Synthesis, in silico Study and Antimicrobial Evaluation of New Selenoglycolicamides

Article abstract of DOI:10.21577/0103-5053.20180148

Nine new compounds derived from selenoglycolic acid were synthesized, and their structures were fully characterized by elemental analysis, infrared (IR),¹H and¹³C nuclear magnetic resonance (NMR). The compounds were evaluated in an i

Full text of DOI:10.21577/0103-5053.20180148

http://dx.doi.org/10.21577/0103-5053.20180148
J. Braz. Chem. Soc., Vol. 00, No. 00, 1-10, 2018
Short Report
Printed in Brazil - ©2018 Sociedade Brasileira de Química
Synthesis, in silico Study and Antimicrobial Evaluation of New Selenoglycolicamides
Helivaldo D. S. Souza,a Roxana P. F. de Sousa,a Bruno F. Lira,a Raquel F. Vilela,a
Nathalie H. P. B. Borges,b José P. de Siqueira‑Junior,b Edeltrudes O. Lima,c
Jeane U. G. Jardim,c Gracielle A. T. da Silva,c José M. Barbosa‑Filhoc and
Petrônio F. de Athayde‑Filho*,a
aDepartamento de Química, Universidade Federal da Paraíba, 58051-900 João Pessoa-PB, Brazil
bDepartamento de Biologia Molecular, Universidade Federal da Paraíba,
58051-970 João Pessoa-PB, Brazil
cDepartamento de Ciências Farmacêuticas, Universidade Federal da Paraíba,
58051-900 João Pessoa-PB, Brazil
Nine new compounds derived from selenoglycolic acid were synthesized, and their structures
1
were fully characterized by elemental analysis, infrared (IR), H and 13C nuclear magnetic
resonance (NMR). The compounds were evaluated in an in silico study and showed strong to
moderate antibacterial activity against several strains of Staphylococcus aureus. In particular, three
compounds exhibited excellent antibacterial activity, with minimum inhibitory concentrations
(MICs) between 16 and 64 μg mL-1. Furthermore, two of the nine compounds showed antifungal
activity, with MIC of 1024 and 512 μg mL-1. In silico studies of the parameters of Lipinski’s rule
of five indicate that these compounds have potential to be new drug candidates.
Keywords: selenoglycolic acid, selenoglycolicamides, antibacterial activity, antifungal activity
Introduction
are specific transporters that export tetracyclines and
macrolides, respectively, and NorA is the most studied
and was the first described multidrug and toxin extrusion
protein in S. aureus,4,5 which confers resistance to a
wide range of compounds, including fluoroquinolones,
ethidium bromide, acriflavine, ammonium compounds,
chlorhexidine, dequalinium and others.6
The active efflux of drugs confers a moderate level
of resistance, causing an increase of up to 64 times the
minimum inhibitory concentration (MIC) at the expense
of increased expression of efflux pumps7 or through
synergism with other forms of resistance.8,9 Due to this,
it has shown promise for improving the effectiveness of
antimicrobial agents and its combination with efflux pump
inhibitors (EPIs), which, besides expanding the usefulness
of existing antibiotics, reduces the emergence of resistant
mutant strains.10,11
Thetreatmentofbacteriaandfungihasbecomeagrowing
problem that concerns clinicians, the pharmaceutical
industry and chemists, due to increased resistance to the
available medicines in the market. These micro-organisms,
when they become multidrug resistant, are one of the major
causes of the increased mortality of the global population.1
Antibiotics shut down or subvert essential bacterial
functions. The resistance mechanisms appear to exploit
every possible strategy of preventing a drug from hitting
its target. The major types of clinically relevant resistance
mechanisms have been studied for a long time. The efflux
phenomenon, found in many species of bacteria, fungi
and mammalian cells, is shown to occur through default
accumulation within cells and is responsible for exporting
drugs from cells over the action of proteins, resulting in
low intracellular drug concentrations.2
One group of compounds that has been highlighted
in the scientific community, both in the synthesis and
the development of new therapeutic agents, is composed
of organoselenium compounds. These compounds are
obtained from reactions with elemental selenium12 and
electrophilic13,14 or nucleophilic15 reagents (inorganics
Many of these proteins are associated with treatment
failure in nosocomial- and community-acquired infections
by Staphylococcus aureus.3 For example, TetK and MsrA
*e-mail: athayde-filho@quimica.ufpb.br

2
Synthesis, in silico Study and Antimicrobial Evaluation of New Selenoglycolicamides
J. Braz. Chem. Soc.
or organics) containing selenium. The organoselenium
compounds reported in the literature are presented as
biologically active molecules with antibacterial,15-17
antifungal,18-21 anti-inflammatory,22 antinociceptive,22
antiparasitic23-25 and antiviral activities.26,27
Considering the potential of organoselenium compounds
in the synthesis of new pharmaceutical drug candidates, a
series of nine selenoglycolicamides were planned for
evaluating an in silico study as new structures of drug
candidates, obeying the Lipinski’s rules. The compounds
were synthesized using our selenoglycolic acid synthesis
protocol, and these are the early studies of microbiological
activity against bacteria (Staphylococcus aureus) and fungi
(Candida albicans and Candida tropicalis).
selenoglycolicamides (7a-i) with a yield of 70-80% by an
aroylselenide (6) reaction with α-chloro-N-arylacetamides
(2a-i). The purity of the compounds was checked by
examining the melting ranges.
The selenoglycolicamide structures were confirmed
1
using infrared (IR), H and 13C nuclear magnetic
resonance (NMR) spectroscopic techniques. The principal
characteristic of the IR spectra is the C=O stretch. All
of the compounds (7a-i) presented two C=O functional
group absorptions at 1651-1670 cm-1, corresponding
to (–NH)‑C=O, and at 1670-1674 cm-1, corresponding
to (–Se)–C=O. For all compounds, the N–H stretch of the
amide groups was approximately 3270 cm-1. Specifically,
for compounds 7b and 7i, the nitro group was characterized
by two absorption bands in the ranges of 1529-1510 cm-1
1
Results and Discussion
and 1362-1342 cm-1, respectively. In the H NMR
spectra for all compounds (7a-i), two α-hydrogen atoms
(methylene group) had chemical shifts (d) as singlets in
the range of d 3.77-4.01 ppm. The hydrogen atoms of the
amide group had chemical shifts as singlets in the range
of d 8.24-10.91 ppm. The hydrogen atoms of the attached
benzene ring had d between 6.5 and 8.40 ppm. In the 7c
spectra, the ethyl group was characterized by a triplet at
d 1.19 ppm representing the three hydrogen atoms and
by a quartet at d 2.59 ppm for two secondary hydrogen.
In the 7d spectra, the methyl group was characterized
by a singlet at d 2.29 ppm for three primary hydrogens.
Specifically, for the 7g compound, the isopropyl group was
characterized by a doublet at d 1.21 ppm representing the
six hydrogen atoms and by a septet at d 2.68 ppm for the
tertiary hydrogen. In the 7h spectra, the methoxy group was
characterized by a singlet at d 3.77 ppm. For the 13C NMR
spectra, the carbon from the C=O corresponding to the
Chemistry
The synthesis of the compounds derived from
selenoglycolic acid used our previously described
procedures28 with few modifications. The
selenoglycolicamides (7a-i) were obtained in four synthetic
steps, as described in Scheme 1.
