Novel benzopyranopyridine derivatives of 2-amino-3-formylchromone

Article abstract of DOI:10.2478/s11696-010-0072-0

Enol lactones such as 4-hydroxy-6-methyl-2H-pyran-2-one (triacetic acid lactone, TAL) and 4-hydroxycoumarin when treated with 2-amino-3-formylchromone under basic conditions afforded 3-acetoacetyl benzopyranopyridones and benzopyranopyridines, respectively. A series of pyrazole derivatives was prepared by the reaction of 3-acetoacetyl benzopyranopyridones with different hydrazines. All compounds were characterised on the basis of spectral data and their antibacterial activity evaluated.

Full text of DOI:10.2478/s11696-010-0072-0

Chemical Papers 64 (6) 818–824 (2010)
DOI: 10.2478/s11696-010-0072-0
ORIGINAL PAPER
Novel benzopyranopyridine derivatives
of 2-amino-3-formylchromone
Zeba Nafees Siddiqui*, Shagufta Praveen, Farheen Farooq
Department of Chemistry, Aligarh Muslim University, Aligarh-202002, India
Received 11 February 2010; Revised 28 June 2010; Accepted 7 July 2010
Enol lactones such as 4-hydroxy-6-methyl-2H-pyran-2-one (triacetic acid lactone, TAL) and 4-
hydroxycoumarin when treated with 2-amino-3-formylchromone under basic conditions afforded
3-acetoacetyl benzopyranopyridones and benzopyranopyridines, respectively. A series of pyrazole
derivatives was prepared by the reaction of 3-acetoacetyl benzopyranopyridones with different hy-
drazines. All compounds were characterised on the basis of spectral data and their antibacterial
activity evaluated.
c
ꢀ 2010 Institute of Chemistry, Slovak Academy of Sciences
Keywords: 2-amino-3-formylchromone, 4-hydroxycoumarin, pyranopyridines, antibacterial
Introduction
Some pyridobenzopyranones have also been reported
as herbicide safeners (Hagen et al., 1992).
Benzopyranopyridine derivatives are of scientific
value because they exhibit various biological activi-
ties. They have been reported to exhibit potent bron-
chiodilating activity in the treatment of bronchitis and
asthma (Connor et al., 1984). This class of compounds
has also shown potential selectivity towards leukaemic
cell lines (El-Subbagh et al., 2000). Therefore, syn-
thesis of this condensed heterocyclic system is worth-
while because of its important biological properties
such as antiallergic (Nohara et al., 1985), antiangio-
genic (Lee et al., 2005), antirheumatic (Evdokimov et
al., 2006), antibacterial (Srivastava et al., 2005), anti-
inflammatory and analgesic (Hosni & Abdulla, 2008),
antagonism towards the antipsychotic dopamine D4
receptor (Unangst et al., 1997), neurogenic disorders
such as Alzheimer’s disease, Parkinson’s disease, de-
pression, allergic responses, sedation (Borroni et al.,
2001), being the properties associated with the struc-
ture of these compounds. Ever since establishment of
the structure-activity relationship of cromakalim as a
potent anti-hypertensive agent, other examples such
as EMD52692 and Ro 31-6930 have been reported
(Ashwood et al., 1986, 1991; Cecchetti et al., 2006;
Bergmann & Gericke, 1990; Paciorek et al., 1990).
On the other hand, pyrazole skeleton is found in
a large number of naturally occurring or synthetic
biologically-active heterocyclic compounds (Singh et
al., 2006). Pyrazole derivatives have been used as
analgesic (Prokopp et al., 2006), anti-inflammatory
(Patel et al., 2004), antipyretic (Shchegoľkov et al.,
2006), antidepressant (Bailey et al., 1985), antibacte-
rial (Dardari et al., 2006), antimicrobial (Wardakhan
& Louca, 2007), and anti-convulsant (Chauhan et al.,
1993) agents. They are also applied as herbicides (Vi-
centini et al., 2005) and fungicides (Vors et al., 2003)
used in sunscreen materials (García et al., 1991) and
as analytical reagents (Busev et al., 1965).
Motivated by the above findings, and as a part
of our continuing study on the functionalisation of
pyranopyridines (Siddiqui et al., 2006) and pyra-
nocoumarines (Siddiqui & Asad, 2006), we looked
into designing and synthesising new pyranopyridines
and their derivatives containing a pyrazole moiety,
which might show much better or different biolog-
ical properties. Hence, the present study describes
the synthesis and antibacterial examination of 3-
acetoacetyl benzopyranopyridones (Vb), pentacyclic
benzopyranopyridines (VIIIa and VIIIb), and pyra-
*Corresponding author, e-mail: zns.siddiqui@gmail.com

