39)
mp 169—171 °C; yield 65%; IR (KBr) cmꢁ1: 690, 715, 723, 821, 874, 1050,
IC50
1
Entry
Compound
1098, 1130, 1198, 1250, 1450, 1490, 1529, 1601, 2902, 3075, 3480; H-
DPPH
Reducing power
NMR d ppm (200 MHz, DMSO-d6): 2.16 (s, 3H), 6.76 (s, 1H), 6.95 (s, 1H),
7.66—7.70 (m, 5H), 9.22—9.48 (broad, 2H); 13C-NMR d ppm (50 MHz,
DMSO-d6): 19.5, 113.1, 117.9, 122.6, 124.9, 129.9, 130.7, 133.2, 133.3,
144.0, 148.0, 154.3; MS (EI, 70 eV) 300 (Mꢂ, 46), 267 (21), 155 (64), 118
(100), 93 (17), 91 (18), 77 (12), 65 (16); HRMS (EI) Calcd for C14H12O2N4S
300.0681, Found 300.0686.
1
2
1A
2A
1.55
0.17
0.31
4.5
3.22
1.56
2.67
3.8
3
3A
4
5
6
7
8
9
10
4A
5A
1B
2B
3B
Trolox
BHA
4-(1-Phenyl-1H-tetrazol-5-ylthio)benzene-1,2-diol (5A)39) mp 135—
136 °C; yield 92%; 1H-NMR d ppm (200 MHz, DMSO-d6): 4.51 (broad,
2H), 6.79—7.01 (m, 3H), 7.58—7.69 (m, 5H); 13C-NMR d ppm (50 MHz,
DMSO-d6): 114.3, 116.4, 121.4, 125.1, 126.1, 129.9, 130.7, 133.1, 146.2,
147.8, 154.5; MS (EI, 70 eV) 286 (Mꢂ, 23), 141 (48), 118 (100), 91 (10), 77
(10), 65 (6); HR-MS (EI) Calcd for C13H10O2N4S 286.0524, Found
286.0512.
10
17.23
1.55
2.54
3.28
4.1
0.15
0.28
1.5
5
4.8
3.9
5-(Benzo[d]oxazol-2-ylthio)-3-methoxybenzene-1,2-diol (1B)38) mp
157—159 °C; IR (KBr) cmꢁ1: 679, 743, 810, 1000, 1095, 1109, 1132, 1203,
1217, 1237, 1298, 1332, 1356, 1452, 1511, 1605, 2841, 2940, 2995, 3040,
3510; 1H-NMR d ppm (200 MHz, DMSO-d6): 3.75 (s, 3H), 5.46 (broad,
1H), 6.80 (s, 1H), 6.91 (s, 1H), 7.22 (m, 2H), 7.46 (m, 2H); 13C-NMR d
ppm (50 MHz, DMSO-d6): 56.6, 110.7, 110.9, 113.6, 116.6, 119.0, 124.9,
125.1, 137.3, 141.9, 146.9, 149.2, 151.7, 164.1; MS (EI, 70 eV) 289 (Mꢂ,
100), 202 (10.2), 171 (22.4), 152 (12.2), 128 (12.3), 85 (19.4), 63 (20.4), 39
(42.8). Anal. Calcd for C14H11NO4S: C, 58.13; H, 3.80; N, 4.84; S, 11.07.
Found: C, 58.08; H, 3.75; N, 4.74; S, 11.11.
assay. The potencies for the antioxidative activity of the test
compounds compared to the reference drugs are in the
following order: 1Bꢀ2Aꢀ2Bꢀ3Aꢀ1Aꢀ3Bꢀ4AꢀBHAꢀ
Troloxꢀ5A.
In summary, we have reported biological evaluation of
catecholthioether derivatives, which represent antioxidant
and antimicrobial activities. All of the synthesized catechol-
thioethers showed some antimicrobial activity. A strong anti-
oxidant activity was obtained against reducing power and
DPPH radical scavenging, showing more potent than the
compared control drugs Trolox and BHA.