The first stage produces α-chloro-N-arylacetamides
(2a-i) by N-acetylation reaction with arylamines (1a-i)
and 2-chloroacetyl chloride, in triethylamine and CH2Cl2
as solvent.29 The second to fourth stages are a one-pot
synthesis. The second stage produces sodium hydrogen
selenide (4) by the powdered gray selenium (3) reaction
with sodium borohydride in aqueous solution. In the
third stage, NaHSe react with aroyl chlorides, forming
sodium aroylselenides (6). The fourth stage produces
Scheme 1. Synthetic route for the synthesis of the target molecules. Reagents and conditions: (i) Et3N, CH2Cl2, 0-rt (room temperature), 20 h, 95-85%;
(ii) NaBH4, H2O, rt; (iii) H2O, rt, 1 h; (iv) H2O, rt, 70-80%.

Vol. 00, No. 00, 2018
Souza et al.
3
selenol ester group was characterized by d between 193.0
and 197.6 ppm, and the C=O corresponding to the amide
group was characterized by d between 167 and 168 ppm.
The α-carbon was characterized by d between 28.0 and
29.0 ppm, and all d attributed to aromatic carbons were
characterized by peaks between 117.0 and 156.5 ppm. In
the spectra of the compound 7c, two additional signals in
the aliphatic region at d 28.3 and 15.7 ppm, attributed to
carbons of the ethyl group, were observed. In the spectra
of the compound 7d, an additional signal in the aliphatic
region at d 21.0 ppm for the carbon of the methyl group
was observed. In the 7g spectra, two additional signals
at d 33.7 and 24.1 ppm, attributed to the carbons of the
isopropyl group, were observed. In the 7h spectra, an
additional signal at d 55.6 ppm attributed to the carbon
of the methoxy group was observed.
Prior analysis of these parameters drastically reduces
the necessary time for the pharmacokinetic study in the
clinical phase. Many studies relating physico-chemical
standards with ADME parameters were performed in the
90s. The most widespread study was from the pioneer
Lipinski et al.,32 which presented a relationship between
pharmacokinetics and physico-chemical parameters,
indicating that a molecule will have high potential as
drug if it highly resembles existing drugs, a phenomenon
known as drug-likeness; the study established standards
named “Rules of 5” by Lipinski, which consider only
four factors (whose values are multiples of five): molar
mass ≤ 500 g mol-1, log P ≤ 5, number of hydrogen bond
acceptors ≤ 10 (accounted in function of N or O atoms in
the molecule), and number of hydrogen bond donors ≤ 5
(accounted in function of NH or OH groups in the
molecule).
In silico study
In this work, an in silico study of selenoglycolicamides
7a-i was performed to verify the Lipinski parameters using
OSIRIS Property Explorer,33 Molinspiration34 and Swiss
ADME35 software. The topological polar surface area
(TPSA), absorption percentage (%ABS), drug-likeness
and drug score were included in this study. The absorption
percentage was calculated according to Zhao et al.,36 and is
expressed by the equation %ABS = 109 – (0.345 × TPSA).
The calculated values for the studies are shown in Table 1.
According to the results obtained from the in silico
approach, all of the compounds obeyed the Rules of 5
by Lipinski, thus indicating a good oral bioavailability
during drug administration. The obtained TPSA values
for all compounds were below 140 Å2, indicating a great
permeability of the compound in the cellular plasma
membrane. The absorption percentage showed a great
absorption of the compounds, as the lowest absorptions
for the compounds 7b and 7i were 77.26%, and the best
The process of new drug development requires a great
deal of time and resources. The theoretical studies have a
fundamental role to minimize these factors because they
show indications of potential drug applications. Several
authors mention that it is not enough for a compound to
present high biological activity and low toxicity to be
tested as a drug; it is also necessary to meet the ADME
pharmacokinetics parameters (absorption, distribution,
metabolism and excretion), which determine the access and
the concentration of the compound in the therapeutic target
and its subsequent elimination by the organism.30,31 Many
drug candidates can be discarded for presenting unfavorable
pharmacokinetics. The ADME parameters can be verified
by in silico studies based on calculated physico-chemical
standards. These standards emphasize lipophilicity, water
solubility, molecule size and flexibility.
Table 1. In silico study of the selenoglycolicamide compounds
Lipinski parameter
Compound
Drug
likeness
Drug
score
TPSA / Å2 %ABS / %
log S
Class
MW
HBD
HBA
milog P
3.23
3.19
4.14
3.68
4.04
3.91
4.74
3.29
3.80
nV
0
7a
7b
7c
7d
7e
7f
318.23
363.23
346.28
332.26
397.13
352.67
360.31
348.26
397.67
1
1
1
1
1
1
1
1
1
3
6
3
3
3
3
3
4
6
46.17
91.99
46.17
46.17
46.17
46.17
46.17
55.40
91.99
93.07
77.26
93.07
93.07
93.07
93.07
93.07
89.88
77.26
–3.53
–3.57
–4.16
–3.82
–4.43
–4.12
–4.37
–3.59
–4.16
soluble
soluble
–4.23
–17.9
–2.69
–3.88
–4.48
–1.39
–4.84
–3.6
0.25
0.23
0.19
0.24
0.20
0.26
0.20
0.25
0.19
0
0
moderately
soluble
0
0
moderately
moderately
moderately
soluble
0
7g
7h
7i
0
0
0
moderately –11.56
Physicochemical properties: MW: molecular weight; HBD: hydrogen bonding donor; HBA: hydrogen bonding acceptor; milog P: octanol/water partition
coefficient based on Molinspiration milog P model; nV: number of violations; TPSA: total polar surface area; %ABS: adsorption percentage; log S: coefficient
of solubility determined by the ESOL method calculated on SwissADME; Class: insoluble < –10 < poor < –6 < moderately < –4 < soluble < –2 < very <
0 < highly.

4
Synthesis, in silico Study and Antimicrobial Evaluation of New Selenoglycolicamides
J. Braz. Chem. Soc.
absorption for the compounds 7a, 7c, 7d, 7e, 7f and 7g was
93.08 %, as shown in Table 1.
below 10 μg mL-1 (ideal ≤ 2 μg mL-1) are considered of great
interest to pharmaceutical industries. However, according to
Radhakrishna et al.,38 ester derivatives from selenoglycolic
acids and their analogues, are considered moderate
to good active agents against Staphylococcus aureus
bacteria with MIC values between 0.1-50 mg mL-1 and the
organoselenium compounds from ebselen derivatives are
considered highly active against Staphylococcus aureus
with MIC values between 2.0-32 μg mL-1.39
The log S (coefficient of solubility determined by
the ESOL method calculated on SwissADME) of many
commercial drugs shows a value greater than –4.00. As
shown in Table 1, the log S presented values in the range
of –4.43 to –3.53 for compounds 7a-i. From these results,
7a, 7b, 7d and 7h compounds are considered soluble, while
7c, 7e, 7f, 7g and 7i are considered moderately soluble.
The drug-likeness evaluates the comparison of the
investigated compounds through fragments and/or physical
properties similar to those of the most known drugs, and
they must present positive values. The obtained values in this
study are in the range of –17.9 and –1.39. The drug score
value combines the records of drug-likeness, lipophilicity,
solubility, molecular mass and toxicity risks into a single
numerical value, which varies from 0.0 to 1.0 and can be
used to predict the global potential of one compound as a new
drug candidate. The obtained values from this approach were
between 0.12 and 0.26, suggesting that these compounds
have potential to become new drug candidates.
