ª 2010 John Wiley & Sons A/S

Chem Biol Drug Des 2010; 76: 407–411 doi: 10.1111/j.1747-0285.2010.01020.x

Research Article

Novel chalcones and 1,3,5-triphenyl-2-pyrazoline

derivatives as antibacterial agents

Ponnurengam Malliappan Sivakumar*, Received 21 June 2010, revised 21 June 2010 and accepted for publica-
Suresh Ganesan, Prabhawathi Veluchamy tion 3 July 2010
and Mukesh Doble*
Bacterial infection and their emergence to resistance toward anti-
Department of Biotechnology, Indian Institute of Technology biotics is a serious threat to present and future populations. These
Madras, Adyar, Chennai 600 036, India resistant bacteria are involved in diseases including diarrhea,
*Corresponding author: Mukesh Doble, mukeshd@[Link] respiratory tract infections, meningitis, sexually transmitted infec-
tions, and hospital-acquired infections (nosocomial infections).a The
The authors Ponnurengam Malliappan Sivakumar, Suresh Ganesan and use of more antibiotics or less antibiotics leads to the develop-
Prabhawathi Veluchamy wishes to dedicate this work to their guide Prof ment of drug resistance in bacterial strains. These resistant strains
MD on the occassion of his birthday
cause fatal morbidity and also death in patients who are already
infected with the disease and hence are immunocompromised (1).
Novel sixteen chalcones and thirteen 1,3,5-triphe- Clinical isolates of Escherichia coli O157 from human, cattle,
nyl-2-pyrazolines were synthesized and character- swine, and food sources were found to be resistant against the
ized using FT-IR, HR-Mass, NMR (1H-NMR, 13C-NMR, frontline antibiotics, tetracycline, sulfa drugs, cephalosporins, and
135 DEPT, 1H–1H CoSY and 1H and 13C CoSY) and penicillins (2). b-lactamases produced by E. coli has developed
XRD. These compounds were evaluated for their resistance to b-lactam antibiotics (3). It is found that the muta-
antibacterial activity against six micro-organisms, tions that affect the expression of chromosomal class I, b-lactam-
namely Bacillus subtilis NCIM 2718, Staphylococ-
ase expression in Pseudomonas aeruginosa and Proteus vulgaris
cus aureus NCIM 5021, Salmonella typhi NCIM
can lead to resistance against many newer b-lactam antibiotics
2501, Enterobacter aerogenes NCIM 5139, Pseudo-
monas aeruginosa NCIM 5029, and Proteus vulgaris (4). Seventy to eighty percentage of Staphylococcus aureus strains
NCIM 2813 by twofold dilution method using res- are resistant against penicillins, whereas methicillin was effective
azurin as the indicator dye. In the case of chal- until 1980. Methicillin-resistant S. aureus produces a penicillin-
cones, compounds with hydroxyl and bromo binding protein PBP2a, which binds less with methicillin and other
substitutions in the B-ring favor activity and benzyl- b-lactams that are present in the bacterial cell wall (3). Vancomy-
oxy substitution irrespective of its position in the cin was effective against methicillin-resistant S. aureus, but resis-
A-ring. In the case of 1,3,5-triphenyl-2-pyrazolines, tance against glycopeptide class of vancomycin had delineated the
chloro substitution in the A-ring favors activity. therapy (5). Salmonella typhi responds to ciprofloxacin by inducing
Hydrophilic ⁄ lipophilic balance of the compounds
double mutation in gyrA and single mutation in parC genes (6).
plays a major role in their antibacterial activity.
Streptomycin-resistant Bacillus subtilis has two mutations namely
Key words: 1,3,5-triphenyl-2-pyrazolines, antibacterial, resazurin fun and strR (7).

Antibacterial evaluation by two fold dilution method using resazurin dye

MIC

Chalcones

Color change denotes bacterial growth

1,3,5-Triphenyl-2-
pyrazolines

407
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Sivakumar et al.

