Antimicrobial effects of 1-monocaprylin and 1-monocaproin through in vitro growth inhibition and molecular docking studies

Article abstract of DOI:10.3844/ajbbsp.2017.123.131

1-monocaproin and 1-monocaprylin synthesized through a novel process by the chemical reaction of glycidol and their respective fatty acids with copper acetate as the catalyst possessed the amphiphilic property. 1- monoacyl glycerols synthesized were found to exhibit antibacterial, antifungal, anti parasitic and antiviral properties. 1-monocaproin and 1- monocaprylin were able to show their antibacterial effect by inhibiting the growth of the Gram negative bacteria Escherichia coli, Pseudomonas aeruginosa and Gram positive bacteria Staphylococcus aureus, Bacillus subtilis at concentrations of 100-500 ppm. The Minimal Inhibitory Concentration (MIC) of both 1-monoacyl glycerols were found to be 0.5 ppm. 1-monocaproin and 1-monocaprylin were able to show their antifungal effect by inhibiting the growth of the filamentous fungi Mucor racemosus and Rhizopus stolonifer at the concentration of 1000 ppm. Based on the molecular interaction and common binding interaction study, 1- monocaproin is expected to exhibit a similar antiviral activity as that of Oseltamivir to H5N1 influenza virus hemagglutinin. 1-monocaprylin and 1- monocaproin synthesized using copper acetate could exhibit a broad spectrum antimicrobial effect in combination with other monoacyl glycerols or with other antimicrobial agents.

Full text of DOI:10.3844/ajbbsp.2017.123.131

mistry and Biotechnology
Journal of Biochemistry and Biotechnology
Original Research Paper
Antimicrobial Effects of 1-Monocaprylin and 1-Monocaproin
Through in vitro Growth Inhibition and Molecular Docking
Studies
1
2
Palaniappan Maheswari and Kasthuri Revathi
1
Department of Biotechnology, Science and Humanities, Sathyabama University,
Jeppiaar Nagar, Rajiv Gandhi Road, Chennai - 600 119, India
2
Department of Zoology, Ethiraj College for Women, Egmore, Chennai- 600 008, India
Article history
Abstract: 1-monocaproin and 1-monocaprylin synthesized through a novel
process by the chemical reaction of glycidol and their respective fatty acids
with copper acetate as the catalyst possessed the amphiphilic property. 1-
monoacyl glycerols synthesized were found to exhibit antibacterial,
antifungal, anti parasitic and antiviral properties. 1-monocaproin and 1-
monocaprylin were able to show their antibacterial effect by inhibiting the
growth of the Gram negative bacteria Escherichia coli, Pseudomonas
aeruginosa and Gram positive bacteria Staphylococcus aureus, Bacillus
subtilis at concentrations of 100–500 ppm. The Minimal Inhibitory
Concentration (MIC) of both 1-monoacyl glycerols were found to be 0.5
ppm. 1-monocaproin and 1-monocaprylin were able to show their
antifungal effect by inhibiting the growth of the filamentous fungi Mucor
racemosus and Rhizopus stolonifer at the concentration of 1000 ppm. Based
on the molecular interaction and common binding interaction study, 1-
monocaproin is expected to exhibit a similar antiviral activity as that of
Oseltamivir to H N influenza virus hemagglutinin. 1-monocaprylin and 1-
Received: 16-06-2017
Revised: 19-07-2017
Accepted: 19-08-2017
Corresponding Author:
Palaniappan Maheswari,
Department of Biotechnology,
Science and Humanities,
Sathyabama University,
Jeppiaar Nagar, Rajiv Gandhi
Road, Chennai - 600 119, India
Phone: 044- 25504536
Email: maheswari.p1966@gmail.com
5
1
monocaproin synthesized using copper acetate could exhibit a broad
spectrum antimicrobial effect in combination with other monoacyl
glycerols or with other antimicrobial agents.
Keywords: Monoacyl Glycerols, 1-Monocaprylin, 1-Monocaproin,
Antimicrobial, Anti Bacterial, Antifungal, Antiviral
Hemagglutinin (HA) and Neuraminidase (NA) play a vital
role in the attachment and release of the Influenza A virus,
Introduction
Food-borne diseases caused by the microbial
contamination from bacteria, fungi, parasite and virus pose
major public health problems in developed and developing
countries (Altekruse et al., 1999). Food-borne infectious
diseases cause serious day to day problem for the health
care system and led to tremendous economic loss and hence
it is important to develop the means to control the
transmission from food to humans (Newell et al., 2010).