In general, for the efflux strains tested, of the nine
compounds 7a-i, only three compounds (7a, 7f and 7i)
were more effective, presenting MIC values ≤ 64 μg mL-1,
while the other selenoglycolicamides presented MIC
values between 256-128 μg mL-1, considered low inhibitory
activity. The 7a compound presented activity against the
strains IS-58 and RN-4220 with an MIC of 32 μg mL-1 and
in the strain SA-1199B with an MIC of 128 μg mL-1. The
7f compound presented activity against the strain IS-58,
with an MIC of 16 μg mL-1, and the strains RN-4220 and
SA-1199B, with an MIC of 32 μg mL-1. The 7i compound
presented an MIC of 32 μg mL-1 for the strain IS-58,
64 μg mL-1 for the strain RN-4220 and 16 μg mL-1 for
the strain SA-1199B. Thus, the compounds 7a, 7f and 7i
were shown to be better than the standard compound used
in the experiment, chloramphenicol. On the other hand,
the compounds 7b and 7h presented identical activities
against the strains IS-58 and RN-4220, with an MIC of
128 μg mL-1. The compounds 7c, 7d and 7e presented an
MIC of 256 μg mL-1 against three efflux species (IS-58,
RN-4220 and SA-1199B). In the ATCC 25923 strain, the
compounds showed low activity, with the exception of
compound 7a, which presented activity results identical
to chloramphenicol.
Biological study
Antibacterial activity
The selenoglycolicamides 7a, 7f and 7i showed relevant
antibacterial activity (MIC ≤ 64 μg mL-1) against the strains
Staphylococcus aureus IS-58, RN-4220 and SA-1199B,
which over-express the effluent pumps TetK, MsrA
and NorA, respectively. The other selenoglycolicamide
compounds showed MIC values between 128-256 μg mL-1,
considered low inhibitory activity (Table 2).
According to Gibbons,37 compounds (from natural
products) with MIC above 100 μg mL-1 are considered
poorly active antimicrobial agents, while those with MIC
According to Zloh and co-workers,40,41 a characteristic
of substances that possess a high degree of lipophilicity is
Table 2. Minimum inhibitory concentrations (MIC) of selenoglycolicamides against strains of S. aureus
Minimum inhibitory concentration / (μg mL-1)
Selenoglycolicamide
Strains (efflux pump)
ATCC 25923
128
IS-58 (TetK)
RN-4220 (MsrA)
SA-1199B (NorA)
7a
32
128
256
256
256
16
32
128
256
256
256
32
128
256
256
256
256
32
7b
256
7c
> 256
> 256
> 256
> 256
> 256
256
7d
7e
7f
7g
128
128
32
256
128
64
256
256
16
7h
7i
> 256
128
Cloramphenicol
64
64
64
TetK: tetracycline efflux protein; MsrA: macrolides efflux protein; NorA: fluoroquinolone efflux protein.

Vol. 00, No. 00, 2018
Souza et al.
5
the ability to inhibit the multidrug-resistant bacteria (MRB)
that have efflux proteins as a defense mechanism. This study
showed that the obtained results were not consistent with
the Zloh and co-workers40,41 affirmation, i.e., this rule does
not apply to glycolic amides. The compounds 7g, 7c and
7e showed the highest lipophilicity values, and they should
demonstrate antimicrobial action results consistent with
the Zloh co-workers40,41 affirmation; however, they were
not the most active strains tested. The compounds with
halogens in their structure can increase lipophilicity, as
was shown by the compounds 7f and 7i, both with chlorine,
which presented better results against the strains IS-58
(TetK), RN-4220 (MsrA) and SA-1199B (NorA). However,
compound 7e, with bromine, did not show significant
antibacterial activity. Although compound 7b possessed a
nitro group, which is a pharmacophoric group capable of
promoting an increase in the hydrophobic character of the
molecule,42,43 it did not show antibacterial activity. However,
the 7i compound, which contains a chlorine atom and a nitro
group, demonstrated a relevant antibacterial effect. For the
compounds 7c, 7d, 7g and 7h that possess activating groups
on the benzene ring, effective antimicrobial action against
the tested strains was not observed.
microorganisms. The antimicrobial activity of the products
was interpreted and considered as active or inactive based
on the following criteria: 50-500 μg mL-1 = strong/great
activity; 600-1500 μg mL-1 = moderate activity; and above
1500 μg mL-1 = weak activity or inactive product.
Of the nine compounds tested, compounds 7b-7g did not
exhibit inhibitory activity against the strains mentioned in
the evaluation. The 7a compound demonstrated an inhibition
of 100% and a moderate activity against the four strains
of Candida (C. albicans ATCC-76485, C. albicans LM-5,
C. tropicalis ATCC-13803 and C. tropicalis LM-96), at an
MIC of 1024 μg mL-1. However, the 7i compound presented
an inhibition of 50% with a great activity against two of
the four strains of Candida (C. tropicalis ATCC-13803 and
C. tropicalis LM-96), with an MIC of 512 μg mL-1. The
results (Table 3), therefore, were considered between good
and moderate in terms of biological activity and taking into
consideration the established parameters.44
Conclusions
In this short report, we performed an in silico study of
selenoglycolicamides 7a-i, all of which obeyed the Rules
of 5 by Lipinski, thus indicating a good oral bioavailability
during drug administration and a desirable profile as new
drug candidates. Based on our in silico study, we synthesized
nine novel selenoglycolicamides and characterized them
using IR, 1H and 13C NMR spectroscopic techniques. All
compounds were evaluated in vitro against different fungi
and bacteria. In the antifungal activity study, only two of
the nine compounds showed inhibition against the strains;
the 7a compound demonstrated inhibition against the fungi
of the genus Candida albicans and Candida tropicalis, with
Antifungal activity
The in vitro antifungal activity of compounds 7a-i was
evaluated by the microdilution method with four strains
of pathogenic fungi, Candida albicans (ATCC-76485 and
LM-5) and Candida tropicalis (ATCC-13803 and LM-96),
using nystatin as the standard drug. The compounds
were tested at concentrations of 64 to 1024 μg mL-1 and
solubilized in dimethyl sulfoxide (DMSO, Merck), in
a proportion up to 10% to avoid interference with the
Table 3. Minimum inhibitory concentrations (MIC) of the selenoglycolicamides against strains of Candida
Minimum inhibitory concentration / (μg mL-1)
Candida strains
Compound
C. albicans
C. albicans
C. tropicalis
C. tropicalis
ATCC-76485
LM-5
ATCC-13803
LM-96
7a
1024
+
1024
+
1024
+
1024
+
7b
7c
+
+
+
+
7d
+
+
+
+
7e
+
+
+
+
7f
+
+
+
+
7g
+
+
+
+
7h
+
+
+
+
7i
+
+
512
+
512
+
Yeast control
+
+
Control of culture medium
Nystatin
–
–
–
–
–
–
–
–
–: there was no growth of the microorganism; +: growth of the microorganism.

6
Synthesis, in silico Study and Antimicrobial Evaluation of New Selenoglycolicamides
J. Braz. Chem. Soc.
an MIC of 1024 μg mL-1, and the 7i compound presented an
inhibition against the fungi of the genus Candida tropicalis,
with an MIC of 512 μg mL-1. In the antibacterial activity
study, of the nine compounds, only 7a, 7f and 7i presented
satisfactory antibacterial activity, with an MIC ≤ 64 μg mL-1,
being more potent than the standard drug chloramphenicol.