Although methicillin, vancomycin and linezolid are designed to com- acetophenone derivatives were added together with methanol
bat the problem of antibiotic resistance, the micro-organisms have (10 mL) and stirred at room temperature. Two molar NaOH solutions
developed resistance to these drugs as well. So there is a need for was added to the above mixture and maintained under rapid stir-
newer drugs to treat the bacterial infections and combat the bacte- ring at room temperature. In majority of the cases, an almost pale
rial resistance. Hence, medicinal chemists have to discover new yellowish solid precipitate was obtained, which was washed with
chemical moieties that may exhibit anti-infective properties. Chal- 50% ethanol followed by water, recrystallized and then dried. The
cones are such small molecules that have been known to exhibit a yield in most of the cases was more than 80%.
wide range of activities including antibacterial, antifungal, antituber-
cular, and antioxidant. Pyrazolines are another class of small mole-
cules that can be prepared using chalcones as the starting Synthesis of 1,3,5-triphenyl-2-pyrazolines
material. Appropriate chalcone (4 mmol) was mixed with 8 mmol of phen-
ylhydrazine and 10 mL of acetic acid (17). It was boiled under reflux
Alcaraz et al. (8) tested eleven natural and synthesized chalcones for 2–7 h. The synthesized 1,3,5-triphenyl-2-pyrazoline usually pre-
for antistaphylococcal activity against methicillin-resistant S. aureus cipitated out on cooling, but in some cases, it was precipitated out
and showed the importance of the carbonylic region for its perfor- by adding 50% of aqueous ethanol. In majority of the cases, the
mance. Asebogenin, which was isolated from licorice, was active yield was more than 70%.
against methicillin-resistant S. aureus (MRSA) with an IC50 of
4.5 lg ⁄ mL (9). Earlier, our research has proved that chalcones are
very active against Gram-positive and Gram-negative bacteria (10), Antibacterial activity evaluation
fungi (11), and resistant antimycobacterial strain, Mycobacterium In vitro antibacterial inhibitory activities (MIC) of the chalcones
tuberculosis H37Rv (12). and 1,3,5-triphenyl-2-pyrazolines were determined by microdilution
broth assay method (18) using resazurin as an indicator (19).
1-Aryloxy-3-aryl-5-hydroxy-5-aryl-pyrazolines (13), sulfone-linked bis Muller-Hinton broth was used to culture the bacterial strains to a
heterocycle pyrazolines in combination with thiadiazoles, oxadiaz- final inoculum size of 5 · 105 CFU ⁄ mL. The chalcones and 1,3,5-tri-
oles, and triazoles (14), N1-substituted 3,5-diphenyl pyrazolines phenyl-2-pyrazolines were dissolved in absolute ethanol to a
(15) have been evaluated as antibacterial agents by other concentration of 10 mg ⁄ mL (20). Serially diluted chalcone and 1,3,5-
researchers. triphenyl-2-pyrazoline solutions were added to successive wells in a
96-well microtitre plate and incubated with respective micro-organ-
Hydrophobic substitutions in the A-ring of chalcone are considered ism for 18 h at 37 C. After the incubation period, 10 lL of 0.01%
to be more active (16). Hence, we attempted to synthesize resazurin solution was added and incubated for 2 h. The color
chalcones A-ring with benzyloxy and chloro substitutions at R1 and change was assessed visually. Growth of organism changed the
R2 positions (in the A-ring) and their corresponding 1,3,5-triphenyl- color from blue to pink. Growth and sterility controls were also
2-pyrazolines (substitutions at R1) to test their antibacterial activity. maintained during the experiment. Test compounds serially diluted
These compounds are novel and their synthesis has not been with ethanol were also kept in the 96-well microtitre plates (unin-
reported elsewhere. oculated dilution) to determine whether they precipitated out during
the course of the experiments. One entire column had antibiotics as
a positive control (norfloxacin ⁄ erythromycin). A blank assay with
Materials and Methods
ethanol alone was taken into account to discount any possible
effect of the solvent.
All the chemicals used for the synthesis and antibacterial evalua-
tions were purchased from Sigma-Aldrich (St. Louis, MO, USA),
Hi-media (Mumbai, India) and SRL (Mumbai, India) and the bacte- Results and Discussions
rial strains (B. subtilis NCIM 2718, S. aureus NCIM 5021, S. typhi
NCIM 2501, Enterobacter aerogenes NCIM 5139, P. aeruginosa The chalcones and 1,3,5-triphenyl-2-pyrazolines were synthesized
NCIM 5029, and Proteus vulgaris NCIM 2813) were purchased (Tables 1 and 2) and characterized by NMR (1H, 13C, DEPT, 1H–1H
from National Chemical Laboratory, Pune, India. The following CoSY, 1H–13C CoSY), mass (HR-MS) spectroscopy. Reference (21)
scheme shows the synthesis of chalcones and 1,3,5-triphenyl-2- gives the NMR, HR-MS data for a representative chalcone and
pyrazolines: 1,3,5-triphenyl-2-pyrazoline. The synthesized compounds were tested
for antibacterial activity against six bacterial strains including Gram-
Synthesis of chalcones positive and Gram-negative, namely S. aureus NCIM 5021, B. subtil-
The various substituted chalcones were synthesized based on the is NCIM 2718, P. vulgaris NCIM 2813, E. coli NCIM 2931, S. typhi
method described by Lin et al. (17). Ten millimoles of the corre- NCIM 2501, and P. aeruginosa NCIM 5029 by twofold dilution assay
sponding substituted benzaldehydes and 1 mmol of the using reaszurin as an indicator. Tables 1 and 2 lists the antibacterial