This is achieved by either limiting or preventing the growth
of undesirable microbial flora in food products
(Dolezalkova et al., 2012). More new efficient methods for
the decontamination or prevention of food contamination
by these pathogens would therefore be desirable. Among
the viral borne illness, avian influenza such as A (H N ) and
respectively (McNicholl and McNicholl, 2001; CDC,
2006; Lupiani and Reddy, 2009). Hemagglutinin (HA), the
glycoprotein in influenza virus envelope, plays a critical
role in viral binding, fusion and entry processes. Therefore,
HA is a promising target for developing anti-influenza
drugs, which block the initial entry step of viral life
cycle. Recently, molecular modeling and computational
chemistry based computer-aided drug design provided great
help for modern drug development (Marshall, 1987).
Software programs such as Auto Dock were widely used to
search potential inhibitor for protein targets (Morris, et al.,
2009). In this study, we employed the strategy of molecule
docking to explore 1-monocaproin comparing with
Oseltamivir as potential H N hemagglutinin inhibitors.
5
1
5
1
A (H N ) are the ones which caused serious infection in
7 9
Monoacyl glycerols (MAGs) are gaining more attention
as antimicrobial agents nowadays as they are generally
human beings. The two surface glycoprotein;
© 2017 Palaniappan Maheswari and Kasthuri Revathi. This open access article is distributed under a Creative Commons
Attribution (CC-BY) 3.0 license.

Palaniappan Maheswari and Kasthuri Revathi / Journal of Biochemistry and Biotechnology 2017, 13 (3): 123.131
DOI: 10.3844/ajabssp.2017.123.131
considered as non-harmful safe agents with no adverse
reactions and non- toxic to mucosa which makes them
suitable for wide industrial applications. MAGs exhibit
Monoacylglycerols (MAGs)
MAGs with C-06:0 and C-08:0 were prepared as per
Janis et al. (2000) published earlier but by a modified
procedure using copper acetate as the catalyst. Initially,
the catalysts were prepared by the reaction of
Cu(AcO) .H O with hexanoic acid and octanoic acid for
inhibitory
effects
against
major
food-borne
microorganisms due to their amphiphilic and
emulsifying properties (Jan et al., 2003). The precise
mode of the action against microorganisms is not yet
clear and postulated several hypotheses. One
hypothesis is based on the amphiphilic character of
MAG molecule which aids in their penetration and
incorporation into cytoplasmic membrane and
subsequently disrupts the cell permeability and prevents
the transportation of the nutrients (Nair et al., 2004;
Dufour et al., 2007). An alternative hypothesis
postulates the penetration of fatty acids and dissociated in
the inner cell environment, thereby increasing the intra-
cellular acidity (Sun et al., 1998). The physicochemical and
functional properties as well as antimicrobial activity of
MAGs depend on the number of carbon atoms and
double bonds present in the fatty acid chain
(Wang and Johnson, 1997). There are many studies
published recently for the monoacylglycerol with C-
10:0 and above showing the inhibitory effects on the
growth of microorganisms (Kabara et al., 1977;
Razavi-Rohani and Griffiths, 1994). Hence, MAGs
with C-6:0 and C-8:0 were chosen for our current
study with the objectives; (1) synthesis of 1-mono
caproin and 1-monocaprylin by a novel process
through the catalytic addition of respective fatty acids
to glycidol with copper acetate as the catalyst; (2)
evaluation of the inhibition property against selected
food borne bacteria and fungi through in vitro and
MIC studies and (3) evaluation of the antiviral
property of 1-monocaprion through the molecular
interaction study and common binding interaction
with crystal structure of H N influenza virus
2
2
the synthesis of 1- mono caproin and 1- mono caprylin
respectively with toluene as the reaction medium. 1-
mono caproin was prepared with 0.02 mol hexanoic acid
with 0.25g of catalyst prepared with hexanoic acid with
0.03 mol of glycidol and the yield was 65%. 1- mono
caprylin was prepared with 0.01 mol octanoic acid with
0.1g of catalyst prepared with octanoic acid with 0.015
mol of glycidol and the yield was 60%. Products were
purified for the removal of residual glycidol and to reduce
the quantity of copper ions from the catalyst through
column chromatography. MAGs were run through
Thin Layer Chromatography (TLC) to determine their
purity and confirmed by Nuclear Magnetic Resonance
spectroscopy (NMR) and ensured the residual copper
−1
ions to be <50 mg kg .
Assay of Antibacterial Activities
Bacterial strains were maintained on nutrient agar
until use. The antibacterial activity of 1-monocaprion
(HAP) and 1-monocaprylin (OAP) were screened using
agar well diffusion method (Jahangirian et al., 2013)
against the selected organism mentioned in section 2.1.1
along with control at concentrations of 100, 250 and
500ppm and the zone of inhibition was measured with
antibiotic zone scale in mm.