Future studies will involve syntheses of new derivatives to
carry out studies of the substances as antibiotic-resistant
bacterial resistance modulators.
α-Chloro-N-phenylacetamide (2a)
1
Yield: 93%, mp 133-135 °C; H NMR (200 MHz,
CDCl3) d 4.16 (s, 2H, CH2), 7.15 (t, 1H, H-Ar), 7.33 (t,
2H, H-Ar), 7.52 (d, 2H, H-Ar), 8.28 (s, 1H, NH); 13C NMR
(50 MHz, CDCl3) d 164.0, 136.77, 129.2, 125.35, 120.27,
43.00; IR (KBr) ν / cm-1 3267, 3205, 3143 (NH), 3098,
3049 (CHAr.), 2947, 2862 (CHAlip.), 1672 (C=O), 1604,
1496 (C=CAr.), 1290, 1250 (C–Cl), 1078, 858 (CHAr.), 750
(NH), 557, 499 (C–CAr.).
Experimental
α-Chloro-N-(p-nitrophenyl)acetamide (2b)
1
Yield: 85%, mp 188-190 °C; H NMR (200 MHz,
Chemistry
DMSO-d6) d 4.36 (s, 2H, CH2), 7.85 (d, 2H, H-Ar), 8.26
(d, 2H, Ar-H), 10.93 (s, 1H, NH); 13C NMR (50 MHz,
DMSO-d6) d 165.6, 144.6, 142.6, 125.07, 119.1, 43.6; IR
(KBr) ν / cm-1 3277, 3227, 3163 (NH), 3109, 3070 (CHAr.),
2939, 2825 (CHAlip), 1688 (C=O), 1624, 1506 (C=CAr.), 1597,
1570, 1338 (NO2), 1294, 1255 (C–Cl), 1172, 869, 850 (C–N
of ArNO2), 1111, 829 (CHAr.), 748 (NH), 526 (C–CAr.).
All used reagents and solvents were purchased from
commercial sources (Sigma-Aldrich) and used without
further purification. The progress of the reactions was
monitored by thin layer chromatography (TLC) on
silica gel plates. The purification of the compounds was
performed by recrystallization in ethanol and confirmed by
determining the melting range on an MQAPF-302 hotplate
(Microquímica). The structures of the new compounds
7a-j were confirmed by elemental analysis on Carlo Erba
EA1110 elemental analyzer. The IR spectra were obtained
on a Shimadzu model IR Prestige-21 FTIR spectrometer
using KBr pellets. 1H and 13C NMR spectra were obtained
on two different machines: a Varian 200 NMR (200 MHz
for 1H and 50 MHz for 13C) andVarian 500 NMR (500 MHz
α-Chloro-N-(p-ethylphenyl)acetamide (2c)
1
Yield: 92%, mp 140-142 °C; H NMR (200 MHz,
CDCl3) d 1.22 (t, 3H, CH3), 2.63 (q, 2H, CH2), 4.17 (s, 2H,
CH2), 7.18 (d, 2H, H-Ar), 7.44 (d, 2H, H-Ar), 8.23 (s, 1H,
.
.
NH); 13C NMR (50 MHz, DMSO-d6) d 163.89, 141.53,
134.37, 128.56, 120.45, 43.0, 28.45, 15.7; IR (KBr) ν / cm-1
3308, 3273, 3201 (NH), 3088, 2965 (CHAr.), 2964, 2868
(CHAlip.), 1668 (C=O), 1614, 1512 (C=CAr.), 1292, 1254
(C–Cl), 1118, 864 (CHAr.), 740 (NH), 540, 487 (C–CAr.).
1
for H and 126 MHz for 13C). Deuterated chloroform
(CDCl3) and deuterated dimethyl sulfoxide (DMSO-d6)
were used as solvent, and tetramethylsilane (TMS) was
used for the internal standard. Chemical shifts (d) were
measured in parts per million (ppm), and the coupling
constants (J), in hertz (Hz).
α-Chloro-N-(p-methylphenyl)acetamide (2d)
Yield: 95%, mp 182-184 °C; 1H NMR (200 MHz, CDCl3)
d 2.33 (s, 3H, CH3), 4.17 (s, 2H, CH2), 7.15 (d, 2H, H-Ar),
7.42 (d, 2H, H-Ar), 8.21 (s, 1H, NH); 13C NMR (50 MHz,
DMSO-d6) d 163.86, 135.1, 134.2, 129.7, 120.3, 42.66, 21.0;
IR (KBr) ν/ cm-1 3307, 3273, 3203 (NH), 3134, 3089 (CHAr.),
2953 (CHAlip.), 1674 (C=O), 1616, 1552 (C=CAr.), 1292, 1252
(C–Cl), 114, 864 (CHAr.), 748 (NH), 505 (C–CAr.).
General procedure for the preparation of α-chloro-
N-arylacetamide (2a-i)29
To the mixture of substituted aromatic amine (0.020 mol)
and Et3N (0.024 mol), solubilized in 20 mL of CH2Cl2
at a temperature of 0 °C, maintained by an ice bath,
2-chloroacetyl chloride (0.024 mol) was slowly added. The
ice bath was then removed, and the reaction stayed under
agitation for 6 h at room temperature. The reaction mixture
was monitored by TLC (hexane/methyl acetate 1:1).At the
end of reaction, the reaction mixture was concentrated at
reduced pressure and cold water was added to the reaction
mixture, causing the formation of a solid. The solid was
then filtered and washed with cold water (3 × 20 mL), and
the final product was purified by recrystallization with an
ethanol/water (1:1) mixture.
α-Chloro-N-(p-bromophenyl)acetamide (2e)
1
Yield: 85%, mp 184-186 °C; H NMR (200 MHz,
DMSO-d6) d 4.27 (s, 2H, CH2), 7.55 (m, 4H, H-Ar), 10.45
(s, 1H, NH); 13C NMR (50 MHz, DMSO-d6) d 164.8,
137.8, 131.7, 121.28, 115.5, 43.56; IR (KBr) ν / cm-1 3263,
3194 (NH), 3124, 3076 (CHAr.), 2999, 2953 (CHAlip.), 1670
(C=O), 1610, 1550 (C=CAr.), 1281, 1246 (C–Cl), 1188
(C–Br), 1072, 860 (CHAr.), 736 (NH), 497 (C–CAr.).
α-Chloro-N-(p-chlorophenyl)acetamide (2f)
1
Yield: 79%, mp 170-172 °C; H NMR (200 MHz,
DMSO-d6) d 4.27 (s, 2H, CH2), 7.40 (d, 2H, H-Ar), 7.63

Vol. 00, No. 00, 2018
Souza et al.
7
(d, 2H, H-Ar), 10.45 (s, 1H, NH); 13C NMR (50 MHz,
DMSO-d6) d 164.8, 137.4, 128.8, 127.4, 120.9, 43.5; IR
(KBr) ν / cm-1 3264, 3198 (NH), 3128, 3080 (CHAr.), 3003,
2951 (CHAlip.), 1668 (C=O), 1612, 1551 (C=CAr.), 1281,
1246 (C–Cl), 1095 (C–Cl of ArCl), 1010, 862 (CHAr.), 737
(NH), 567, 501 (C–CAr.).
room temperature. Then, the reaction mixture was subjected
to extraction with dichloromethane (3 × 25 mL). The
organic phase was filtered on a porcelain plate containing
silica gel and then concentrated under reduced pressure,
providing the final products that were recrystallized in
ethanol.