O
CHO COCH3 N N R1
C6H5NHNH2
EtOH
R1 CH3COOH
R1 NaOH
R R
R

408 Chem Biol Drug Des 2010; 76: 407–411

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Antibacterial chalcones and pyrazolines

Table 1: Structure and antibacterial activities (in lM) of chalcones

R1 O R3
R4
A B
R2 R5

Antibacterial activity
(against Gram-positive Antibacterial activity (against Gram-negative
Substitutions at A-ring Substitutions at B-ring organisms) organisms)

Bacillus Staphylococcus Pseudomonas Escherichia Salmonella Proteus

Compound No R1 R2 R3 R4 R5 subtilis aureus aeruginosa coli typhi vulgaris

PMS-1 C6H5CH2O OCH2CH3 0.349 0.697 0.349 0.174 0.174 0.174

PMS-2 C6H5CH2O F 0.376 0.376 0.376 0.188 0.188 0.188
PMS-3 C6H5CH2O Br 0.636 0.636 0.318 0.020 0.159 0.159
PMS-4 C6H5CH2O OH 0.378 0.378 0.378 0.012 0.189 0.095
PMS-5 C6H5CH2O OH 0.378 0.378 0.189 0.024 0.189 0.095
PMS-6 C6H5CH2O Cl 0.358 0.717 0.358 0.179 0.179 0.179
PMS-7 Cl OCH2CH3 0.436 0.872 0.436 0.218 0.218 0.218
PMS-8 Cl OCH3 OCH3 0.413 0.826 0.413 0.206 0.206 0.103
PMS-9 Cl F 0.479 0.479 0.479 0.240 0.240 0.240
PMS-10 Cl Cl 0.451 0.902 0.451 0.226 0.113 0.226
PMS-11 Cl Br 0.777 0.777 0.389 0.194 0.194 0.194
PMS-12 Cl OCH2O 0.872 0.872 0.436 0.218 0.218 0.218
PMS-13 Cl OCH3 OCH3 0.826 0.826 0.413 0.206 0.206 0.206
PMS-14 Cl OCH3 0.458 0.917 0.458 0.229 0.115 0.229
PMS-15 Cl Cl 0.902 0.902 0.451 0.226 0.226 0.226
PMS-16 C6H5CH2O Br 0.636 0.318 0.318 0.159 0.318 0.159
PMS-17 C6H5CH2O F 0.376 0.376 0.376 0.188 0.376 0.188
Ampicillin 0.168 0.084 0.084 0.005 0.084 0.168
Tetracycline 0.001 0.002 0.002 0.001 0.004 0.001

Table 2: Structure and antibacterial activities (in lM) of 1,3,5-triphenyl-2-pyrazoline derivatives

R2 R3
N N
B R4

A
R1

Antibacterial activity
(against Gram-positive Antibacterial activity (against Gram-negative
Substitutions at A-ring Substitutions at B-ring organisms) organisms)