Minimum Inhibitory Concentration (MIC)
MIC of the compounds OAP and HAP were determined
by agar diffusion assay method (Jahangirian et al., 2013) at
four different concentrations (0.5, 1, 10 and 100ppm
each) against E. coli and S. aureus along with control
in duplicate samples.
5
1
hemagglutinin as drug target protein along with a
standard drug Oseltamivir.
Assay of Antifungal Activities
Materials and Methods
Details of Microorganisms
Bacterial Strains
1-monocaprion (HAP) and 1-monocaprylin (OAP)
were screened for antifungal activity (Serrano et al.,
2004) against the selected organism mentioned in section
2.1.2 at the concentration of 1000ppm along with control
with potato dextrose agar and the inhibition was
represented as percentage
Salmonella typhimurium (ATCC 23765), Bacillus
subtilis (ATCC 25912), E. coli (ATCC 25922),
Staphylococcus aureus (ATCC 25923), Pseudomonas
Preparation of Molecular Structure
aeruginosa
(ATCC
27853),
Sterptococcus
To perform the molecular docking between
hemagglutinin and potential inhibitors, we employed
the Crystal Structure of a H N avian influenza virus
pneumonia (ATCC 34501).
Fungal Strains
5
1
hemagglutinin of PDB: 2KF0. The chemsketch tools
were used to draw the ligands and converted in to
protein data bank format for the docking using the
chemical language format.
Aspergillus niger (ATCC 22342), Rhizopus oryzae
(ATCC 9363), Aspergillus flavus (ATCC 9643) and
Leucothrix mucor (ATCC 27891).
124

Palaniappan Maheswari and Kasthuri Revathi / Journal of Biochemistry and Biotechnology 2017, 13 (3): 123.131
DOI: 10.3844/ajabssp.2017.123.131
Molecular Docking
carbons, the lauric acid was found to possess more
inhibitory activity against Gram-positive bacteria
(Kabara et al., 1972) and MAG synthesized with caproic
acid and caprylic acid in our study were found to show
similar inhibitory effect.
In this study, we employed Auto Dock 4.02 v
software for the preparation of drug target protein, The
polar hydrogen's were added along with kollmann
charges and the respective drug target protein was saved
in current mode of protein data bank. Docking was
carried out with genetic algorithm mode with population
size of 150, with the maximum number of energy
evaluations of 2500000, maximum numbers of
generations being 27000 with 20 runs. The best run with
negative binding energy was considered as best results.
The interaction results were visualized using acclerys
discovery studio 4.5 visualizer. Using Auto Grid
program the interaction energies for the ligand, standard
drug and the drug target protein were calculated and
based on the above, the grid was placed in equal
dimensions 50×50×50 in XYZ dimensions with 0.4
spacing in angstroms along box is placed in -74.536 X,
12.015 Y, 33.301 Z directions respectively. Since the
active sites of hemagglutinin in H N were highly
In the earlier studies, E. coli and P. aeruginosa were
proved to be show resistance against monocaprin even at
−1
the concentration of 1,000 mg L . However, in our
studies, both 1-monocaproin and 1-monocaprylin were
found to be inhibitive at 0.5 ppm itself for these two
species and to the Gram negative bacteria
Staphylococcus aureus and Bacillus subtilis as shown in
Fig. 3. Similar inhibitory effects were observed in
monolaurin along with lactic acid on Staphylococcus
aureus on meat products (Kabara, 1985). Monocaprin
was found to increase the sensitivity of Bacillus
cereus spores in thermal inactivation (Chaibi et al.,
1998) and combined with monolaurin inhibited the
growth of Listeria monocytogenes (Nair et al., 2004).
Antifungal Effect
5
1
conserved, the docking pocket were compared with ten
key amino acid residues including PHE B:63, ALA
B:65, PHE B:88, LEU B:89, TRP B:92, GLY A:304,
GLY A:303, CYS A:305, PRO A:306 and TYR A:308
and compared with Oseltamivir and 1-monocaproin.
Similarly, the MAGs were tested against fungi;
Aspergillus niger, Rhizopus oryzae, Aspergillus flavus
and Leucothrix mucor. Antifungal effects of both tested
MAGs as % of inhibition are expressed in Table 3.
Monocaproin had shown 60% inhibition against
filamentous fungi, Mucor racemosus and Rhizopus
stolonifer whereas Monocaprylin had shown 80 and 65%
inhibition respectively. Both the MAGs were non
inhibitory to A. niger and A flavus.
Results and Discussion
Anti-Bacterial Effect
Mucormycosis, caused by Mucor species are the
second prevalent mucoralean fungus surpassing the
Antibacterial effects of both tested MAGs as Zone of
inhibition are arrayed in Table 2 and the Zone of
inhibition represented in Fig. 2. Out of the three Gram
negative bacteria tested, both 1-monocaproin (HAP) and
1-monocaprylin (OAP) were effective and shown
inhibition at a concentration of 100ppm itself for
Escherichia coli and Pseudomonas aeruginosa.