α-Chloro-N-(p-isopropylphenyl)acetamide (2g)
N-Phenylbenzoselenoglycolicamide (7a)
1
1
Yield: 77%, mp 141-143 °C; H NMR (200 MHz,
Yield: 75%, white solid, mp 132-133 °C; H NMR
DMSO-d6) d 1.24 (d, 6H, CH3), 2.90 (s, 1H, CH), 4.17 (s,
2H, CH2), 7.23 (d, 2H, H-Ar), 7.45 (d, 2H, H-Ar), 8.21 (s,
1H, NH); 13C NMR (50 MHz, DMSO-d6) d 163.87, 146.19,
134.4, 127.16, 120.47, 43.0, 33.76, 24.1; IR (KBr) ν / cm-1
3271, 3199 (NH), 3130 (CHAr.), 2960, 2870 (CHAlip.), 1674
(C=O), 1612, 1548 (C=CAr.), 1282, 1250 (C–Cl), 1300,
1282 (iCHAlip.), 1016, 837 (CHAr.), 779 (NH), 534 (C–CAr.).
(200 MHz, CDCl3) d 8.36 (s, 1H, NH), 7.92 (d, J 7.4 Hz,
2H, H-3 and H-3’), 7.65 (t, J 7.3 Hz, 1H, H-5), 7.54-7.45
(m, 4H, H-4, H-4’, H-9 and H-13), 7.30 (t, J 7.3 Hz, 2H,
H-10 and H-12), 7.08 (t, J 7.3 Hz, 1H, H-11), 3.78 (s, 2H,
H-6); 13C NMR (50 MHz, CDCl3) d 196.74 (C-1), 137.94
(C-2), 129.16 (C-3 and C-3’), 129.09 (C-4 and C-4’),
134.73 (C-5), 28.27 (C-6), 168.25 (C-7), 138.06 (C-8),
119.91 (C-9 and C-13), 127.38 (C-10 and C-12), 124.44
(C-11); IR (KBr) ν / cm-1 3292 (N–H), 3053 (=C–H, Ar),
1654 (–N–CO), 1674 (–Se–CO), 1596 and 1444 (C=C,Ar).
Anal. calcd. for C15H13NO2Se: C, 56.61; H, 4.12; N, 4.40;
found: C, 55.30; H, 3.90; N, 4.84.
α-Chloro-N-(p-methoxyphenyl)acetamide (2h)
1
Yield: 85%, mp 119-120 °C; H NMR (200 MHz,
DMSO-d6) d 3.79 (s, 3H, OCH3), 4.17 (s, 2H, CH2), 6.88 (d,
2H, H-Ar), 7.43 (d, 2H, H-Ar), 8.20 (s, 1H, NH); 13C NMR
(50 MHz, DMSO-d6) d 163.89, 157.16, 129.79, 122.2,
114.3, 55.6, 42.97; IR (KBr) ν / cm-1 3296, 3199 (NH),
3136, 3072 (CHAr.), 2956, 2835 (CHAlip.), 1666 (C=O), 1605,
1548 (C=CAr.), 1346, 1301 (C–Cl), 1248, 1113 (C–O–C),
1029, 831 (CHAr.), 788 (NH), 582, 532 (C–CAr.).
N-(4-Nitrophenyl)benzoselenoglycolicamide (7b)
1
Yield: 70%, white solid, mp 192-193 °C; H NMR
(200 MHz, CDCl3) d 8.82 (s, 1H, NH), 8.19 (d, J 9.2 Hz,
2H, H-10 and H-12), 7.94 (d, J 7.1 Hz, 2H, H-3 and
H-3’), 7.73-7.66 (m, 3H, H-5 to H-9 and H-13), 7.52
(t, J 7.5 Hz, 2H, H-4 and H-4’), 3.80 (s, H, 2H, H-6);
13C NMR (50 MHz, CDCl3) d 197.59 (C-1), 137.66 (C-2),
129.38 (C-3 and C-3’), 127.7 (C-4 and C-4’), 135.16
(C-5), 28.02 (C-6), 168.83 (C-7), 143.91 (C-8), 119.22
(C-9 and C-13), 125.2 (C-10 and C-12), 143.66 (C-11);
IR (KBr) ν / cm-1 3261 (N–H), 3207-3067 (=C–H, Ar),
1670 (–Se‑CO and –N–CO overlapping), 1564 and 1404
(C=C, Ar), 1510 and 1342 (NO2), 852 (=C–H, Ar). Anal.
calcd. for C15H12N2O4Se: C, 49.60; H, 3.33; N, 7.71; found:
C, 48.68; H, 3.19; N, 7.99.
α-Chloro-N-(m-nitro-p-chlorophenyl)acetamide (2i)
1
Yield: 80%, mp 120-122 °C; H NMR (200 MHz,
DMSO-d6) d 4.32 (s, 2H, CH2), 7.74 (d, 1H, H-Ar), 7.81
(dd, 1H, H-Ar), 8.40 (d, 1H, H-Ar), 10.87 (s, 1H, NH);
13C NMR (50 MHz, DMSO-d6) d 165.5, 147.28, 138.3,
132.2, 124.27, 119.16, 115.76, 43.4; IR (KBr) ν / cm-1 3313,
3269 (NH), 3122, 3094 (CHAr.), 2945, 2881 (CHAlip.), 1691
(C=O), 1605, 1544 (C=CAr.), 1483, 1404, 1344 (NO2), 1300,
1265 (C–Cl), 1045, 831 (CHAr.), 895 (C–N ofArNO2), 785
(NH), 559 (C–CAr.).
Generalprocedureforthepreparationselenoglycolicamides28
N-(4-Ethylphenyl)benzoselenoglycolicamide (7c)
1
Yield: 72%, white solid, mp 124-125 °C; H NMR
Sodium borohydride (0.0139 mol) was dissolved
in 6 mL of water and added, slowly, under a selenium
suspension (0.0063 mol) in 6 mL of water, contained in
a flask of 50 mL. The reaction was exothermic, and a
liberation of hydrogen gas was observed. Then (in situ),
the aroyl chloride (0.0063 mol) was added, slowly, at a
temperature of 30 °C. After 60 min of agitation at room
temperature, α-chloro-N-arylacetamides (0.0063 mol)
in a small quantity of acetone were added, slowly, to the
solution. The formation of a precipitate was observed at the
end of reaction. The mixture was agitated for another 2 h at
(200 MHz, CDCl3) d 8.30 (s, 1H, NH), 7.91 (d, J 7.6 Hz,
2H, H-3 and H-3’), 7.63 (t, J 7.4 Hz, 1H, H-5), 7.52-7.66
(m, 4H, H-4, H-4’, H-9 and H-13), 7.12 (d, J 8.4 Hz, 2H,
H-10 and H-12), 3.78 (s, 2H, H-6), 2.59 (q, 2H, CH2CH3),
1.19 (t, 3H, CH2CH3); 13C NMR (50 MHz, CDCl3) d 196.62
(C-1), 137.98 (C-2), 129.21 (C-3 and C-3’), 128.37 (C-4
and C-4’), 134.69 (C-5), 28.27 (C-6), 168.11 (C-7), 135.67
(C-8), 120.04 (C-9 and C-13), 127.55 (C-10 and C-12),
140.58 (C-11), 28.43 (CH2), 15.83 (CH3); IR (KBr) ν / cm-1
3284 (N–H), 3068 (=C–H, Ar), 1674 (–Se–CO), 1651
(–N–CO), 1593 and 1413 (C=C, Ar), 883 (=C–H, Ar), 767

8
Synthesis, in silico Study and Antimicrobial Evaluation of New Selenoglycolicamides
J. Braz. Chem. Soc.
(N–H). Anal. calcd. for C17H17NO2Se: C, 58.96; H, 4.95;
N, 4.04; found: C, 59.78; H, 4.95; N, 4.90.
