Synthesis and evaluation of new quinazolone derivatives of nalidixic acid as potential antibacterial and antifungal agents

Article abstract of DOI:10.1016/j.ejmech.2005.09.002

In continuation of our work on synthesis of biheterocycles carrying the biodynamic heterocyclic systems at position 3, a series of new nalidixic acid derivatives having quinazolones moiety were synthesised to achieve enhanced biological activity and wide spectrum of activity. Nalidixic Acid was first converted into its acid chloride using thionyl chloride as an acylating agent at laboratory temperature. Later it was converted to methyl ester. Nalidixoyl chloride formed vigorously reacts with methanol to give a methyl ester of nalidixic acid. The ester on addition of hydrazine hydrate furnished nalidixic acid hydrazide. Appropriate anthranilic acid was refluxed with acetic anhydride to form Benzoxazine/Acetanthranil. 5-iodo-derivative of anthranilic acid was prepared and also utilised to obtain 6-iodo-Benzoxazine/Acetanthranil. Also, 6-nitro-Benzoxazine/Acetanthranil was obtained by nitration of acetanthranil using conc. H₂SO₄ and fuming HNO₃. Equimolar proportions of the appropriate synthesised acetanthranils and nalidixic acid hydrazide in the presence of ethanol were refluxed to synthesise quinazolones. Elemental analysis and IR spectra confirmed nalidixic acid hydrazide formation. The structures of the compounds obtained have been established on the basis of Spectral (IR, ¹H NMR and mass) data. The current study also involves in vitro antimicrobial screening (using Agar dilution and Punch well diffusion method) of synthesised quinazolone derivatives bearing nalidixic acid moiety on randomly collected microbial strains. The derivatives Ga (NAH), Gb (QN) and Gd (NiQNA) showed marked inhibitory activity against enteric pathogen like Aeromonas hydrophila, a causative agent of diarrhoea in both children as well as adults. Among the respiratory pathogens included in study, derivative Gd (NiQNA) was found to be active against Streptococcus pyogenes. No significant inhibitory activity was seen by any of synthesised derivatives against Coagulase negative Staphylococcus. Derivative Ga (NAH) was found to show very high activity against the Candida colonies and derivative Gd (NiQNA) was also found to exhibit inhibitory activity against Candida albicans; a normal flora of the human body which plays an important role in causing opportunistic infections in immunocompromised hosts. Proteus vulgaris, a gram-negative bacteria included in our study was found to be inhibited by derivative Gb (QN).

Full text of DOI:10.1016/j.ejmech.2005.09.002

European Journal of Medicinal Chemistry 41 (2006) 256–262
http://france.elsevier.com/direct/ejmech
Short communication
Synthesis and evaluation of new quinazolone derivatives
of nalidixic acid as potential antibacterial and antifungal agents
Gaurav Grover a, Suvarna G. Kini b,*
a Clinical Research and Medical Services, LG Life Sciences India Pvt. Ltd., LG House, AB-3, Safdarjung Enclave, New Delhi 110069, India
b Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal 576119, Karnataka, India
Received 14 June 2004; received in revised form 31 August 2004; accepted 14 September 2005
Available online 02 November 2005
Abstract
In continuation of our work on synthesis of biheterocycles carrying the biodynamic heterocyclic systems at position 3, a series of new
nalidixic acid derivatives having quinazolones moiety were synthesised to achieve enhanced biological activity and wide spectrum of activity.
Nalidixic Acid was first converted into its acid chloride using thionyl chloride as an acylating agent at laboratory temperature. Later it was
converted to methyl ester. Nalidixoyl chloride formed vigorously reacts with methanol to give a methyl ester of nalidixic acid. The ester on
addition of hydrazine hydrate furnished nalidixic acid hydrazide. Appropriate anthranilic acid was refluxed with acetic anhydride to form Ben-
zoxazine/Acetanthranil. 5-iodo-derivative of anthranilic acid was prepared and also utilised to obtain 6-iodo-Benzoxazine/Acetanthranil. Also, 6-
nitro-Benzoxazine/Acetanthranil was obtained by nitration of acetanthranil using conc. H2SO4 and fuming HNO3. Equimolar proportions of the
appropriate synthesised acetanthranils and nalidixic acid hydrazide in the presence of ethanol were refluxed to synthesise quinazolones. Elemen-
tal analysis and IR spectra confirmed nalidixic acid hydrazide formation. The structures of the compounds obtained have been established on the
1
basis of Spectral (IR, H NMR and mass) data. The current study also involves in vitro antimicrobial screening (using Agar dilution and Punch
well diffusion method) of synthesised quinazolone derivatives bearing nalidixic acid moiety on randomly collected microbial strains. The deri-
vatives Ga (NAH), Gb (QN) and Gd (NiQNA) showed marked inhibitory activity against enteric pathogen like Aeromonas hydrophila, a
causative agent of diarrhoea in both children as well as adults. Among the respiratory pathogens included in study, derivative Gd (NiQNA)
was found to be active against Streptococcus pyogenes. No significant inhibitory activity was seen by any of synthesised derivatives against
Coagulase negative Staphylococcus. Derivative Ga (NAH) was found to show very high activity against the Candida colonies and derivative Gd
(NiQNA) was also found to exhibit inhibitory activity against Candida albicans; a normal flora of the human body which plays an important role
in causing opportunistic infections in immunocompromised hosts. Proteus vulgaris, a gram-negative bacteria included in our study was found to
be inhibited by derivative Gb (QN).