However, HAP and OAP were not inhibitive to
Salmonella typhimurium. Out of the three Gram
positive bacteria tested, both 1-monocaproin and 1-
monocaprylin were effective and shown inhibition at
100ppm itself for Staphylococcus aureus and Bacillus
subtilis. However, both the monoglycerides were not
inhibitive to Sterptococcus pneumonia.
Rhizopus
species
(Petrikkos
et
al.,
2012).
Monoglycerides had also found to prevent or inhibit the
growth of yeasts and filamentous fungi (Bergsson et al.,
1998; Bunkova et al., 2010; Ruzicka et al., 2003).
Monocaprin was found to be most efficient against all
tested Gram-positive bacteria, yeasts and filamentous
fungi except Mucor racemosus (Dolezalkova et al.,
2012; Bergsson et al., 2001) whereas our compound
monocaprylin showed good inhibition against Mucor
racemosus and Rhizopus stolonifer. Monolaurin had
shown the inhibition of spore at concentration of 0.5 mg
per ml for A niger and Penicillium (Rihakova et al.,
2001; Mansour et al., 1996) however, the compounds
tested in this study were non inhibitory.
There were lot published literatures to prove the
inhibitory property of various MAGs against Gram-
positive bacteria (Kabara et al., 1972; Schlievert et al.,
1992; Oh and Marshall, 1993; Branen and Davidson, 2004;
Bunkova et al., 2011) and the resistant property to Gram-
negative bacteria (Skrivanova et al., 2006; Kabara, 1978;
Kabara, 1984). Based on detailed published studies of
saturated fatty acids with chain lengths between 6 and 18
Antiviral Property
In this study, 1-monocaproin along with Oseltamivir
was employed for molecular docking with H N
5
1
hemagglutinin as shown in Fig. 1 in which the HA
0
glycoprotein of influenza virus is an integral
125

Palaniappan Maheswari and Kasthuri Revathi / Journal of Biochemistry and Biotechnology 2017, 13 (3): 123.131
DOI: 10.3844/ajabssp.2017.123.131
membrane
protein
(type
I
transmembrane
were presented Table 4. The minimum binding energy
and other properties revealed that the 1-monocaproin
and Oseltamivir could be successfully docked. The
estimated free energy of 1-monocaproin was - 4.39
kca/mol and Oseltamivir was -7.44 kca/mol. 1-
monocaproin showed almost 60% equivalent free
energy binding ability to HA when compared to
standard drug Oseltamivir. Table 5 shows the interaction
of the amino acids in the H N HA pocket and compared
glycoprotein) with approximate dimensions of 135 Å
(length) × 35-70 Å (radius). Each monomer of the HA
molecule consists of a globular head domain and a
stem domain. The globular domain consists of a part
of HA only (including the receptor-binding domain
1
and vestigial esterase domain), whereas the stem
domain contains parts of both HA and HA which
1
2
mediates the viral adsorption, membrane fusion, thus
realizing influenza virus entry. The potential inhibitor
property of 1-monocaproin was compared with
Oseltamivir. The general molecular properties of the
target test compounds Oseltamivir and 1-monocaproin
are detailed in Table 1. The conformation variations,
binding energies and inhibition constants for the
molecular docking of 1-monocaproin and Oseltamivir
5
1
with Oseltamivir and 1-monocaproin for its common
interaction. Oseltamivir standard drug showed
a
interaction with ten amino acids with the drug target
protein and 1-monocaproin showed interaction with five
amino acids. The amino acid residue; PHE B: 63, TYR A:
308, CYS A: 305 showed common binding interaction in
both compounds as represented in Fig. 4 and Table 5.