4-(Benzo[d]oxazol-2-ylthio)-5-tert-butylbenzene-1,2-diol (2B)38) mp
168—171 °C; IR (KBr) cmꢁ1: 651, 744, 811, 859, 961, 1099, 1138, 1213,
1
1240, 1291, 1364, 1416, 1456, 1501, 1597, 2866, 2963, 3013, 3506; H-
NMR d ppm (200 MHz, DMSO-d6): 1.24 (s, 9H), 7.06—7.52 (m, 6H), 5
(broad, 2H); 13C-NMR d ppm (50 MHz, DMSO-d6): 31.4, 34.0, 110.2,
112.0, 115.8, 118.6, 122.3, 124.4, 124.6, 141.9, 142.6, 144.9, 145.9, 151.5,
163.4; MS (EI, 70 eV) 315 (Mꢂ, 77.5), 300 (100), 152 (55.1), 91 (28.6), 63
(12.2), 39 (20.4). Anal. Calcd for C17H17NO3S: C, 64.76; H, 5.39; N, 4.44; S,
10.15. Found: C, 64.66; H, 5.45; N, 4.35; S, 10.22.
Experimental
Electro-Organic Synthesis of Catecholthioethers In a typical proce-
dure, a solution (ca. 100 ml) of water/acetonitrile (90/10), containing 0.2 M
acetate sodium, 1.0 mmol of catechols and 1.0 mmol of 1-phenyl-5-mercap-
totetrazole, was electrolyzed in an undivided cell equipped with a carbon
anode (an assembly of four rods, 6-mm diameter, and 10-cm length), and a
large platinum gauze cathode at 0.20 V vs. SCE, at 25 °C. The electrolysis
was terminated when the decay of the current became more than 95%. The
process was interrupted during the electrolysis and the graphite anode was
washed in acetone in order to reactivate it. At the end of electrolysis, a few
drops of acetic acid were added to the solution and the cell was placed in a
refrigerator overnight. The precipitated solid was collected by filtration,
washed copiously with distilled water and characterized by spectral data and
were compared with those reported in the literature.38,39) The final products
(1A—5A, 1B—3B) were obtained purely and no extra purification was
needed.38,39)
4-(Benzo[d]oxazol-2-ylthio)-5-methylbenzene-1,2-diol (3B)38) mp
198—200 °C; IR (KBr) cmꢁ1: 641, 745, 815, 869, 1003, 1096, 1134, 1236,
1
1270, 1354, 1380, 1424, 1454, 1496, 1599, 3078, 3427, 3523; H-NMR d
ppm (200 MHz, DMSO-d6): 2.23 (s, 3H), 6.85 (s, 1H), 7.2 (m, 3H), 7.5 (m,
2H), 9.3 (broad, 2H); 13C-NMR d ppm (50 MHz, DMSO-d6): 20.1, 110.7,
113.3, 118.5, 118.9, 123.6, 124.7, 125.0, 134.1, 141.9, 144.5, 148.6, 151.7,
164.0; MS (EI, 70 eV) 273 (Mꢂ, 100), 240 (72.9), 222 (18.6), 194 (30.5),
166 (78), 108 (23.7), 91 (22.0), 65 (35.6), 39 (54.2). Anal. Calcd for
C14H11NO3S: C, 61.53; H, 4.03; N, 5.12; S, 11.72. Found: C, 61.45; H, 4.10;
N, 5.20; S, 11.65.
Acknowledgment We gratefully acknowledge the Kermanshah Univer-
sity of Medical Sciences Research Council for financial support.
4-tert-Butyl-5-(1-phenyl-1H-tetrazol-5-ylthio)benzene-1,2-diol (1A)39)
mp 181—183 °C; yield 59%; IR (KBr) cmꢁ1: 560, 610, 691, 700, 725, 880,
943, 1055, 1090, 1155, 1287, 1340, 1355, 1401, 1490, 1539, 1599, 2902,
References
1) Yamaguchi L. F., Lago J. H., Tanizak T. M., Dimassio P., Kato M. J., J.
Photochem., 16, 1838—1843 (2006).
1
3088, 3510; H-NMR d ppm (200 MHz, DMSO-d6): 1.12 (s, 9H), 6.80 (s,
1H), 6.91 (s, 1H), 7.63—7.80 (m, 5H), 9.08 (broad, 1H), 9.56 (broad, 1H);
13C-NMR d ppm (50 MHz, DMSO-d6): 31.1, 33.8, 112.1, 114.8, 120.8,
124.8, 129.7, 130.5, 133.3, 142.0, 143.8, 145.4, 153.2; MS (EI, 70 eV) 342
(Mꢂ, 100), 298 (9), 283 (10), 255 (7), 197 (22), 180 (35), 164 (24), 135
(14), 118 (46), 91 (15), 77 (14), 65 (9); HR-MS (EI) Calcd for C17H18O2N4S
342.1150, Found 342.1152.