(200 MHz, CDCl3) d 8.25 (s, 1H, NH), 7.92 (d, J 7.5 Hz,
2H, H-3 and H-3’), 7.64 (t, J 7.4 Hz, 1H, H-5), 7.49 (t,
J 7.8 Hz, 2H, H-4 and H-4’), 7.43 (d, J 8.4 Hz, 2H, H-9 and
H-13), 7.16 (d, J 8.4 Hz, 2H, H-10 and H-12), 3.77 (s, 2H,
H-6), 2.86 (sep, 1H, CH(CH3)2), 1.21 (d, 6H, CH(CH3)2);
13C NMR (50 MHz, CDCl3) d 196.63 (C-1), 138.07 (C-2),
129.23 (C-3 and C-3’), 127.58 (C-4 and C-4’), 134.7
(C-5), 28.29 (C-6), 168.1 (C-7), 135.78 (C-8), 120.1 (C-9
and C-13), 126.96 (C-10 and C-12), 145.26 (C-11), 33.74
(CH(CH3)2), 24.1 (CH(CH3)2); IR (KBr) ν / cm-1 3282
(N–H), 3124-3061 (=C–H, Ar), 1674 (–Se–CO), 1656
(–N–CO), 1600-1446 (C=C, Ar), 889 (=C–H, Ar), 767
(N–H). Anal. calcd. for C18H19NO2Se: C, 60.00; H, 5.32;
N, 3.98; found: C, 60.76; H, 5.48; N, 4.55.
N-(4-Methylphenyl)benzoselenoglycolicamide (7d)
1
Yield: 77%, white solid, mp 132-134 °C; H NMR
(200 MHz, CDCl3) d 8.28 (s, 1H, NH), 7.92 (d, J 7.6 Hz,
2H, H-3 and H-3’), 7.65 (t, J 7.4 Hz, 1H, H-5), 7.49 (t,
J 7.4 Hz, 2H, H-4 and H-4’), 7.40 (d, J 8.4 Hz, 2H, H-9
and H-13), 7.10 (d, J 8.4 Hz, 2H, H-10 and H-12), 3.77 (s,
2H, H-6), 2.29 (s, 3H, CH3); 13C NMR (50 MHz, CDCl3)
d 196.64 (C-1), 135.49 (C-2), 129.54 (C-3 and C-3’),
129.22 (C-4 and C-4’), 134.7 (C-5), 28.27 (C-6), 168.1
(C-7), 134.09 (C-8), 119.95 (C-9 and C-13), 127.56 (C-10
and C-12), 137.99 (C-11), 20.99 (CH3); IR (KBr) ν / cm-1
3269.34 (N–H), 3037.89 (=C–H,Ar), 1674 (–Se–CO), 1651
(–N–CO), 1595 and 1402 (C=C,Ar), 889 (=C–H,Ar).Anal.
calcd. for C16H15NO2Se: C, 57.84; H, 4.55; N, 4.22; found:
C, 58.37; H, 4.52; N, 5.01.
N-(4-Methoxyphenyl)benzoselenoglycolicamide (7h)
1
Yield: 75%, white solid, mp 139-140 °C; H NMR
(200 MHz, CDCl3) d 8.24 (s, 1H, NH), 7.92 (d, J 7.1 Hz,
2H, H-3 and H-3’), 7.65 (t, J 7.1 Hz, 1H, H-5), 7.53-7.49
(m, 4H, H-4, H-4’, H-9 and H-13), 6.48 (d, J 9.0 Hz, 2H,
H-10 and H-12), 3.77 (s, 5H, H-6 and OCH3); 13C NMR
(50 MHz, CDCl3) d 196.37 (C-1), 138.03 (C-2), 129.19
(C-3 and C-3’), 127.53 (C-4 and C-4’), 134.63 (C-5), 29.22
(C-6), 168.0 (C-7), 131.19 (C-8), 121.74 (C-9 and C-13),
114.22 (C-10 and C-12), 156.58 (C-11), 55.57 (OCH3);
IR (KBr) ν / cm-1 3282 (N–H), 3124-3061 (=C–H, Ar),
1678 (–Se–CO), 1639 (–N–CO), 1541 (C=C, Ar), 1029
(C–O–C), 883 (=C–H, Ar), 767 (N–H). Anal. calcd. for
C16H15NO3Se: C, 55.18; H, 4.34; N, 4.02; found: C, 54.33;
H, 4.25; N, 4.44.
N-(4-Bromophenyl)benzoselenoglycolicamide (7e)
1
Yield: 73%, white solid, mp 165-167 °C; H NMR
(200 MHz, CDCl3) d 8.40 (s, 1H, NH), 7.92 (d, J 7.6 Hz,
2H, H-3 and H-3’), 7.67 (t, J 6.9 Hz, 1H, H-5), 7.50 (t,
J 7.5 Hz, 2H, H-4 and H-4’), 7.42 (s, 4H, H-9, H-10, H-12
and H-13), 3.77 (s, 2H, H-6); 13C NMR (50 MHz, CDCl3)
d 197.03 (C-1), 137.15 (C-2), 129.28 (C-3 and C-3’),
127.62 (C-4 and C-4’), 134.9 (C-5), 28.14 (C-6), 168.35
(C-7), 137.83 (C-8), 121.41 (C-9 and C-13), 132.02 (C-10
and C-12), 117.0 (C-11); IR (KBr) ν / cm-1 3263 (N–H),
3182-3059 (=C–H, Ar), 1672 (–Se–CO), 1651 (–N–CO),
1537 and 1487 (C=C, Ar), 815 (=C–H, Ar). Anal. calcd.
for C15H12BrNO2Se: C, 45.37; H, 3.05; N, 3.53; found: C,
46.08; H, 3.03; N, 4.05.
N-(4-Chloro-3-nitrophenyl)benzoselenoglycolicamide (7i)
1
Yield: 72%, gray solid, mp 132-134 °C; H NMR
(200 MHz, CDCl3) d 10.91 (s, 1H, NH), 8.40 (d, J 2.2 Hz,
1H, H-9), 7.90 (d, J 7.1 Hz, 2H, H-3 and H-3’), 7.74 (m,
3H, H-5, H-12 and H-13), 7.58 (t, J 7.5 Hz, 2H, H-4 and
H-4’), 4.01 (s, 2H, H-6); 13C NMR (50 MHz, CDCl3)
d 193.09 (C-1), 138.77 (C-2), 129.46 (C-3 and C-3’),
126.92 (C-4 and C-4’), 134.59 (C-5), 29.02 (C-6), 167.9
(C-7), 137.58 (C-8), 115.43 (C-9), 147.26 (C-10), 118.71
(C-11), 123.97 (C-12), 132.10 (C-13); IR (KBr) ν / cm-1
3238 (N–H), 3101-3059 (=C–H,Ar), 1674 (–Se–CO), 1654
(–N–CO), 1595 and 1408 (C=C,Ar), 1529 and 1361 (NO2),
1047 (C–Cl), 835 (=C–H, Ar), 765 (N–H). Anal. calcd.
for C15H11ClN2O4Se: C, 45.30; H, 2.79; N, 7.04; found: C,
45.80; H, 2.79; N, 7.47.