Table 1. Compound details
Structure
No of atoms Molecular composition
Molecular formula Molecular weight
13
C: 0.568, H: 0.095, O: 0.336
C H
9
O
4
190.243
18
1-Monocaproin
22
C: 0.603, H: 0.108, N: 0.088, O: 0.201 C H34 N O
16 2 4
318.462
Standard = Oseltamivir
Table 2. Antibacterial effects of monoacylglycerols MAG C-06:0 and MAG C–08:0
Zone of Inhibition (mm)
------------------------------------------------------------------------------------------
MAG C–06:0 - HAP MAG C-08:0 – OAP
------------------------------------------- ----------------------------------------------
Bacterial strain
Bacteria character
Gram-negative
Gram-negative
Gram-negative
500ppm
10
250ppm
11
100ppm
12
500ppm
250ppm
10
100ppm
11
Escherichia coli
8
Salmonella typhimurium
Pseudomonas aeruginosa
NI
NI
NI
NI
10
NI
NI
10
10.75
11
11.75
12.45
Staphylococcus aureus
Bacillus subtilis
Gram-positive
Gram-positive
Gram-positive
8
9
9
10
10
NI
10.25
10.5
NI
11
8
8.5
NI
9
10.5
NI
Sterptococcus pneumonia
NI
NI
Values represent the average of duplicate samples; NI -Not Inhibiting; HAP- Monocaproin; OAP - Monocaprylin
126

Palaniappan Maheswari and Kasthuri Revathi / Journal of Biochemistry and Biotechnology 2017, 13 (3): 123.131
DOI: 10.3844/ajabssp.2017.123.131
Table 3. Zone of Inhibition of monoacylglycerols MAG C-06:0 and MAG C-08:0 against filamentous fungi
% of inhibition
Microbial strain
Fungal character
MAG C-06:0 - HAP
MAG C–08:0 - OAP
Aspergillus flavus
Aspergillus niger
Mucor racemosus
Rhizopus stolonifer
Filamentous fungi
Filamentous fungi
Filamentous fungi
Filamentous fungi
NI
NI
60
60
NI
NI
80
65
Values represent the average of duplicate samples; HAP- Monocaproin; OAP – Monocaprylin; NI - Not Inhibiting
Table 4. The Energies of binding between H N HA and the targeted compounds 1-monocaproin and Oseltamivir
5 1
Parameters
1-monocaproin (Drug candidate)
Standard oseltamivir
Estimated inhibition constant, Ki
Estimated free energy of binding
Final intermolecular energy
vdW + Hbond + desolv energy
Electrostatic energy
98.61µm
3.52 µm
- 4.39 kca/mol
-6.77 kca/mol
-6.61 kca/mol
-0.17 kca/mol
-0.57 kca/mol
+2.39 kca/mol
-0.57 kca/mol
-7.44 kca/mol
-9.83 kca/mol
-9.78 kca/mol
-0.04 kca/mol
-1.11 kca/mol
+2.39 kca/mol
-1.11 kca/mol
Final total internal energy
Torsional free energy
Unbound system's energy
Table 5. Binding energy of the ligands to the active site/binding site hemagglutinin (H N ) drug target of the of avian influenza
5 1
Hemagglutinin (H N ) drug target
5 1
Aminoacid binding
distance in Å
1-Monocaproin
PHE B:63
HIS A:295
TYR A:308
THR A:301
CYS A:305
PHE B:63
ALA B:65
PHE B:88
LEU B:89
TRP B:92
1.97
4.41
5.26
2.48
3.51,2.18
4.21,2.16,2.18
3.55
Oseltamivir
4.79
4.85
2.76
GLY A:304
GLY A:303
CYS A:305
PRO A:306
TYR A:308
2.84
2.88
2.03
2.73
1.96
Note: A and B are chain in proteins
Fig. 1. Structural features of the influenza virus hemagglutinin. The picture shows α-helices and β-sheets of HA folded into a
0
compact monomer; an unfolded polypeptide chain of H N virus, which is composed of Heamagglutinin (HA) containing 3
5 1
different regions: (i) fusion (comprised of the N- and C-terminal regions of HA1 (F′ sub-domain) and HA (F sub-domain),
2
which are located in the stem domain, a main structure responsible for membrane fusion machinery), (ii) esterase (comprised
of two sub-domains between Fusion and receptor binding regions, which are located in the middle of folded HA and (iii)
receptor binding (almost in the middle of HA of unfolded HA and at the top of folded HA regions)
1
127

Palaniappan Maheswari and Kasthuri Revathi / Journal of Biochemistry and Biotechnology 2017, 13 (3): 123.131
DOI: 10.3844/ajabssp.2017.123.131
Fig. 2. Zone of inhibition. 1-monocaproin (HAP) and 1-monocaprylin (OAP) showing anti bacterial effect at a minimal dosage of
100 ppm against Gram negative bacteria Escherichia coli and Pseudomonas aeruginosa and gram positive bacteria
Staphylococcus aureus and Bacillus subtilis
Fig. 3. Minimum Inhibitory effect 1-monocaproin (HAP) and 1-monocaprylin (OAP) showing MIC at the concentration of 0.5 ppm
for Staphylococcus aureus and Bacillus subtilis
128

Palaniappan Maheswari and Kasthuri Revathi / Journal of Biochemistry and Biotechnology 2017, 13 (3): 123.131
DOI: 10.3844/ajabssp.2017.123.131
Fig. 4. Active site amino acid with 1-monocaproin and Oseltamivir; Binding interaction
Nowadays, two classes of anti-influenza drugs, M
exhibit similar inhibiting effect against H N
5 1
2
ion channel inhibitors and neuraminidase inhibitors
respectively, are used for prophylaxis and treatment of
influenza virus infection. Hemagglutinin (HA), the
glycoprotein in influenza virus envelope, plays a critical
role in viral binding, fusion and entry processes.