Bacillus Staphylococcus Pseudomonas Escherichia Salmonella Proteus

Compound No R1 R2 R3 R4 subtilis aureus aeruginosa coli typhi vulgaris

PMSPY-1 C6H5CH2O OCH2CH3 1.115 0.557 0.557 1.115 0.139 0.139

PMSPY-2 C6H5CH2O F 2.367 2.367 1.183 0.592 0.148 0.148
PMSPY-3 C6H5CH2O Br 1.034 1.034 0.517 1.034 0.259 0.129
PMSPY-4 C6H5CH2O OH 0.595 0.297 0.297 1.189 0.297 0.149
PMSPY-5 Cl OCH2CH3 0.663 0.332 0.332 2.653 0.332 0.166
PMSPY-6 Cl OCH3 OCH3 0.636 0.318 0.159 0.636 0.159 0.159
PMSPY-7 Cl F 0.713 0.356 0.356 0.713 0.178 0.178
PMSPY-8 Cl Cl 0.681 0.340 0.170 0.681 0.170 0.170
PMSPY-9 Cl Br 0.304 0.304 0.152 0.607 0.152 0.076
PMSPY-10 Cl –OCH2O– 0.663 0.332 0.332 0.663 0.166 0.166
PMSPY-11 Cl OCH3 OCH3 0.636 0.318 0.159 0.636 0.159 0.159
PMSPY-12 Cl OCH3 0.689 0.689 0.172 0.344 0.172 0.172
PMSPY-13 Cl Cl 0.681 0.681 0.170 0.681 0.170 0.170
Ampicillin 0.168 0.084 0.084 0.005 0.084 0.168
Tetracycline 0.001 0.002 0.002 0.001 0.004 0.001

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Sivakumar et al.