2) Aaby K., Hvattum E., Skrede G., Food Chem., 52, 4595—4603
(2004).
3) Silva B. A., Ferreres F., Malva J. O., Dias A. C. P., Food Chem., 90,
157—167 (2005).
4) Singh R., Singh S., Kumar S., Arora S., Food Chem., 103, 505—511
(2007).
5) Sun T., Ho C. T., Food Chem., 90, 743—749 (2005).
6) Uan Y. V., Bone D. E., Carrington M. F., Food Chem., 91, 485—494
(2005).
7) Ganapati D. Y., Salim A. R., Navinchandra S. A., Int. Eng. Chem. Res.,
44, 7969—7977 (2005).
8) Lau S. S., Monks T. J., Everitt J. I., Kleymenova E., Walker C. L.,
Chem. Res. Toxicol., 14, 25—33 (2001).
9) Abdel-Lateff A., König G. M., Fisch K. M., Höller U., Jones P. G.,
Wright A. D., J. Nat. Prod., 65, 1605—1611 (2002).
10) Pauli A., “Proceedings of the Third World Congress on Alleopathy,”
Tsukuba, Japan, 2002, pp. 26—30.
11) Haugwitz R. D., Angel R. G., Jacobs G. A., Maurer B. V., Narayanan
V. L., Cruthers L. R., Szanto J., J. Med. Chem., 25, 969—974 (1982).
12) Hisano T., Ichikawa M., Tsumoto K., Tasaki M., Chem. Pharm. Bull.,
3-Methoxy-5-(1-phenyl-1H-tetrazol-5-ylthio)benzene-1,2-diol (2B)39)
1
mp 82—83 °C; yield 58%; H-NMR d ppm (200 MHz, DMSO-d6): 3.69 (s,
3H), 6.61—670 (m, 2H), 7.62—7.69 (m, 5H), 8.75—9.40 (broad); 13C-
NMR d ppm (50 MHz, DMSO-d6): 56.0, 109.7, 113.8, 115.4, 124.9, 125.1,
129.9, 130.7, 133.2, 136.5, 146.4, 148.6, 149.7, 154.3; MS (EI, 70 eV) 316
(Mꢂ, 32), 256 (4), 230 (5), 171 (100), 156 (10), 118 (65), 84 (38), 77 (8), 65
(6); HR-MS (EI) Calcd for C14H12O3N4S 316.0630, Found 316.0625.
3-Methyl-5-(1-phenyl-1H-tetrazol-5-ylthio)benzene-1,2-diol (3A)39)
mp 160—161 °C; yield 76%; IR (KBr) cmꢁ1: 653, 695, 710, 810, 847, 910,
1
1083, 1302, 1428, 1490, 1520, 1610, 2993, 3050, 3450; H-NMR d ppm
(200 MHz, DMSO-d6): 2.16 (s, 3H), 6.70 (d, Jꢃ8.34 Hz, 1H), 6.94 (d,
Jꢃ8.34 Hz, 1H), 7.66—7.74 (m, 5H), 8.67 (broad, 1H), 9.86 (broad, 1H);
13C-NMR d ppm (50 MHz, DMSO-d6): 14.0, 113.2, 114.6, 124.9, 127.3,
129.2, 130.0, 130.7, 133.2, 144.4, 147.7, 154.5; MS (EI, 70 eV) 300 (Mꢂ,

1152
Vol. 59, No. 9
30, 2996—3004 (1982).
Acad. Sci. U.S.A., 101, 5628—5633 (2004).
13) Pinar A., Yurdakul P., Yildiz I., Temiz-Arpaci O., Acan N. L., Aki-
Sener E., Yalcin I., Biochem. Biophys. Res. Commun., 317, 670—674
(2004).
14) Temiz-Arpaci O., Tekiner-Gulbas B., Yildiz I., Aki-Sener E., Yalcin I.,
Bioorg. Med. Chem., 13, 6354—6359 (2005).
27) Rajasekaran A., Thampi P. P., Eur. J. Med. Chem., 39, 273—279
(2004).
28) Crenshaw R. R., Luke G. M., Bialy G., J. Med. Chem., 15, 1179—
1180 (1972).