Therefore, HA is a promising target for developing anti-
influenza drugs, which block the initial entry step of
viral life cycle (Shen et al., 2013). Generally, AIV
including H N are sensitive to Oseltamivir and a small
hemagglutinin. Hence based on the molecular
interaction study and common binding interaction of
the compounds, the isolated compound 1-
monocaproin will also behave like Oseltamivir. The
previous study with homology modeling and docking
with 3D structure of the S-Adenosylmethionine
synthase a key enzyme in E. Maximum with 1-
monocaproin revealed that the synthesized 1-
monocaproin was found to possess anti parasite effect
as well (Maheswari and Revathi, 2016).
5
1
number of H N strains isolated from avian and human
5 1
origin have been reported to exhibit resistance to
Oseltamivir. Oral application of Oseltamivir via drinking
water reduced the morbidity, mortality, virus excretion
and chicken-to-chicken transmission in HPAIV H N
Conclusion
At present, the food industries employ MAGs
merely as emulsifying agents or stabilizers and it is
the right time that MAGs are considered most
significantly as antimicrobial agents. Since no single
MAGs exhibited a broad spectrum antimicrobial
effect, it can be concluded that a combination of
MAGs synthesized with C:06:0 to C:12:0 carbon
containing fatty acids may be considered as general-
purpose antimicrobials and preservatives as they
exhibit their inhibitory activity at very low
concentration itself and hence cost effective as well.
As 1-monocaproin docking with H N Hemagglutinin
5
2
experimentally infected chickens (WHO, 2012).
Oseltamivir was non-toxic for chicken embryos and
prevented the replication of an HPAIV H7N1 in
inoculated eggs (Allen et al., 2006). Since Oseltamivir
had shown strong interaction with the amino acids in the
active site of Hemagglutinin of H N virus, it is
5
1
considered to block the HA-mediated viral entry by
interfering with the receptor binding thereby cause the
cleavage of HA , followed by acidic pH-mediated
0
fusogenic rearrangement of HA and thereby prevent the
2
viral entry related factors. Since 60% similarities were
found in the estimated free energy and common binding
interaction with 3 amino acids between Oseltamivir and
1-monocaproin, 1-monocaproin is also expected to
5
1
of avian influenza virus showed Ki value of 98.61µm
is lesser than standard, 1-monocaproin could be a
potent antiviral agent against AV H N and perhaps
5
1
129

Palaniappan Maheswari and Kasthuri Revathi / Journal of Biochemistry and Biotechnology 2017, 13 (3): 123.131
DOI: 10.3844/ajabssp.2017.123.131
CDC, 2006. Centers for disease control and prevention:
High levels of adamantane resistance among influenza
A (H N ) viruses and interim guidelines for use of
could provide the similar effect as that of Oseltamivir
at higher dose. Hence the compounds synthesized for
this study; 1-monocaproin and 1-monocaprylin
remains promising for numerous applications and
need to be explored further.
3
2
antiviral agents-United States, 2005-06 influenza
season. MMWR Morb. Mortal, Wkly, 55: 44-46.
Chaibi, A., L.H. Ababouch M.R.Ghouila and F.F. Busta,
1998. Effect of monoglycerides on the thermal
inactivation kinetics of Bacillus cereus F4165/75
Acknowledgement
spores.
Food
Microbiol.,
15:
527-537.
We thank Bioneemtec India Private Limited, located
at Golden Jubilee Biotech Park for Women Society,
Chennai for their facility and support.
DOI: 10.1006/fmic.1998.0191
Dolezalkova, I., Z. Macalik, A. Butkovicova, R. Janis and
L. Bunkova, 2012. Monoacylglycerols as fruit juices
preservatives. Czech J. Food Sci., 30: 567-572.
Author’s Contributions
Dufour, M., J.M. Manson, P.J. Bremer, J.P. Dufour
and G.M. Cook et al., 2007. Characterization of
monolaurin resistance in Enterococcus faecalis.
Applied Environ. Microbiol., 73: 5507-5515.
Jahangirian, H., M.J. Haron, M.H.S. Ismail,
R. Rafiee-Moghaddam and L. Afsah-Hejri et al., 2013.
Well diffusion method for evaluation of antibacterial
activity of copper phenyl fatty hydroxamate
synthesized from canola and palm kernel oils. Digest J.
Nanomaterials Biostructures, 8: 1263-1270.