activity of chalcones and 1,3,5-triphenyl-2-pyrazolines, respectively, compounds PMS-9, PMS-10, PMS-14, and PMS-15 were
in terms of micromolar (lM) concentration. least active. The more active compounds have essential features
like hydroxyl substitution in B-ring, substitution at R4, and hydropho-
Chalcones PMS-1, PMS-3, PMS-4, PMS-5, and PMS-16 bic substitution like benzyloxy in the A-ring. Chloro substitution in
were more active (at least against four of the six strains) and A-ring leads to medium to lower active compounds. In the case of
compounds PMS-9, PMS-10, PMS-14, and PMS-15 were 1,3,5-triphenyl-2-pyrazolines, compounds PMSPY-6, PMSPY-9,
least active (at least against four of the six strains) in general PMSPY-10, and PMSPY-11 were the most active ones and
when compared to others against all six bacterial strains. compounds PMSPY-1, PMSPY-2, and PMSPY-3 were the
least active. All the most active 1,3,5-triphenyl-2-pyrazolines have
The most active compounds have benzyloxy substitution either in chloro substitution in their A-ring at R1 position. The least active
the R1 or in the R2 position in A-ring which is the hydrophobic ring compounds PMSPY-1, PMSPY-2, and PMSPY-3 have benzyl-
(10) in chalcone, and compounds PMS-3 and PMS-16 have bro- oxy substitution in their A-ring at R1 position. In conclusion,
mine in their R4 position of the B-ring. It is also observed that com- lipophilic ⁄ hydrophilic balance is required for antibacterial activities
pounds which have substitution at R4 when compared to R5 and R3 of chalcones and 1,3,5-triphenyl-2-pyrazolines. Our studies revealed
positions were more active, which was observed by other research- that, in the case of chalcone, A-ring requires slightly hydrophobic
ers too (16,22). It is found that the substitution in the B-ring is substitution including benzyloxy substitution and B-ring requires
important for antibacterial activity (22). Compounds PMS-4 and hydrophilic substitution including hydroxyl and bromo groups. It is
PMS-5 have hydroxyl substitution in their B-ring at R5 and R3 opposite in the case of 1,3,5-triphenyl-2-pyrazolines. Chloro substi-
position. Our earlier research and other researchers too have found tution is required in A-ring for the activity and slightly hydrophilic
the importance of hydroxyl and bromo substitutions in B-ring for substitution like dimethoxy and methylene dioxy compared to hydro-
enhanced antibacterial activity (10,16,23,24). Compound PMS-1 xyl substitution that is required for good antibacterial activity. A
has ethoxy substitution in R5 position of the B-ring. Alkoxy substitu- detailed group-based QSAR (GQSAR) could give more information
tion in R5 position of the B-ring was also found to be important for on structure–activity relationship, which will be performed and
the antibacterial activity (16). The least active compounds have published later. This research gives additional knowledge to
chloro substitution in their A-ring. The chloro-substituted chalcones researchers to design newer chalcones and 1,3,5-triphenyl-2-pyrazo-
(in A-ring) also exhibit activity when they have polar substitutions lines exhibiting antibacterial activity.
such as hydroxyl in their R4 position of the B-ring (25). Compounds
PMS-9, PMS-10, and PMS-15 have halogen substitution in
their B-ring. Lipophilic ⁄ hydrophilic balance appears to determine the References
antibacterial activity of chalcones. Even though increase in the
hydrophobic surface increases the antibacterial activity, it appears 1. Prevention of Hospital-Acquired Infections. A Practical Guide,
that the dipole and quadropole moments related to polarizability of 2nd edn, WHO ⁄ CDS ⁄ CSR ⁄ EPH ⁄ 2002.12; p. 55–57.
the molecules are also important (26). 2. Schroeder C.M., Zhao C., DebRoy C., Torcolini J., Zhao S., White
D.G., Wagner D.D., McDermott P.F., Walker R.D., Meng J. (2002)
In the case of 1,3,5-triphenyl-2-pyrazolines, compounds PMSPY-6, Antimicrobial Resistance of Escherichia coli O157 Isolated from
PMSPY-9, PMSPY-10, and PMSPY-11 were more active Humans, Cattle, Swine, and Food. Appl Environ Microbiol;
against at least four micro-organisms. The most active compounds 68:576–581.
have chloro substitution in R1 position at A-ring. Other researches 3. Coates A.R.M., Hu Y. (2008) Targeting non-multiplying organisms
also found that chloro substitution at R1 position in quinoline-based as a way to develop novel antimicrobials. Trends Pharmacol
2-pyrazolines exhibits very good activity when compared to chloram- Sci;29:143–150.
phenicol against S. aureus, S. typhi, and E. coli (27). Among the 4. Yang Y., Livermore D.M. (1988) Chromosomal 1-Lactamase
most active compounds, PMSPY-6 and PMSPY-11 have Expression and Resistance to b-Lactam Antibiotics in Proteus
dimethoxy substitution in B-ring. Compound PMSPY-9 has vulgaris and Morganella morganii. Antimicrob Agents Chemo-
bromine substitution at R3 position in the B-ring. Even though com- ther;32:1385–1391.
pound PMSPY-3 has bromine substitution in B-ring, it is inactive 5. Smith T.L., Pearson M.L., Wilcox K.R., Dr P.H., Cruz C., Lancaster
and the reason remains unclear. Compounds PMSPY-1, M.V., Robinson-Dunn B., Tenover F.C., Zervos M.J., Band J.D.,
PMSPY-2, and PMSPY-3 can be classified as least active, and White E., Jarvis W.R. (1999) Emergence of vancomycin
interestingly these compounds have benzyloxy substitution in the resistance in Staphylococcus aureus. N Eng J Med;340:493–
A-ring. 501.
6. Gaind R., Paglietti B., Murgia M., Dawar R., Uzzau S., Cappucci-
nelli P., Deb M., Aggarwal P., Rubino S. (2006) Molecular charac-
Conclusion terization of ciprofloxacin-resistant Salmonella enterica serovar
Typhi and Paratyphi A causing enteric fever in India. J Antimic-
In conclusion, the chalcones and 1,3,5-triphenyl-2-pyrazolines were rob Chemother;58:1139–1144.
synthesized and characterized. The synthesized compounds were 7. Henkin T.M., Chambliss G.H. (1984) Genetic analysis of a
also tested for antibacterial activity against six bacterial strains. In streptomycin-resistant oligosporogenous Bacillus subtilis mutant.
the case of chalcones, compounds PMS-1, PMS-3, PMS-4, J Bacteriol;157:202–210.
PMS-5, and PMS-16 were found to be more active and

410 Chem Biol Drug Des 2010; 76: 407–411

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Antibacterial chalcones and pyrazolines

