Document Text (Pages 121-130) Back to Document

In Silico Drug Design of Biofilm Inhibitors of Staphylococcus epidermidis

by Al-mulla, Aymen Faraoun, MS


Page 121
3.15
1 x
8
10
400
Hypothetical Binding
energy to sarA = -5.4
Kcal/mol
3.75
1 x
8
10
600
0.07
3.89
4 x
7
10
0
+
7
FeNO
9
H
6
Formula C
M.W= 262.983
g/mol
Solubility:very
soluble
In water
Log p= -1.32
Hypothetical Binding
energy to sarA = -4.6
Kcal/mol
Ferric
ammonium
citrate
6
3.39
2.5 x
7
10
4
3.09
2.3 x
7
10
12
3.89
6.5 x
6
10
50
3.09
6.5 x
5
10
200
0.2
3.7
2.6 x
7
10
0
2
O
18
H
13
Formula C
M.W= 206.29 g/mol
Solubility: < 1 mg/ml
In water
Log p= 3.5
Hypothetical Binding
energy to sarA = -
11.99 Kcal/mol
Ibuprofen
7
3.6
x
2.5
7
10
1
3.0
2.6 x
7
10
10
3.0
2.8 x
7
10
50
3.1
1 x
7
10
200
2.4
1.4 x
7
10
600
2.15
0.8 x
6
10
900
1.95
0.2 x
6
10
1200

Page 122

1500

1800

0.6 x

5

10
0.5 x

5

10
1.75

1.35

A- Acetaminophen:
Paracetamol or acetaminophen chemically named N-acetyl-paminophenol,
is a widely used analgesic , antipyretic and antiinflammatory
drug. It belongs to the (NSAIDs) family. It was selected as
antibiofilm because its hypothetical binding energy to sarA protein was (-
5.37 kcal/mol). The antibiofilm activity of acetaminophen is shown in
(Figures 4.34 A,B), where it is shown that at the concentration 11 mg/ml
biofilm OD value fell to 0.05, while bacterial growth was not affected. The
correlation coefficients for VC and slime OD with concentration were -
0.65, -0.96 respectively. The effect of the drug on VC is statistically not
significant as the log dose not exceed one logarithmic cycle (Jarvis et al.,
1977).


Page 123

A

B

Figure 4.34 Effect of gradient concentrations of Acetaminophen on: A- bacterial
growth; B- slime production


Page 124

Log
cfu/ml

B- Acetylsalicylic Acid:
Aspirin, also known as acetylsalicylic acid, is a salicylate drug, often
used as an analgesic, antipyretic and anti-inflammatory medication. It also
belongs to the “NSAID” family. Aspirin also has an antiplatelet effect by
inhibiting the production of thromboxane. It was selected as an antibiofilm
because its hypothetical binding energy to sarA protein was (-0.05
kcal/mol). From (Figures 4.35 A,B) aspirin appears to inhibit biofilm at 1.6
mg/ml concentration with no significant change in bacterial growth. The
correlation coefficient for slime OD with concentration was -0.92.

8
7
6
5
4
3
2
1
0

0 500 1000 1500 2000 2500
Concentration (µg/ml)

A


Page 125

B

Figure 4.35 Effect of gradient concentrations of Acetylsalicylic Acid on: A-bacterial
growth; B-slime production

C- Acetic Acid:
Acetic acid is an organic, colourless liquid that, when concentrated, is
called glacial acetic acid. This acid is the main component of vinegar. It
has a distinctive sour taste and pungent smell. Although it is classified as
a weak acid, concentrated acetic acid is corrosive and harms the skin. It
was selected as an antibiofilm because its hypothetical binding energy to
the sarA protein was (-23.01 kcal/mol). From (Figures 4.36 A, B) it seems
that the acetic acid has moderate antibiofilm activity because at 1 mg/ml
concentration bacterial growth did not change but biofilm activity
decreased by 25%. The correlation coefficients for VC and slime OD with
concentration were -0.97, -0.76 respectively.


Page 126

Log
cfu/ml
8
7
6
5
4
3
2
1
0

0 500 1000 1500 2000 2500 3000 3500
Concentration (µg/ml)

A

B

Figure 4.36 Effect of gradient concentrations of Acetic Acid on: A-bacterial growth;
B-slime production


Page 127

Log
cfu/ml

D- Diacetyl:
Diacetyl is an organic volatile, yellow liquid with an intensely buttery
flavor. It is a vicinal diketone (two C=O groups, side-by-side). It occurs
naturally in alcoholic beverages and is added to some foods to impart a
buttery flavor. It was selected as an antibiofilm because its hypothetical
binding energy to the sarA protein was (-12.63 kcal/mol). Figures (4.37
A,B) demonstrate that diacetyl is a poor antibiofilm where bacterial growth
decreased as concentration increased which means it is a good antibacterial
but a poor antibiofilm. The correlation coefficients for VC and slime OD
with concentration were -0.99, -0.8 respectively.

8
7
6
5
4
3
2
1
0

0 200 400 600 800 1000 1200 1400 1600 1800
Concentration (µg/ml)

A


Page 128

B

Figure 4.37 Effect of gradient concentrations of Diacetyl on: A-bacterial growth; B-
slime productin

E- Ferric Ammonium Citrate:
The FAC, also named Ammonium ferric citrate, is a food
additive with E number E381 used as an acidity regulator. It is a green or
reddish-brown powder which is very soluble in water. Other uses for
ammonium ferric citrate include water purification. In medicine, it is used
as a hematinic. It was selected as an antibiofilm due to its hypothetical
binding energy to the sarA protein (-4.6 kcal/mol). The relation between
bacterial growth, slime production and Ferric Ammonium Citrate is shown
in (Figure 4.38 A,B) where it is found to have good antibacterial but not
antibiofilm activity. The correlation coefficients for VC and slime OD with
concentration were -0.98, -0.44 respectively.


Page 129

Log
cfu/ml
8
7
6
5
4
3
2
1
0

0 50 100 150 200 250
Concentration (µg/ml)

A

B

Figure 4.38 Effect of gradient concentrations of Ferric Ammonium Citrate on: A-
bacterial growth; B-slime productin


Page 130

Log
cfu/ml

F- Ibuprofen:
Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) used as
antipyretic, analgesic and anti-inflammatory. Ibuprofen has
an antiplatelet effect, though relatively mild and somewhat short-lived
compared with aspirin or other antiplatelet drugs. It was selected as an
antibiofilm because its hypothetical binding energy to the sarA protein (-
11.99 kcal/mol). Figures (4.39 A,B) demonstrate that the drug at 600 μg/ml
concentration decreases biofilm activity by 35% without change in
bacterial growth, while above this concentration the bacterial count begins
to decrease. The correlation coefficients for VC and slime OD with
concentration were -0.98 for both.

8
7
6
5
4
3
2
1
0

0 500 1000 1500 2000
Concentration (µg/ml)

A

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