© 2005 Elsevier SAS. All rights reserved.
Keywords: Proteus vulgaris; Streptococcus pyogenes; Candida albicans; Aeromonas hydrophila; Coagulase negative Staphylococcus; Nalidixic acid hydrazide
(NAH); Quinazolinone derivative of nalidixic acid (QN); Iodo-quinazolinone derivative of nalidixic acid (IQN); Nitro-quinazolinone derivatives of nalidixic acid
(NIQNA); Urinary tract infections
1. Introduction
or potential administration but got concentrated in the urine,
where they could be effective for eradicating urinary tract in-
fections.
Nalidixic acid (1,8-naphthyridine derivative) was intro-
duced for the treatment of urinary tract infections in 1963. It
failed to achieve adequate concentrations in the plasma or
tissues for the treatment of systemic infections following oral
Structure activity relationship (SAR) of compounds based
on nalidixic acid have led to a large group of synthetic anti-
bacterial agents collectively known as the quinolones [1]. Re-
sistance was found to emerge rapidly, even while on therapy.
These agents inhibit DNA synthesis during bacterial replica-
tion. This effect may result from interference with DNA gyrase
activity [2].
* Corresponding author.
E-mail address: suvarna.gk@manipal.edu (S.G. Kini).
0223-5234/$ - see front matter © 2005 Elsevier SAS. All rights reserved.
doi:10.1016/j.ejmech.2005.09.002

G. Grover, S.G. Kini / European Journal of Medicinal Chemistry 41 (2006) 256–262
257
Nalidixic acid is known to be effective against indole posi-
tive Proteus in urinary tract infections. Failure observed in pa-
tients may be due to reinfection from the prostate gland [2].
Nalidixic acid is particularly active against the majority of
gram-negative organisms that infect urinary tract especially
E. coli. It is often effective against other coliform bacteria such
as Klebsiella and Enterobacter aerogenosa. Brucella species
and some strains of Salmonella and Shigella are also sensitive.
However, most Pseudomonas sp. are resistant to nalidixic acid.
This drug is ineffective against gram-positive bacteria includ-
ing Staphylococcus and Enterococcus fecalis (formerly, Strep-
tococcus fecalis). Studies have indicated that nalidixic acid is
effective against 99% strains of E. coli, 98% of P. mirabilis,
92% of Klebsiella and Enterobacter and 80% of other coliform
species [3].
1,8-Naphthyridines possess diverse biological activities and
there are numerous reports that highlight their chemistry and
use. They are also found to possess interesting antibacterial
activity.
Quinazolones have been reported to have wide-ranging bio-
logical activities including antitubercular [4], fungicidal [5],
antimalarial [6], anticancer and anti-HIV agents [6], antiviral
[7] and antibacterial activity [8].
Structural variations bring about new physical and biologi-
cal properties. The molecular manipulation of a promising lead
compound is still a major line of approach for the discovery of
new drugs. Molecular manipulation involves the efforts to
combine separate groups having similar activity in one com-
pound by eliminating or substituting new moiety to a parent
lead compound.
In the present work, antimicrobial activity associated with
both quinazolines and nalidixic acid moieties prompted us to
synthesise some nalidixic acid derivatives carrying the biody-
namic heterocyclic systems (quinazolones) at position-3 with
an objective to obtain biheterocycles of enhanced biological
activities. The compounds so obtained were screened for anti-
fungal and antibacterial activities.
series of petriplates were prepared with increasing concentra-
tions of the drug. With the help of inoculating applicator, as
many as 14 different strains were spot inoculated on each plate.