Palaniappan Maheswari: Designed the research
plan, participated in all experiments, coordinated the
data-analysis and writing the manuscript.
Kasthuri
Revathi:
Contributed
in
the
experimental design, organised for the study and
reviewed the manuscript.
Ethics
Jan, R., K. Velclova, R. Janis and J. Krejci, 2003.
Antimicrobial effects of 1-monoacylglycerols
prepared by catalytic reaction of glycidol with fatty
acids. Eur. Food Res. Technol., 217: 329-331.
DOI: 10.1002/jcc.21256
The authors declare that they have no competing
interests in this work.
References
Janis, R., J. Krejci and A. Klasek, 2000. Preparation of
1-monoacyIgIyceroIs from gIycidoI and fatty
acids cataIyzed by the chromium (III)-fatty acid
system. Eur. J. Lipid Sci. Technol., 102: 351-354.
Kabara, J.J., 1978. Structure-function relationships of
surfactants as antimicrobial agents. J. Society
Cosmetic Chem., 29: 733-741.
Altekruse, S.F., N.J. Stern, P.I. Fields and D.L. Swerdlow,
1999. Campylobacter jejuni--an emerging foodborne
pathogen. Emerging Infect. Dis., 5: 28-35.
DOI: 10.3201/eid0501.990104
Bergsson, G., J. Arnfinnsson O. Steingrimsson and
H. Thormar, 2001. Killing of gram-positive cocci by
fatty acids and monoglycerides. APMIS, 109:
670-678. DOI: 10.1034/j.1600-0463.2001.d01-131.x
Bergsson, G., J. Arnfinnsson, S.M. Karlsson,
O. Steingrimsson and H. Thormar, 1998. In vitro
inactivation of Chlamydia trachomatis by fatty acids
Kabara, J.J., 1985. Inhibition of Staphylococcus Aureus in a
Model Sausage System by Monoglycerides. In: The
Pharmacological Effect of Lipids II, Kabara, J.J. (Ed.),
Amer Oil Chemists Society, ISBN-10: 0935315020,
pp: 74-76.
and
monoglycerides.
Antimicrobial
Agents
Kabara, J.J., D.M. Swieczkowski A.J. Conley and J.P.
Truant, 1972. Fatty acids and derivatives as
antimicrobial agents. Antimicrob. Agents Chemother.,
2: 23-28. DOI: 10.1128/AAC.2.1.23
Chemotherapy, 42: 2290-2294.
Branen, J. and P.M. Davidson, 2004. Enhancement of
nisin, lysozyme and monolaurin antimicrobial
activities by ethylenediaminetetraacetic acid and
lactoferrin. Int. J. Food Microbio., 90: 63-74.
DOI: 10.1016/S0168-1605(03)00172-7
Kabara, J.J., R. Vrable and M.L.K Jie, 1977.
Antimicrobial lipids: Natural and synthetic fatty
acids and monoglycerides. Lipids, 12: 753-759.
Kabara, J.J., 1984. Antimicrobial agents derived from
fatty acids. J. Am. Oil Chem. Soc., 61: 397-403.
DOI: 10.1007/BF02678802
Bunkova, L., F. Bunka R. Janis J. Krejci and
I. Dolezalkov, et al., 2011. Comparison of
antibacterial effect of seven 1-monoglycerides on food-
borne pathogens or spoilage bacteria. Acta Vet., 80:
29-39. DOI: 10.2754/avb201180010029
Lupiani, B. and S.M. Reddy, 2009. The history of
avian influenza. Comp. Immunol. Microbiol. Inf.
Dis., 32: 311-23. DOI: 10.1016/j.cimid.2008.01.004
Mansour, N., A.E. Yousef and J.G. Kim, 1996. Inhibition of
surface growth of toxigenic and nontoxigenic aspergilli
and penicillia by eugenol, isoeugenol and
monolaurin. J. Food Safety, 16: 219-229.
DOI: 10.1111/j.1745-4565.1996.tb00162.x
Bunkova, L., J. Krejci R. Janis V. Kasparkova and
P.
Vltavska et al., 2010. Influence of monoacylglycerols
on growth inhibition of micromycetes in vitro and
on bread. Eur. J. Lipid Sci Tech., 112: 173-179.
DOI: 10.1002/ejlt.200900070
130

Palaniappan Maheswari and Kasthuri Revathi / Journal of Biochemistry and Biotechnology 2017, 13 (3): 123.131
DOI: 10.3844/ajabssp.2017.123.131
Marshall, G.R., 1987. Computer-aided drug design.
Ann. Rev. Pharmacol. Toxicol., 27: 193-213.