8. Alcaraz L.E., Blanco S.E., Puig O.N., Tomas F., Ferretti F.H. (2000) PMS – 13: FTIR (KBr) 1665 cm)1(C=O). 1H NMR
Antibacterial activity of flavonoids against methicillin-resistant (500 MHz): d 3.97 (6H, s), 6.93 (1H, d, J = 8 Hz), d 7.37 (2H, dd,
Staphylococcus aureus strains. J Theor Biol;205:231–240. J = 8.5 Hz), d 7.56–7.58 (2H, m), d 7.61 (1H, d, J = 2 Hz), d
9. Joshi A.S., Li X.C., Nimrod A.C., ElSohly H.N., Walker L.A., Clark 7.67 (1H, dd, J = 2 Hz, J¢ = 8.5 Hz), d 7.75 (1H, d, J = 15.5 Hz).
13
A.M. (2001) Dihydrochalcones from Piper longicaudatum. Planta C NMR (500 MHz): d 56.05, 56.10, 109.98, 110.76, 122.08,
Med;67:186–188. 123.05, 129.16,129.19, 129.22, 129.50, 131.14, 133.57, 136.18,
10. Sivakumar P.M., Sobana P., Doble M. (2009) Synthesis, Biological 142.43, 149.31, 153.41, 188.23. HR-MS (m ⁄ z) for molecular for-
Evaluation, Mechanism of Action and Quantitative Structure– mula C17H15ClO3: calculated = 303.0784, found = 303.0788.
Activity Relationship Studies of Chalcones as Antibacterial. Spectral data for compound PMSPY – 7: FTIR (KBr)
Chem Biol Drug Des;73:403–415. 1587 cm)1(C=N). 1H NMR (500 MHz): d 3.06 (1H, dd,
11. Sivakumar P.M., Muthu Kumar T., Doble M. (2009) Antifungal J = 7.5 Hz, J¢ = 17 Hz), d 3.80 (1H, dd, J = 12.5 Hz, J¢ = 17 Hz),
Activity, Mechanism and QSAR Studies on Chalcones. Chem Biol d 5.23 (1H, dd, J = 7.5 Hz, J¢ = 12.5 Hz), d 6.78–6.81 (1H, m), d
Drug Des;74:68–79. 7.01–7.03 (2H, m), d 7.05–7.08 (2H, m), d 7.16–7.19 (2H, m), d
12. Sivakumar P.M., Seenivasan S.P., Kumar V., Doble M. (2007) Syn- 7.23–7.25 (2H, m), d 7.29–7.31 (2H, m), d 7.68–7.69 (2H, m). 13C
thesis, antimycobacterial activity evaluation, and QSAR studies NMR (500 MHz): d 43.55, 64.00, 113.38, 115.57, 115.75, 119.44,
of chalcone derivatives. Bioorg Med Chem Lett;17:1695–1700. 127.31, 127.51, 127.48, 127.54, 128.82, 128.84,128.99, 129.02,
13. Karthikeyan M.S., Holla B.A., Kumari N.A. (2007) Synthesis and 129.37, 133.39, 140.94, 144.63, 145.80, 162.08, 164.06. HR-MS
antimicrobial studies on novel chloro-fluorine containing hydroxy (m ⁄ z) for molecular formula C21H16ClFN2: calculated = 351.1064,
pyrazolines. Eur J Med Chem;42:30–36. found = 351.1064. Spectral data for compound PMSPY – 11:
14. Padmavathi V., Thriveni P., Sudhakar Reddy G., Deepti D. (2008) FTIR (KBr) 1587 cm)1(C=N). 1H NMR (500 MHz): d 3.05
Synthesis and antimicrobial activity of novel sulfone-linked bis (1H, dd, J = 7.5 Hz, J¢ = 17 Hz), d 3.78 (1H, dd, J = 12.5 Hz,
heterocycles. Eur J Med Chem;43:917–924. J¢ = 17 Hz), d 3.89 (3H, s), d 3.97 (3H, s), d 5.18 (1H, dd,
15. Chimenti F., Bizzarri B., Manna F., Bolasco A., Secci D., Chimenti J = 7.5 Hz, J¢ = 12.5 Hz), d 6.77–6.83 (2H, m), d 7.00–7.03 (3H,
P., Granese A., Rivanera D., Lilli D., Scaltrito M.M., Brenciaglia m), d 7.16–7.19 (2H, m), d 7.23–7.30 (4H, m), d 7.48 (1H, d,
M.I. (2005) Synthesis and in vitro selective anti-Helicobacter J = 1.5 Hz). 13C NMR (500 MHz): d 43.65, 55.95, 63.92, 108.14,