After overnight incubation, minimum inhibitory concentration
(MIC) end point was determined by placing plate against a
dark background and observing the lowest concentration of de-
rivatives inhibiting visible growth. The MIC of each derivative
was recorded in μg ml–1. Wherever two or more colonies per-
sisted beyond the end point or growth was present in higher
concentration and not in lower concentration, the test was re-
peated.
2.2. The punch well/cup plate diffusion method
In this technique petridishes of agar medium plate were pre-
pared by pouring melted agar inoculated with a variety of mi-
croorganisms. After the agar settled, cups were made in the
agar petridishes. Test solutions were prepared using the follow-
ing concentrations based on results obtained in agar dilution
method.
Derivative Ga (NAH) in concentrations of 30, 100, 200,
300 μg ml–1, derivative Gb (QN) in concentrations of 50,
100, 150, 200, 250, 300 μg ml–1, derivative Gc (IQN) in con-
centrations of 20, 40, 60, 80, 100 μg ml–1, derivative Gd
(NiQNA) in concentrations of 50 100, 150, 200, 250,
300 μg ml–1 were made.
Isolates of clinically obtained strains used are mentioned
below:
● Aeromonas hydrophila, Escherichia coli, Klebsiella aero-
genes, Enterococci (COPS) Coagulase positive Staphylo-
coccus aureus (CONS) Coagulase negative Staphylococcus,
Streptococcus pyogenes, Candida albicans, Salmonella ty-
phimurium, Shigella flexneri, Vibrio cholerae, Acinetobac-
ter sp., Proteus vulgaris.
All the derivatives were compared with Ampicillin, nali-
dixic acid and Fluconazole for antibacterial and antifungal ac-
tivity.
2. Antimicrobial screening [9]
All the synthesised quinazolone derivatives of nalidixic acid
were screened for antimicrobial activity using the following
methods.
3. Results
The derivatives showed marked activity against
A. hydrophila, C. negative Staphylococcus, S. pyogenes,
C. albicans, and P. vulgaris with agar dilution method (see
Tables 1–2). Only those strains, which were found to be sus-
ceptible to the test derivatives, have been utilised for cup plate
diffusion method and the results are included in Tables 3–5.
Derivative Ga (NAH), Gb (QN) and Gd (NiQNA) are
found to have good inhibitory effect at concentrations of 300,
200 and 200 μg ml–1, respectively; on one of the enteric patho-
gen A. hydrophila, the causative agent of diarrhoea in both
adults and children (see Table 3).
2.1. Agar dilution method
Reference preparations of quinazolone derivatives of nali-
dixic acid were prepared in diluent DMSO (Dimethyl Sulph-
oxide) at 10 × concentrations, starting with a stock concentra-
tion of 30 and 600 μg ml–1 and covered a full range of 30–
600 μg ml–1. This method was convenient and economical on
pipette use. MHA (Muller Hinton Agar) was used as a medium
for bacterial screening [9] whereas SDA (Sabouraud’s Dex-
trose Agar) Broth was used for fungal screening. Study deriva-
tives were incorporated into liquefied agar medium at 45–50 °
C, mixed and poured in petridishes and allowed to solidify. A
Among the respiratory pathogens included in our study, de-
rivative Gd (NiQNA) is found to have high activity against
S. pyogenes at 300 μg ml–1 (see Table 3).

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G. Grover, S.G. Kini / European Journal of Medicinal Chemistry 41 (2006) 256–262
Table 1
Agar dilution method results of synthesised new derivatives of nalidixic acid
Strain used
Derivative (NAH) Ga
Ampicillin
Derivative (QN) Gb
Concentrations in μg ml–1
Concentrations in μg ml–1
30
−
−
−
−
−
−
−
−
−
−
−
−
−
100
+
−
−
−
−
−
+
−
−
−
−
−
200
−
−
−
−
−
+
+
+
−
−
−
−
300
+
−
−
−
−
−
+
+
−
−
−
−
10
+
+
+
+
+
+
+
+
−
−
−
−
−
50
+
−
−
−
−
−
−
−
−
−
−
−
−
100
+
−
−
−
−
−
−
−
−
−
−
−
150
+
−
−
−
−
−
−
−
−
−
−
−
200
+
−
−
−
−
−
−
−
−
−
−
−
250
+
−
−
−
−
−
−
−
−
−
−
−
300
+
−
−
−
−
−
−
−
−
−
−
−
A. hydrophila
E. coli
K. aerogenes
Enterococi
S. aureus
C. negative Staphylococcus
Streptococcus
C. albicans
S. typhimurium
S. flexneri
V. cholerae
Acenitobacter sp.
