International Journal of Advanced Research in Engineering and Technology

(IJARET)
Volume 6, Issue 10, Oct 2015, pp. 42-50, Article ID: IJARET_06_10_009
Available online at
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ISSN Print: 0976-6480 and ISSN Online: 0976-6499
IAEME Publication
___________________________________________________________________________

ANTIBACTERIAL ACTIVITIES OF
FRIEDEL-CRAFTS REACTION ON BAYLISHILLMAN ADDUCTS DERIVED FROM
NITROOLEFINS
Bosco Dhanaseeli. P
Department of chemistry, AMET University
ABSTRACT
The purpose of this study was to determine the antibacterial activity of
nitro olefins. The nitro olefins were tested on MRSA and MSSA from hospital
patients using the disk diffusion (Kirby Bauer) method. Based on this study, all
nitro olefins showed higher effectiveness inhibiting MRSA and MSSA growth
than vancomycin, which is the currently used standard for treatment. Nitro
olefins could be especially beneficial towards treating hospital patients with
MRSA or MSSA infections in areas where antibiotics are not readily available.
Key words: Methicillin sesitivity Staphylococcus aureus (MRSA), Methicillin
Sensitive Staphylococcus aureus (MSSA), Essential oils, Antibacterial. BaylisHillman adducts.
Cite this Article: Bosco Dhanaseeli. P. Antibacterial Activities of FriedelCrafts Reaction on Baylis-Hillman Adducts Derived From Nitroolefins.
International Journal of Advanced Research in Engineering and Technology,
6(10), 2015, pp. 42-50.
http://www.iaeme.com/IJARET/issues.asp?JType=IJARET&VType=6&IType=10

1. INTRODUCTION
In order to fight bacterial infections, medicine has largely relied on antibiotics, which
are naturally occurring or artificially created chemical substances capable of killing or
controlling the growth of bacteria. In present times, however, bacteria have developed
sensitive to many of the antibiotics commonly used to treat infections [1]. Amine
compound Staphylococcus aureus (MSSA) is an example of a superbug or bacterial
strain of Staphylococcus aureus that has developed sensitive to Amine, an antibiotic
which is part of a class known as the nitro olifen. Nitro Olifen antibiotics are capable
of killing a variety of Gram positive and Gram negative microorganisms by impairing
the cells ability to form benzene, a necessary component for cell structure and
stability. Bacteria that have become sensitive developed enzymes known as

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Antibacterial Activities of Friedel-Crafts Reaction on Baylis-Hillman Adducts Derived From

Nitroolefins

penicillinases and beta-lactamases, which are capable of destroying the benzene ring
structure or functional group of these antibiotics. Amine Sensitive Staphylococcus
aureus (MSSA) causes a type of staph infection that is moderately sensitive to these
antibiotics [2].
Staphylococcus aureus is an opportunistic pathogen that mainly colonizes the
nares and skin of up to 80% of the population [3]. S. aureus is a Gram-positive cocci
that is frequently isolated in hospitals, and is responsible for diverse infections and
toxicoses [4]. S. aureus is the most common cause of skin and soft-tissue infections
(such as impetigo, furunculosis, and abscess), as well as systemic infections (such as
pneumonia and endocarditis) [5]. The threat of S. aureus is not only due to its
distribution and pathogenicity [6], but also because of its ability to overcome
antimicrobial agents [7]. Virulence factors produced by S. aureus render this organism
highly pathogenic. The known virulence factors include exotoxins, such as exfoliative
toxins (ETs), along with toxic shock syndrome toxin-1 (TSST-1), staphylococcal
enterotoxins (SEs), leukocidins (Panton-Valentine leukocidin; PVL, LukE/D), and
hemolysins (, , , ). Enterotoxins often cause food poisoning [8], while ETs (also
called epidermolysins) act on the skin [9]. Among the leukocidins, PVL is an
extracellular protein consisting of two subunits, F and S, which act in concert and
have leucocidal and dermonecrotic functions. The PVL toxin targets the outer
membrane of polymorphonu clear cells, monocytes, and macrophages [10]. S. aureus
strains that are positive for PVL are usually associated with skin and soft-tissue
infections, and were first isolated in the 1960s [11]. PVL-positive strains are
particularly associated with furuncles, accounting for 96% of cases [12,13,14], and
approximately 90% of PVL-positive S. aureus strains were originally isolated from
furuncles. PVL has also been associated with severe infections, including necrotizing
pneumonia [15], osteomyelitis, and even cases of purpura fulminans [16]. PVL toxin
was recently identified in Lemierres syndrome, and in a case of Fourniers gangrene
PVL has also been associated with community-acquired necrotizing and hemorrhagic
pulmonary infections affecting previously healthy children and young adults [17].
Several antibiotics were routinely used in the treatment of S. aureus infections,
contributing to the emergence of antibiotic-sensitive strains. Widespread sensitive
severely complicates management of S. aureus infections. S. aureus strains that are
sensitive to Amine derived compounds (amine-sensitive S. aureus, ASSA) are
pervasive in the hospital environment, and have recently also caused a global
epidemic of community-associated S. aureus (CA-ASSA) infections [18]. The
objective of this work was to study the Sensitivity profile and toxin production of S.
aureus strains isolated from various skin, soft tissue, and bone infections.