pylori activity of pyrazoline derivatives. Bioorg Med Chem 110.67, 113.33, 119.12, 119.19, 125.41, 125.28, 127.36, 128.79,
Lett;15:603–607. 128.96, 129.09, 129.32, 129.43, 129.96, 133.28, 141.20, 144.89,
16. vila H.P., Smnia E.F.A., Monache F.D., Jfflnior A.S. (2008) Struc- 146.91, 149.18, 150.03. HR-MS (m ⁄ z) for molecular formula
ture–activity relationship of antibacterial chalcones. Bioorg Med C23H21ClN2O2: calculated = 393.1373, found = 393.1370.
Chem;16:9790–9794. 22. Nielsen S.F., Boesen T., Larsen M., Schønning K., Kromann D.
17. Lin J., Rivett D.E., Wilshire J.F.K. (1977) The preparation and (2004) Antibacterial chalcones – bioisosteric replacement of the
photochemical properties of some 1,3-diphenyl-2-pyrazolines 4¢-hydroxy group. Bioorg Med Chem;12:3047–3054.
containing a heteroaromatic substituent. Aust J Chem;30:629– 23. Liu X.L., Xu Y.J., Go M.L. (2008) Functionalized chalcones
637. with basic functionalities have antibacterial activity against drug
18. Candan F., Unlu M., Tepe B., Daferera D., Polissiou M., Sokmen sensitive Staphylococcus aureus. Eur J Med Chem;43:1681–
A., Akpulat A. (2003) Antioxidant and antimicrobial activity of 1687.
the essential oil and methanol extracts of Achillea millefolium 24. Nowakowska Z. (2007) A review of anti-infective and anti-
subsp. millefolium Afan. (Asteraceae). J Ethnopharmacol;87:215– inflammatory chalcones. Eur J Med Chem;42:125–137.
220. 25. Ansari F.L., Baseer M., Iftikhar M., Kulsoom A., Ullah S., Nazir
19. Sarker S. D., Nahar L., Kumarasamy Y. (2007) Microtitre plate- A., Shaukat I-ul-H, Mirza B. (2009) Microwave assisted synthe-
based antibacterial assay incorporating resazurin as an indicator sis, antibacterial activity against Bordetella bronchiseptica of a
of cell growth, and its application in the in vitro antibacterial library of 3¢-hydroxyaryl and heteroaryl chalcones and molecular
screening of phytochemicals. Methods;43:321–324. descriptors-based SAR. ARKIVOC;X:318–332.
20. Charles E.S., Agrawal V.K., Sharma S., Iyer R.N. (1979) Synthesis 26. Bhatia N.M., Mahadik K.R., Bhatia M.S. (2009) QSAR analy-
of 2,5disubstituted benzimidazoles as potential antihookworm sis of 1,3-diaryl-2-propen-1-ones and their indole analogs
and antimicrobial agents. Eur J Med Chem Chim Ther;14:435– for designing potent antibacterial agents. Chem Pap;63:456–
438. 463.
21. Spectral data for compound PMS -10: FTIR (KBr) 27. Munawar M.A., Azad M., Athar M., Groundwater P.W. (2008)
1665 cm)1(C=O). 1H NMR (500 MHz): d 7.12 (1H, d, Synthesis and antimicrobial activity of quinoline-based 2-pyrazo-
J = 16 Hz), d 7.34–7.37 (3H, m), d 7.40 (1H, s), d 7.42 (1H, d, lines. Chem Pap;62:288–293.
J = 1.5 Hz), d 7.43–7.44 (2H, m), d 7.46–7.49 (3H, m). 13C NMR
(500 MHz): d193.41, 144.48, 138.95, 136.80, 132.94, 131.57, Note
131.31, 130.33, 129.71, 129.68, 129.40, 129.37, 129.29, 126.92,
a
126.63. HR-MS (m ⁄ z) for molecular formula C15H10Cl2O: calcu- [Link] [accessed on
lated = 277.0631, found = 277.0631. Spectral data for compound September 01 2010].

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