P. vulgaris
−
−
−
−
+
+
−
−
(−) Represents no inhibition of growth/resistant; (+) represents inhibition of growth/susceptible.
Table 2
Agar dilution method results of synthesised new derivatives of nalidixic acid
Strain used
Derivative (IQN) Gc
Ampicillin
Derivative (NIQNA) Gd
concentrations in μg ml–1
concentrations in μg ml–1
20
−
−
−
−
−
−
−
−
−
−
−
−
−
40
−
−
−
−
−
−
−
+
−
−
−
−
−
60
−
−
−
−
−
−
−
+
−
−
−
−
−
80
−
−
−
−
−
−
−
+
−
−
−
−
−
100
−
−
−
−
−
−
−
−
−
−
−
−
10
+
+
+
+
+
+
+
+
+
+
+
+
+
50
+
−
−
−
−
−
+
+
−
−
−
−
−
100
+
−
−
−
−
−
+
+
−
−
−
−
150
+
−
−
−
−
−
+
+
−
−
−
−
200
+
−
−
−
−
−
+
+
−
−
−
−
250
+
−
−
−
−
−
+
+
−
−
−
−
300
A. hydrophila
E. coli
+
−
−
−
−
−
+
+
−
−
−
−
−
Klebsiella aerogenes
Enterococi
Coagulase positive Staphylococcus aureus
C. negative Staphylococcus
Streptococcus
C. albicans
S. typhimurium
S. flexneri
V. cholerae
Acenitobacter sp.
P. vulgaris
−
−
−
−
−
Table 3
Punch well/cup plate diffusion method results of synthesised new derivatives of nalidixic acid

G. Grover, S.G. Kini / European Journal of Medicinal Chemistry 41 (2006) 256–262
259
Table 4
Punch well/cup plate diffusion method results of synthesised new derivatives of nalidixic acid
Table 5
Punch well/cup plate diffusion method results of synthesised new derivatives of nalidixic acid
Derivative Ga (NAH) shows inhibition zone of 7 mm at
300 μg ml–1 against C. negative Staphylococcus that is insuffi-
cient to inhibit the growth appreciably (see Table 4).
Derivative Ga (NAH) shows very high activity at
300 μg ml–1 comparable to standard drug Fluconazole
(25 μg ml–1) against C. albicans. It also has moderate activity
at concentrations of 30, 100, 200 μg ml–1. Derivatives Gc
(IQN) and Gd (NiQNA) are found to have moderate activity
against C. albicans at almost all concentrations studied (see
Table 4).
4. Experimental section
4.1. General
Nalidixic acid was obtained as a gift sample from CFL
Pharma Limited, Curti, Ponda, Goa. All the melting points
are uncorrected and were recorded in a Toshniwal melting
point apparatus. TLC was carried out using Silica gel G pro-
cured from Merck. Solvent used was Chloroform: Acetone
(4:1). Nitrogen % estimation was carried out for nalidixic acid
Hydrazide by RSIC, CDRI, Lucknow. UV spectra were re-
corded on UV–Visible spectrometer (Shimadzu 160 IPC). IR
Gram negative bacteria P. vulgaris is inhibited by derivative
Gb (QN) at 150 μg ml (see Table 5).

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G. Grover, S.G. Kini / European Journal of Medicinal Chemistry 41 (2006) 256–262
spectra of the compounds were recorded using KBr pellet
method on an FTIR-8300 Shimadzu spectrophotometer. All
the chemicals and reagents that where used were obtained in
high quality. Mass spectra were provided by RSIC, IIT Ma-
dras, and were acquired on a MASSPEC system (msw/9629).
H1NMR was done on Instrument Joel Model: GSX 400.
chloride was added and closed in fuming cupboard chamber.
The flask was kept aside for 15 min. Later 2 ml of methanol
was added to the solution in the round bottom flask drop by
drop and mixed thoroughly after each addition. The reaction
should be carried out carefully in fuming cupboard chamber.
The Nalidixoyl chloride formed, in situ, by the addition of
Thionyl chloride to nalidixic acid reacted with methanol and
was kept for refluxing. Time taken for complete conversion
was 1 hour. This formed nalidixic acid ester.
4.3. Formation of nalidixic acid hydrazide
[derivative Ga (NAH)] [10]
To the above formed methyl ester in solution, 2 ml of Hy-
drazine hydrate was added drop wise carefully through the side
of the round bottom flask kept closed in fuming cupboard
chamber. Evolution of heat took place with a violent reaction.