DOI: 10.1146/annurev.pa.27.040187.001205
McNicholl, I.R. and J.J. McNicholl, 2001. Neuraminidase
inhibitors: Zanamivir and oseltamivir. Ann.
Pharmacother., 35: 57-70. DOI: 10.1345/aph.10118
Morris, G.M., H. Ruth, W. Lindstrom, M.F. Sanner and
R.K. Belew et al., 2009. AutoDock4 and
AutoDockTools4: Automated docking with selective
receptor flexibility. J. Comput. Chem., 30: 2785-2791.
DOI: 10.1002/jcc.21256
Schlievert, P.M., J. Deringer, M.H. Kim S.J. Projan and
R.P. Novick, 1992. Effect of glycerol monolaurate on
bacterial growth and toxin production. Antimicrob
Agents Ch., 30: 626-631. DOI: 10.1128/AAC.36.3.626
Serrano, M.C., M. Ramirez, D. Morilla, A. Valverde and
M. Chávez et al., 2004. A comparative study of the
disc diffusion method with the broth microdilution
and Etest methods for voriconazole susceptibility
testing of Aspergillus spp. J. Antimicrob Chemother.,
53: 739-742. DOI: 10.1093/jac/dkh172
Skrivanova, E., M. Marounek, V. Benda and P. Brezina,
2006. Susceptibility of Escherichia coli, Salmonella sp.
and Clostridium perfringens to organic acids and
monolaurin. Vet. Med., 51: 81-88.
Nair, M.K.M., P. Vasudevan, T. Hoagland and K.
Venkitanarayanan, 2004. Inactivation of Escherichia
coli O157: H and listeria monocytogenes in milk by
7
caprylic acid and monocaprylin. Food Microbiol.,
21: 611-616. DOI: 10.1016/j.fm.2004.01.003
Sun, C.Q., C.J. O’Connor, S.J. Turner, G.D. Lewis and
R.A. Stanley et al., 1998. The effect of pH on the
inhibition of bacterial growth by physiological
concentrations of butyric acid: Implications for
neonates fed on suckled milk. Chemi-Biol. Interact.,
113: 117-131. DOI: 10.1016/S0009-2797(98)00025-8
Wang, L.L. and E.A. Johnson, 1997. Inhibition of
listeria monocytogenes by fatty acids and
monoglycerides. J. Food Prot., 60: 131-138.
Shen, X., X. Zhang and S. Liu, 2013. Novel hemagglutinin-
based influenza virus inhibitors. J. Thorac. Dis., 5:
S149-S159.
Newell, D.G., M. Koopmans, L. Verhoef , E. Duizer and
A. Aidara-Kane et al., 2010. Food- borne diseases –
the challenges of 20 years ago still persist while new
ones continue to emerge. Int. J. Food Microbiol.,
139: S3- S15. DOI: 10.1016/j.ijfoodmicro.2010
Oh, D.H. and D.L. Marshall, 1993. Antimicrobial activity
of ethanol, glycerol monolaurate or lactic acid against
Listeria monocytogenes. Int. J. Food Microbio.,
20: 239-246. DOI: 10.1016/0168-1605(93)90168-G
Petrikkos, G., A. Skiada O. Lortholary E. Roilides and
T.J. Walsh et al., 2012. Epidemiology and clinical
manifestations of mucormycosis. Clin. Infect. Dis.,
54: S23-S34. DOI: 10.1093/cid/cir866
WHO, 2012. World Health Organization: Use of
antiviral drugs in poultry, a threat to their
effectiveness for the treatment of human avian
influenza. World Health Organization.
Razavi-Rohani, S.M. and M.W. Griffiths, 1994. The
effect of mono and polyglycerol laurate on
spoilage and pathogenic bacteria associated with
foods.
J.
Food
Safety.,
14:
131-151.
DOI: 10.1111/j.1745-4565.1994.tb00590.
Allen, U.D., F.Y. Aoki and H.G. Stiver, 2006. The use of
antiviral drugs for influenza: Recommended guidelines
for practitioners. Can. J. Infect Dis. Med. Microbiol.,
17: 273-284.
Rihakova, Z., V. Filip and J. Smidrkal, 2001. Antifungal
effectiveness of glycerol esters with lauric acid and its
dependency on their purity. Adv. Food Sci., 23: 57-62.
Ruzicka, J., K. Velclova, R. Janis and J. Krejci, 2003.
Antimicrobial effects of 1-monoacylglycerols prepared
by catalytic reaction of glycidol with fatty acids. Eur. J.
Lipid Sci. Tech., 2003; 217: 329-331.
Maheswari, P. and K. Revathi, 2016. Homology modeling
of S-adenosylmethionine synthase present in E.
maximum as a drug target and its docking with 1-
monocaproin. JCPR, 8: 1118-24.
131