N-(4-Chlorophenyl)benzoselenoglycolicamide (7f)
1
Yield: 68%, white solid, mp 152-154 °C; H NMR
(200 MHz, CDCl3) d 8.38 (s, 1H, NH), 7.92 (d, J 7.9 Hz,
2H, H-3 and H-3’), 7.66 (t, J 7.4 Hz, 1H, H-5), 7.51-7.49
(m, 4H, H-4, H-4’, H-9 and H-13), 7.26 (d, 2H, J 8.4 Hz,
H-10 and H-12), 3.77 (s, 2H, H-6); 13C NMR (50 MHz,
CDCl3) d 196.92 (C-1), 137.93 (C-2), 129.29 (C-3 and
C-3’), 129.08 (C-4 and C-4’), 134.86 (C-5), 28.15 (C-6),
168.28 (C-7), 136.7 (C-8), 121.12 (C-9 and C-13), 127.62
(C-10 and C-12), 129.42 (C-11); IR (KBr) ν / cm-1 3278
(N–H), 3122-3068 (=C–H, Ar), 1674 (–Se–CO), 1654
(–N–CO), 1544 and 1400 (C=C, Ar), 833 (=C–H, Ar).
Anal. calcd. for C15H12ClNO2Se: C, 51.08; H, 3.48; N, 3.97;
found: C, 51.98; H, 3.43; N, 4.10.
Biological activity
N-(4-Isopropylphenyl)benzoselenoglycolicamide (7g)
Antibacterial activity
1
Yield: 70%, white solid, mp 108-110 °C; H NMR
Organoselenium compounds were screened in vitro for

Vol. 00, No. 00, 2018
Souza et al.
9
antibacterial activity and antimicrobial modulatory effects
in three effluxing strains: SA-1199B, which carries the
gene encoding the NorA fluoroquinolone efflux protein;5,45
RN-4220, which has the pUL5054 plasmid that carries the
gene encoding the protein MsrA for macrolide efflux;46 and
IS-58, which has the efflux protein for tetracycline (TetK).47
It was also used a standard strainATCC 25923, an important
strain for the quality test disk diffusion and MIC testing
Staphylococcus spp., which does not produce beta-lactamase.
All of these strains were cultured on nutrient agar slants
(blood agar base (BAB), Difco Laboratories). Before being
used, the cells were grown in nutrient broth infusion (brain
heart infusion (BHI), Difco Laboratories) for 18-24 h at
37 °C. These strains were provided by Dr Simon Gibbons
(University of London). The MICs of organoselenium
compounds were determined by microdilution assay using
a suspension of ca. 105 colony forming unit (CFU) mL-1 and
drug concentration range of 512-4 μg mL-1. MIC is defined
as the lowest concentration at which no growth is observed.48
The results of antibacterial activity are presented in Table 2.
drug nystatin (100 μg mL-1). The plates were incubated at
37 °C for 24-48 h. For each strain, the MIC was defined as
the minimum concentration capable of inhibiting the fungal
growth, by visual observation of the wells, when compared
to the control. All of the tests were performed in duplicate,
and the results were expressed as the geometric average of
the MIC values obtained in the two assays. The antifungal
activity results are presented in Table 3.
Supplementary Information
Supplementary information is available free of charge
at http://jbcs.sbq.org.br as PDF file.
Acknowledgments
This work was supported by the following Brazilian
agencies: CNPq and CAPES.
References
Antifungal activity
1. Oliveira, C. S.; Lira. B. F.; Barbosa-Filho, J. M.; Lorenzo, J. G.
F.; Menezes, C. P.; Santos, J. M. C. G.; Lima, E. O.; Athayde-
Filho, P. F.; J. Braz. Chem. Soc. 2013, 24, 115.
2. Kourtesi, C.; Ball, A. R.; Huang, Y. Y.; Jachak, S. M.; Vera, D.
M. A.; Khondkar, P.; Gibbons, S.; Hamblin M. R.; Tegos G. P.;
Open Microbiol. J. 2013, 7, 34.
In the antifungal assay of the synthesized compounds,
the microorganisms used were Candida albicans
(ATCC-76485 and LM-5) and Candida tropicalis
(ATCC-13803 and LM-96). They were acquired at the
Micoteca of the Mycology Laboratory, Department of
Pharmaceutical Sciences (DCF), Health Sciences Center
(CCS) at Federal University of Paraíba, Brazil. The
fungus strains were maintained in appropriate medium,
agar Sabouraud dextrose (ASD, Difco Laboratories), and
stored at 4 and 35 °C. The microorganism suspension
was prepared according with the 0.5 McFarland scale
tube and was adjusted by the use of a spectrophotometer
(Leitz-Phtometer 340-800) to 90% T (530 nm),
corresponding to approximately 106 CFU mL-1.49-51 The
antifungal tests were performed in Sabouraud dextrose
broth (SDB, Difco Laboratories), which was prepared and
used according the manufacturer’s instructions. The MIC
value was determined by the microdilution method using
96-well microtiter plates with “U” bottoms and in duplicate.
To each plate well, 100 μL of SDB was added in double
concentrated liquid medium. Then, 100 μL of the product
solution (also double concentrated) was distributed in the
wells of the first line of the plate. Using serial dilution
(proportion of two), concentrations of 1024 to 64 µg mL-1
were obtained so that the higher concentrations were in the
first line of the plate and the lower concentrations were in
the last. Finally, 10 μL of inoculum was added to the wells,
where each column of the plate referred to a specific strain.
The same was done in the culture medium with the fungal
3. Gibbons, S.; Oluwatuyi, M.; Kaatz, G. W.; J. Antimicrob.
Chemother. 2003, 51, 13.
4. Gibbons, S.; Moser, E.; Kaatz, G. W.; Planta Med. 2004, 70,
1240.
5. Kaatz, G. W.; Seo, S. M.; Antimicrob. Agents Chemother. 1995,
39, 2650.
6. Hassan, K.A.; Skurray, R.A.; Brown, M. H.; J. Mol. Microbiol.
Biotechnol. 2007, 12, 180.
7. Broskey, J.; Coleman, K.; Gwynn, M. N.; Mccloskey, L.; Traini,
C.; Voelker, L.; Warren, R.; J. Antimicrob. Chemother. 2000,
45, 95.
8. Mazzariol, A.; Tokue, Y.; Kanegawa, T. M.; Cornalia, G.;
Nikaido, H.; Antimicrob. Agents Chemother. 2000, 44, 3441.
9. Payne, D. J.; Gwynn, M. N.; Holmes, D. J.; Pompliano, D. L.;
Nat. Rev. Drug Discovery 2007, 6, 29.
10. Fernebro, J.; Drug Resist. Updates 2011, 14, 125.
11. Lynch, A. S.; Biochem. Pharmacol. 2006, 71, 949.
12. Santos, E. A.; Hamel, E.; Bai, R.; Burnett, J. C.; Tozatti, C. S.
S.; Bogo, D.; Perdomo, R. T.; Antunes, A. M. M.; Marques,
M. M.; Matos, M. F. C.; Lima, D. P.; Bioorg. Med. Chem. Lett.
2013, 23, 4669.
13. Wilkins, L. C.; Günter, B. A. R.; Walther, M.; Lawson, J. R.;
Wirth, T.; Melen, R. L.; Angew. Chem., Int. Ed. 2016, 55,
11292.