The above mixture was then kept for refluxing for 4 hours. The
contents of the flask were poured into a beaker containing ice
cold water. A yellowish-orange coloured nalidixic acid hydra-
zide precipitated immediately.
4.4. Preparation of acetanthranil [11]
Appropriate anthranilic acid of weight 6.8 g (0.05 mol) was
refluxed with 20 ml (0.21 mol) acetic anhydride for 1 hour.
After excess acetic anhydride was distilled, the acetanthranil
separated as solid mass and was used without further purifica-
tion.
4.5. Preparation of 6-nitro-acetanthranil [12]
To 2-methyl-3,1-benzoxazine-4-one (6 g) dissolved in conc.
Sulphuric acid (20 ml), was added fuming nitric acid (10 ml)
keeping temperature below 75 °C. The reaction mixture was
poured on ice (200 g), filtered, washed and recrystallised from
glacial acetic acid (95%).
4.6. Preparation of 6-iodo-acetanthranil
Characterisation data of compounds Ga–Gd
Compound
Molecular
weight
Nitrogen % Melting
Rf
Molecular
formula
This involves mainly two steps:
found
Point (° C)
(Calc.)
● Formation of Iodide derivative of anthranilic acid (Based on
method developed by Klemme Carl J. and Hunter James H.,
November 16, 1940).
Derivative
Ga (NAH)
Derivative
Gb (QN)
Derivative
Gc (IQN)
Derivative
Gd
246
375
501
521
22.9 (22.7) 218
0.46 C12H14N4O2
0.36 C21H19N5O2
180
184
271
With magnetic stirrer 5 g (0.184 mol) of recrystallised an-
thranilic acid (m.p. 145°) was dissolved in a solution of
3.38 g of stick potassium hydroxide in 100 cm3 of water
contained in 500 ml beaker. A solution of 9.3 g
(0.184 mol) of Iodine in 50 cm3 of water containing
4.95 g of stick potassium hydroxide was slowly run into a
well-stirred potassium anthranilate solution. After 1 min,
20 cm3 of Glacial acetic acid was quickly added and the
reaction-mixture immediately diluted with 100 cm3 of
water. A dark precipitate began to appear almost at once;
stirring was continued for 1 hour, during which time this
0.37 C21H19N5-
O2I
0.44
C21H18N6O4
(NiQNA)
4.2. Preparation of nalidixic acid ester via nalidixoyl chloride
from nalidixic acid [11]
1 g of pure nalidixic acid was accurately weighed into a
250 ml dry, clean, round bottom flask and 2 ml of thionyl

G. Grover, S.G. Kini / European Journal of Medicinal Chemistry 41 (2006) 256–262
261
precipitate assumed a light brown colour. After standing un-
5.3. Derivative Gc (IQN)
disturbed for 2 hours, excess iodine was removed by adding
5 cm3 of 15% sodium bisulfite and thoroughly agitating.
The mixture was allowed to stand a short while. The preci-
pitate was collected, repeatedly washed with water and air-
dried. Yield of crude product 8 g (86.8%).
UV (MeOH): 325, 259, 225; IR (KBr): 3234 cm–1 (–N–H),
1683 cm–1 (–C=O), 156 cm–1 (–N–C=O), 1598 cm–1 (–C=O),
1498 cm−1 (–C=N), 1375 cm–1 (C–N stretch tertiary),
962 cm–1 (CH deformation aromatic), 478 cm–1 (C–I); 1H
NMR (DMSO): 8 (MHz) (1 proton, CONH–), 7–8(MHz)
(6H aromatic protons), 2(MHz) (CH3, 3H aliphatic), 2(MHz)
(CH3, 3H aliphatic), 1(MHz) (C2H5, 5H aliphatic); MS: m/z
472 (M+, 1%), 263 (100%), 215 (28%), 187 (24%), 160
(8%), 119 (26%), 91 (26%).
● Acetanthranil formation by refluxing with acetic anhydride.
[12].
Appropriate 2-amino-5-iodobenzoic acid 3.2 g (0.0125 mol)
was refluxed with acetic anhydride 10 ml (0.106 mol) for
one and half-hour. After excess of acetic anhydride was dis-
tilled, the 5-iodoacetanthranil was separated as brown co-
loured crystalline product and was used without purification.