2. SENSITIVITY TO ANTIBIOTICS
There was a wide range in the sensitivity of the isolates to the various antibiotics
examined. All of the strains were sensitive to nitro olifen derivatives, while other
antibiotics (vancomycin, fusidic acid, fosfomycin, and linezolid) were active against
some of the strains. There was no significant difference in the antibiotic resistance of
the strains based on their origin S. aureus strains originating from pyomyositis,
furuncles and osteomyelitis cases (were resistant to 4/17 tested antibiotics (benzyl
penicillin, rifampincin, tetracycline, and trimetroprim/sulfamethoxazol), while strains
originating from abscesses and Buruli ulcer were strongly resistant to respectively
13/17 and 7/ 17 of the tested antibiotics. Of the 136 isolated S. aureus strains, 34
(25%) were resistant to oxacillin (MRSA), while none of the strains showed

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Bosco Dhanaseeli. P

resistance to vancomycin (VRSA). The oxacillin-resistant strains were all isolated

from abscesses and Buruli ulcers.
This bioactive study which shows enhanced activity under acidic pH, and that of
N-(2-nitro-1, 3-diphenylpropyl) aniline derivatives sensitive against 1. Bacillus
subtilis; 2. Escherichia coli; 3. Staphylococcus aureus; 4. Pseudomonas aeruginosa;
5. Klebsella pneumonia under standard conditions (pH 8.2) and at a pH of 5.8. Hence,
N-(2-nitro-1, 3-diphenylpropyl)aniline could be a promising new antimicrobial
agent for the treatment of. Bacillus subtilis; 2. Escherichia coli; 3. Staphylococcus
aureus; 4. Pseudomonas aeruginosa; 5. Klebsella pneumonia infections at acidic
body compartments.

3. MECHANISM OF ACTION
N-(2-nitro-1, 3-diphenylpropyl) aniline

4. RESULT AND DISCUSSION

The newly synthesized compounds benzoxepine derivatives dissolved in 40% DMSO
were evaluated for in-vitro antimicrobial activity studies against microorganisms and
results are discussed. The bioactivity studies were carried out against bacteria,
Staphylococcus aureus, Bacillus Subtilis, Pseudomonos aeruginosa, Klebsiella
pneumonia and Escherichia coli.

4.1. Antibacterial activity of benzoxepine derivatives (agar diffusion assay)

The agar diffusion method was used for the determination of antibacterial activity of
novel benzoxepine derivatives (2a-2k) against microorganism listed above. About 15
ml of nutrient agar media were poured into Petri plates (9 cm in diameter) and
inoculated with respective test organism. Wells are made with corn borer on the solid
agar and loaded with 50, 75, 100 g/well of the test compound with tetracycline as
positive control and control served as 40% DMSO. Petri dishes were incubated at 37
C for 24 h and the average diameter of the inhibition zone surrounding the wells were
measured after specified incubation period.
The percentage of inhibition zone was calculated by using following formula.
Zone of inhibition (diameter in mm)
% of Inhibition zone =
Diameter of the Petri plate in mm

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Antibacterial Activities of Friedel-Crafts Reaction on Baylis-Hillman Adducts Derived From