10
Synthesis, in silico Study and Antimicrobial Evaluation of New Selenoglycolicamides
J. Braz. Chem. Soc.
14. Parker, W. R.; Brodbelt, J. S.; J. Am. Soc. Mass Spectrom. 2016,
32. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J.;
Adv. Drug Delivery Rev. 1997, 23, 3.
27, 1344.
15. Radhakrishna, P. M.; Sharadamma, K. C.; Vagdevi, H. M.;
Abhilekha, P. M.; Rubeena, M. S.; Nischal, K.; Int. J. Chem.
2010, 2, 149.
33. http://www.organic-chemistry.org/prog/peo/, accessed on
February 01, 2018.
34. http://www.molinspiration.com/, accessed on February 01,
2018.
16. Refat, M. S.; Abdel-Hafez, S. H.; Russ. J. Gen. Chem. 2016,
86, 1151.
35. http://www.swissadme.ch/, accessed on February 01, 2018.
36. Zhao, M. Y.; Abraham, M. H.; Le, J.; Hersey, A.; Luscombe,
C. N.; Beck, G.; Sherborne, B.; Pharm. Res. 2002, 19, 1446.
37. Gibbons, S.; Planta Med. 2008, 74, 594.
17. Deutch, C. E.; Spahija, I.; Wagner, C. E.; J. Appl. Microbiol.
2014, 117, 1487.
18. Abdel-Hafez, S. H.; Phosphorus, Sulfur Silicon Relat. Elem.
2010, 185, 37.
38. Radhakrishna, P. M.; Sharadamma, K. C.; Abhilekha, P. M.;
Rubeena Mubeen, S.; Nischal, K.; Int. J. Chem. 2010, 2, 149.
39. Piętka-Ottlik, M.;Wójtowicz-Mᴌochowska, H.; Koᴌodziejczyk,
K.; Piasecki, E.; Mᴌochowski, J.; Chem. Pharm. Bull. 2008, 56,
1423.
19. Kumar, S.; Sharma, N.; Maurya, I. K.; Bhasin, A. K. K.;
Wangoo, N.; Brandão, P.; Félix, V.; Bhasin, K. K.; Sharma, R.
K.; Eur. J. Med. Chem. 2016, 123, 916.
20. Kumar, S.; Sharma, N.; Maurya, I. K.; Verma, A.; Kumar, S.;
Bhasin, K. K.; Sharma, R. K.; New J. Chem. 2017, 41, 2919.
21. Rosseti, I. B.; Wagner, C.; Fachinetto, R.; Taube Junior, P.;
Costa, M. S.; Mycoses 2010, 54, 506.
40. Drakulić, B. J.; Juranić, I. O.; Erić, S.; Zloh, M.; Int. J. Pharm.
2008, 363, 40.
41. Zloh, M.; Kaatz, G. W.; Gibbons, S.; Bioorg Med. Chem. Lett.
2004, 14, 881.
22. Chagas, P. M.; Rosa, S. G.; Sari, M. H. M.; Oliveira, C. E. S.;
Canto, R. F. S.; Luz, S. C. A.; Braga, A. L.; Nogueira, C. W.;
Pharmacol., Biochem. Behav. 2014, 118, 87.
42. Korolkovas, A.; Burckhalter, J. H.; Química Farmacêutica,
2a ed.; Guanabara Koogan: Rio de Janeiro, 1988.
43. Barreiro, E. J.; Fraga, C. A. M.; Química Medicinal: as Bases
Moleculares da Ação dos Fármacos, 3a ed.; Artmed: Porto
Alegre, 2014.
23. Baquedano, Y.; Alcolea, V.; Toro, M. A.; Gutiérrez, K. J.;
Nguewa, P.; Font, M.; Moreno, E.; Espuela, S.; Jiménez-Ruiz,
A.; Palop, J. A.; Plano, D.; Sanmartin, C.; Antimicrob. Agents
Chemother. 2016, 60, 3802.
44. Holetz, F. B.; Howes, M. J.; Lee, C. C.; Steventon, G.; Mem.
Inst. Oswaldo Cruz 2002, 97, 1027.
24. Fernández-Rubio, C.; Campbell, D.; Vacas, A.; Ibañez, E.;
Moreno, E.; Espuelas, S.; Calvo, A.; Palop, J. A.; Plano, D.;
Sanmartin, C.; Nguewa, P. A.; Antimicrob. Agents Chemother.
2015, 59, 5705.
45. Kaatz, G. W.; Seo, S. M.; Ruble, C. A.; Antimicrob. Agents
Chemother. 1993, 37, 1086.
46. Ross, J. I.; Farrell, A. M.; Eady, E. A.; Cove, J. H.; Cunliffe, W.
J.; J Antimicrob. Chemother. 1989, 24, 851.
25. Martín-Montes,Á.; Plano, D.; Martín-Escolano, R.;Alcolea,V.;
Díaz, M.; Pérez-Silanes, S.; Espuelas, S.; Moreno, E.; Marín,
C.; Gutiérrez-Sánchez, R.; Sanmartin, C.; Sánchez-Moreno,
M.; Antimicrob. Agents Chemother. 2017, 61, 2546.
26. Sahu, P. K.; Umme, T.; Yu, J.; Nayak, A.; Kim, G.; Noh, M.;
Jae-Young, L.; Kim, D. D.; Jeong, L. S.; J. Med. Chem. 2015,
58, 8734.
47. Gibbons, S.; Udo, E. E.; Phytother Res. 2000, 14, 139.
48. Clinical and Laboratory Standards Institute (CLSI); Document
M100-S17, M7-A6: Performance Standards for Antimicrobial
Susceptibility Testing; Approved Standard, 6th ed.; CLSI:Wayne,
PA, 2003.
49. National Committee for Clinical and Laboratory Standards
(NCCLS); Performance Standards for Antimicrobial Disk
Susceptibility Tests, 7th ed.; NCCLS: Villanova, 2000.
50. Hadacek, F.; Greger, H.; Phytochem. Anal. 2000, 11, 137.
51. Cleeland, R.; Squires, E. In Evaluation of New Antimicrobials
in vitro and in Experimental Animal Infections; Lorian, V., ed.;
Antibiotics in Laboratory Medicine, Lippincott Williams &
Wilkins: Baltimore, 1991, p. 739.
27. Pietka-Ottlik, M.; Potaczek, P.; Piasecki, E.; Mlochowski, J.;
Molecules 2010, 15, 8214.
28. Athayde-Filho, P. F.; Souza, A. G.; Morais, S. A.; Botelho, J. R.;
Barbosa-Filho, J. M.; Miller, J.; Lira, B. F.; Arkivoc 2004, 6, 22.
29. Ma, L.; Li, S.; Zheng, H.; Chen, J.; Lin, L.; Ye, X.; Chen, Z.;
Xu, Q.; Chen, T.; Yang, J.; Qiu, N.; Wang, G.; Peng, A.; Ding,
Y.; Wei, Y.; Chen, L.; Eur. J. Med. Chem. 2011, 46, 2003.
30. Veber, D. F.; Johnson, S. R.; Cheng, H. U.; Smith, B. R.; Ward,
K. W.; Kopple, K. D.; J. Med. Chem. 2002, 45, 2615.
31. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J.;
Adv. Drug Delivery Rev. 2001, 46, 3.
Submitted: May 21, 2018
Published online: August 6, 2018
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