5.4. Derivative Gd (NiQNA)
4.7. Quinazolones preparation
UV (MeOH): 325, 256, 217, 203; IR (KBr):
3419 cm–1 (–NH–), 2970 cm–1 (–CH), 1610 cm–1 (CONH),
1517 cm–1 (–C=N), 1442 cm–1 (–NO2), 1334 cm–1 (C–N
stretch tertiary).
Equimolar proportions of the appropriate acetanthranils and
nalidixic acid hydrazide in the presence of ethanol were heated
under reflux for 8 hours to synthesise quinazolones [13].
4.7.1. Preparation of 2-methyl-3,1-quinazol-4-one derivatives
of nalidixic acid [derivative Gb (QN)]
6. Discussion
Interaction of 2-methyl-3, 1-benzoxazine-4-one with nali-
dixic acid hydrazide yielded dark orange brown coloured crys-
tals of 3-N-(nalidixic amide)-2-methyl-3,1-quinazol-4-one.
In a previous study, certain new nalidixic acid derivatives
substituted with 1,2 pyrazolines were synthesised by Waheed
and Khan [14] and showed antibacterial and analgesic activity.
However, the present study is the first of its type, involving
synthesis of quinazolone derivatives of nalidixic acid and
screening for antibacterial and antifungal activity using 14
clinically isolated microbial strains.
4.7.2. 6-Iodo-2-methyl-3,1-quinazol-4-one derivatives
of nalidixic acid [derivative Gc (IQN)]
Interaction of 2-methyl-6-iodo-3, 1-benzoxazine-4-one and
nalidixic acid hydrazide yielded 6-iodo-2-methyl-3,1-quina-
zol-4-one derivatives of nalidixic acid. The product was ob-
tained as flaky mass and was allowed to dry overnight.
The antibacterial activity data indicate that certain synthe-
sised derivatives, e.g. derivatives Ga (NAH), Gb (QN) and
Gd (NiQNA) exhibited inhibitory activity against
A. hydrophila, which was resistant to pure nalidixic acid. Simi-
larly, derivative Ga (NAH) and Gd (NiQNA) showed inhibi-
tory activity against S. pyogenes, which was also resistant to
pure nalidixic acid. However, no inhibitory activity was ob-
served against C. negative Staphylococcus with both synthe-
sised quinazolone derivatives and pure nalidixic acid.
4.7.3. 6-Nitro-2-methyl-3,1-quinazol-4-one derivatives
of nalidixic acid [derivative Gd (NiQNA)]
Interaction of the appropriate 2-methyl-6-Nitro-3, 1-benzox-
azine-4-one and nalidixic acid hydrazide yielded 6-nitro-2-
methyl-3,1-quinazol-4-one derivatives of nalidixic acid.
Quinazolone ring substituted nalidixic acid moiety showed
an inhibitory activity against C. albicans, which was found to
be absent in the parent lead compound (pure nalidixic acid). A
decreased inhibitory activity against P. vulgaris was noted in
synthesised quinazolone derivatives of nalidixic acid as com-
pared to pure nalidixic acid. Almost all the synthesised deriva-
tives have displayed enhanced antimicrobial activity in com-
parison to pure nalidixic acid.
5. Spectral data
5.1. Derivative Ga (NAH)
UV (MeOH): 322, 254, 216; IR (KBr): 3309 cm–1(amide
NH bonded), 3232 cm–1 (Primary aromatic NH free),
3051 cm–1 (Aromatic –CH stretch), 1612 cm–1 (–C=O),
1496 cm–1 (Aromatic C=C), 1359 cm–1 (C–N stretch tertiary),
981 cm–1 (–CH deformation aromatic).
Acknowledgments
5.2. Derivative Gb (QN)
The authors wish to thank Dr. Mamta Ballal, Kasturba Med-
ical College, Manipal for the antimicrobial screening, RSIC,
CDRI, Lucknow for the Nitrogen Elemental analysis and
RSIC, IIT Madras, Chennai for MS and 1H NMR of the
synthesised compounds.
UV (MeOH): 304, 251, 220, 194; IR (KBr): 3182 cm–1
(–NH–), 1691 cm–1 (–C=O) 1651 cm–1 (–N–C=O),
1595 cm–1 (–C=O), 1517 cm–1 (–C=N), 1375 cm–1 (C–N
stretch tertiary), 962 (CH deformation aromatic).

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G. Grover, S.G. Kini / European Journal of Medicinal Chemistry 41 (2006) 256–262
[8] N.B. Patel, J.D. Lilakar, Synthesis of new substituted-4-(3H)-quinazoli-
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