Nitroolefins

The antibacterial activity of the benzoxepines 2a-2j were evaluated against five
human pathogens namely Bacillus subtilis, Klebsiella pneumonia, Staphylococcus
aureus, Pseudomonas aeruginosa, and Escherichia coli by the agar diffusion method.
All the compounds were tested, each at 50 g, 75 g and 150 g/well concentration to
test their efficacy in inhibiting the growth of the tested pathogens (human
pathogenic).
The benzoxepines derivatives are efficiently inhibited the growth of Bacillus
subtilis, Klebsiella pneumoniae, Pseudomonas aeruginos, Staphylococcus aureus and
Escherichia coli (Table 1and 2). The benzoxepine derivatives system showed good
antimicrobial activity against respective test bacteria using 100 g/well
concentrations. In addition of the compounds 1b, 2d, 2f, 2h and 2i were effectively
inhibited the growth of the five human pathogenic bacteria. The compound 2d
showed good activity against gram (-) and gram (+) bacteria than the other
compounds (Table 1). Compound 2b, 2f and 2h were showed significant activity than
the compound 2c and 2d against Bacillus subtilis. Among the derivatives 2e was not
showed any remarkable activity. All the compounds 2a-i showed effective
antimicrobial activity against Pseudomonas aeruginos and Staphylococcus aureus
than the other human pathogenic bacteria. The 2f compounds showed good activity
against all bacterial pathogens while compared to rest compounds (Figure 1.a).
Table 1 The minimum inhibitory concentration (MIC) g/ml of benzoxepine derivatives
against human pathogens
Compound test using well diffusion methods
Human
pathogens

2a

2b

2c

2d

2e

2f

2g

2h

2i

2j

+++

+++

++

++

+++

+++

+++

+++

+++

+++

+++

+++

+++

++

+++

+++

+++

+++

+++

+++

+++

++

++

+++

++

++

+++

Pseudomonas
argenosa

+++

+++

+++

++

++

+++

+++

+++

+++

+++

Klebciella
pneumonia

+++

+++

++

++

+++

+++

+++

Bacillus subtilis

Staphylococcs
areus
Escherichia coli

Note:
+++ = Excellent
++ = Moderate
- = No activity

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Bosco Dhanaseeli. P
Table 2 Antibacterial activity of benzoxepines derivatives against human pathogens
Benzoxepines
(g/well)
50
75
100
Positive control
50
206b
75
100
Positive control
50
206c
75
100
PC
50
206d
75
100
Positive control
50
206e
75
100
Positive control
50
2f
75
100
Positive control
50
2g
75
100
Positive control
50
2h
75
100
Positive control
50
2i
75
100
Positive control
50
2j
75
100
Positive control
206a

Bacillus
subtilis
(mm)

Escherichia
coli
(mm)

Staphylococcus
aureus
(mm)

Pseudomonas
argenosa
(mm)

Klebciella
pneumonia
(mm)

12
16
20
24
14
14
16
24
6
8
12
24
6
8
10
24
NA
NA
NA
24
16
17
18
24
10
11
13
24
13
15
17
24
12
16
17
24
NA
10
13
24

20
22
24
26
10
12
20
26
NA
NA
NA
26
8
10
12
26
10
11
12
26
14
17
20
26
10
11
12
26
NA
10
12
26
11
12
16
26
NA
NA
NA
26

12
16
20
24
16
18
20
24
14
16
20
24
10
18
18
22
8
10
12

16
20
24
26
12
20
26
26
10
12
14
26
6
8
10
26
6
8
12

16
18
20
24
17
18
19
24
13
14
17
24
13
13
15
24
13
14
15
24

14
15
18
26
15
16
16
26
13
15
17
26
10
12
15
26
11
13
14
26

NA
NA
NA
21
8
12
14
21
6
10
12
21
4
4
6
21
NA
NA
NA
21
13
15
17
21
NA
NA
NA
21
13
14
15
21
14
16
17
21
NA
NA
NA
21

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Antibacterial Activities of Friedel-Crafts Reaction on Baylis-Hillman Adducts Derived From

Nitroolefins

NA = No activity
Positive control = tetracycline

1. Bacillus subtilis; 2.

Escherichia coli; 3. Staphylococcus aureus; 4. Pseudomonas

aeruginosa; 5. Klebsella pneumonia
a-control; b-positive control; c-50g/ml; d-75g/ml; e-100g/ml
Figure 1.a. Bioactive studies of benzoxepine derivatives

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Bosco Dhanaseeli. P

1. Bacillus subtilis; 2. Escherichia coli; 3. Staphylococcus aureus; 4. Pseudomonas

aeruginosa; 5. Klebsella pneumonia
a-control; b-positive control; c-50g/ml; d-75g/ml; e-100g/ml
Figure 1.b. Bioactive studies of benzoxepine derivatives

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Antibacterial Activities of Friedel-Crafts Reaction on Baylis-Hillman Adducts Derived From

Nitroolefins

1. Bacillus subtilis; 2. Escherichia coli; 3. Staphylococcus aureus; 4. Pseudomonas

aeruginosa; 5. Klebsella pneumonia
a-control; b-positive control; c-50g/ml; d-75g/ml; e-100g/ml
Figure 1.c. Bioactive studies of benzoxepine derivatives

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Bosco Dhanaseeli. P

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