29) Ichikawa T., Kitazaki T., Matsushita Y., Hosono H., Yamada M.,
Mizuno M., Itoh K., Chem. Pharm. Bull., 48, 1947—1953 (2000).
30) Ichikawa T., Yamada M., Yamaguchi M., Kitazaki T., Matsushita Y.,
Higashikawa K., Itoh K., Chem. Pharm. Bull., 49, 1110—1119 (2001).
31) Uchida M., Komatsu M., Morita S., Kanbe T., Yamasaki K., Nakagawa
K., Chem. Pharm. Bull., 37, 958—961 (1989).
32) Steven J. W., Org. Prep. Proced. Int., 26, 499—531 (1994).
33) Hrabalek A., Myznikov L., Kunes J., Vavrova K., Koldobskii G., Tetra-
hedron Lett., 45, 7955—7957 (2004).
15) Tekiner-Gulbas B., Temiz-Arpaci O., Yildiz I., Aki-Sener E., Yalcin I.,
SAR QSAR Environ. Res., 17, 121—132 (2006).
16) Lage H., Aki-Sener E., Yalcin I., Int. J. Cancer, 119, 213—220 (2006).
17) White A. W., Curtin N. J., Eastman B. W., Golding B. T., Hostomsky
Z., Kyle S., Li J., Maegley K. A., Skalitzky D. J., Webber S. E., Yu X.
H., Griffin R. J., Bioorg. Med. Chem. Lett., 14, 2433—2437 (2004).
18) Bywater W. G., Coleman W. R., Kamm O., Merritt H. H., J. Am.
Chem. Soc., 67, 905 (1945).
19) Yamato M., J. Pharm. Soc. Jpn., 112, 81—89 (1992).
20) Nakano H., Inoue T., Kawasaki N., Miyataka H., Matsumoto H.,
Taguchi T., Inagaki N., Nagai H., Satoh T., Bioorg. Med. Chem., 8,
373—380 (2000).
21) Kocí J., Klimesová V., Waisser K., Kaustová J., Dahse H.-M.,
Möllmann U., Bioorg. Med. Chem. Lett., 12, 3275—3278 (2002).
22) Garuti L., Roberti M., Pizzirani D., Pession A., Leoncini E., Cenci V.,
Hrelia S., Farmaco, 59, 663—668 (2004).
23) Songx V., Lorenzi P. L. Drach Jc., Townsend L. B., Amidon G. L., J.
Med. Chem., 48, 1274—1277 (2005).
24) Novelli F., Tasso B., Sparatore F., Sparatore A., Farmaco, 52, 499—
507 (1997).
25) Akbay A., Oren I., Temiz-Arpaci O., Aki-Sener E., Yalçin I., Arzneim.-
Forsch., 53, 266—271 (2003).
26) Plemper R. K., Erlandson K. J., Lakdawala A. S., Sun A., Prussia A.,
Boonsombat J., Aki-Sener E., Yalcin I., Yildiz I., Temiz-Arpaci O.,
Tekiner B. P., Liotta D. C., Snyder J. P., Compans R. W., Proc. Natl.
34) Muraglia E., Kinzel O. D., Laufer R., Miller M. D., Moyer G., Munshi
V., Orvieto F., Palumbi M. C., Pescatore G., Rowley M., Williams P.
D., Summa V., Bioorg. Med. Chem. Lett., 16, 2748—2752 (2006).
35) Thevelein J., Van Dijck P., WO 01/16357 A2 (2001).
36) Shaw-reid C. A., Miller M., Hazuda D. J., Ferrer M., Sur S. M.,
Summa V., Lyle T. A., Kinzel O., Pescatore G., WO 2005/115147 A2
(2005).
37) Welz R., Müller S., Tetrahedron Lett., 43, 795—797 (2002).
38) Nematollahi D., Tammari E., J. Org. Chem., 70, 7769—7772 (2005).
39) Khodaei M. M., Alizadeh A., Pakravan N., J. Org. Chem., 73, 2527—
2532 (2008).
40) Baron E. J., Finegold S. M., “Bailey and Scott’s Diagnostic Microbiol-
ogy,” 8th ed., C.V. Mosby, St. Louis, 1990, pp. 184—188.
41) Andrews J. M., J. Antimicrob. Chemother., 48 (Suppl. 1), 5—16
(2001).
42) Blois M. S., Nature (London), 181, 1199—1200 (1958).
43) Oyaizu M., Jpn. J. Nutr., 44, 307—315 (1986).