Z. N. Siddiqui et al./Chemical Papers 64 (6) 818–824 (2010)
Table 1. Characteristics of newly prepared compounds
819
wi(calc.)/%
wi(found)/%
Yield
M.p.
Compound
Formula
Mr
C
H
N
S
–
–
–
–
–
%
80
42
19
71
60
64
65
71
70
◦C
196
283
292
300d
280
300d
244
251
260
Vb
C17H13NO5
C19H9NO4
311.29
315.28
315.28
293.27
369.37
426.45
307.30
383.40
440.41
65.59
65.63
4.20
4.23
4.50
4.52
VIIIa
VIIIb
IXa
IXb
IXc
IXd
IXe
IXf
72.38
72.41
2.87
2.84
4.44
4.39
C19H9NO4
72.38
72.32
2.87
2.82
4.44
4.45
C16H11N3O3
C22H15N3O3
C23H14N4O3S
65.53
65.58
3.78
3.82
14.33
14.37
71.53
71.57
4.09
4.06
11.37
11.40
64.78
64.82
3.31
3.29
13.14
13.19
7.52
7.55
C
17H13N3O3
66.44
66.47
4.26
4.23
13.67
13.69
–
C23H17N3O3
72.05
72.09
4.47
4.42
10.96
10.94
–
C24H16N4O3S
65.44
65.49
3.66
3.62
12.72
12.75
7.28
7.32
zolylpyranopyridines (IXa–IXf ) resulting from the re-
action of 2-amino-3-formylchromone (IIIa and IIIb)
and enol lactones (triacetic acid lactone IV and 4-
hydroxycoumarin VI ).
piperidine (10.5 mmol) and triacetic acid lactone IV
(7.94 mmol). The reaction mixture was kept at room
temperature for 7 days. The product Vb, which crys-
tallised from the solution as a canary yellow solid,
was filtered, washed with cold water, and dried. The
mother liquor was poured into the ice-cold water and
acidified with HCl. The solid precipitated, was fil-
tered, washed with water, dried and re-crystallised
from chloroform–methanol mixture to yield more Vb.
The total yield was 1.22 g (3.91 mmol).
Experimental
Melting points were measured in a digital melt-
ing point apparatus (Macro Scientific Works (Regd.)
MSW-401 Delhi, India). IR spectra were recorded on
a Perkin–Elmer RXI spectrometer (UK) in KBr and
only noteworthy absorptions are listed. 1H NMR spec-
tra were recorded on a Bruker DRX300 spectrometer
(Switzerland) using tetramethylsilane (TMS) as inter-
nal standard and DMSO-d6/CDCl3 as solvent. Mass
spectra were obtained on a Jeol-SX-102 (FAB) spec-
trometer (Japan). Elemental analysis was performed
on Elementar Vario EL III (Germany) and results
agreed favourably with calculated values. IIIa, IIIb,
IV, Va compounds, and hydrazinobenzothiazole were
prepared according to a procedure reported by (Pe-
tersen & Heitzer, 1976; Butt & Elvidge, 1963; Siddiqui
et al., 2006; Singh et al., 1990). 4-Hydroxycoumarin,
hydrazine hydrate, phenylhydrazine, methanol, pyri-
dine, and piperidine were obtained from Otto-kemi
Pvt. Ltd. (Mumbai, India). Physicochemical and spec-
tral data of the newly synthesised compounds are
given in Tables 1 and 2, respectively.
4-Oxo-4H-1-benzopyrano[2,3:2,3]pyrido[3,2-b]-
4-oxo-4H-1-benzopyran-4-one (VIIIa) and
4-oxo-4H-1-benzopyrano[2,3:2,3]pyrido[2,3-c]-
2-oxo-2H-1-benzopyran-2-one (VIIIb)
A mixture of 2-amino-3-formylchromone, IIIa (5.29
mmol) and 4-hydroxycoumarin, VI (5.29 mmol) in
methanol (20 mL) containing a catalytic quantity
of pyridine (0.05 mL) was heated under reflux in a
water bath for 12 h. After completion of the reac-
tion (checked by TLC), the compound, kept at room
temperature, was allowed to precipitate to produce
a yellowish-brown solid. The precipitate was filtered,
washed thoroughly with methanol and allowed to pass
through a column filled with silica gel. The elution
of the column with petrol–benzene mixture (ϕpetrol
= 0.6) afforded a yellow compound VIIIa (Schurreit,
1987) which was re-crystallised from chloroform as yel-
low crystals. Further elution of the column with petrol
and benzene (ϕr = 0.5) gave a light yellow solid VIIIb
(Schurreit, 1987). It was re-crystallised from chloro-
form as light yellow crystals. The yield of VIIIa was
0.69 g (2.18 mmol) and VIIIb 0.31 g (0.983 mmol).
3-Acetoacetyl-7-methyl-5-oxo-5H-
[1]benzopyrano[3,2-e]pyridin-2-one (Vb)
2-Amino-3-formyl-6-methylchromone IIIb (4.93
mmol) was dissolved in pyridine (30 mL) containing

820
Z. N. Siddiqui et al./Chemical Papers 64 (6) 818–824 (2010)
Table 2. Spectral data of newly prepared compounds
Compound
Spectral data
Vb
IR, ν˜/cm−1: 3445 (NH), 1668, 1649, 1618 (C O)
—
—
1H NMR (CDCl3), δ: 2.24 (s, 3H, CH3), 2.49 (s, 3H, CH3), 6.40 (s, 1H, Ha), 7.59 (m, 2H, H-8, H-9), 8.08 (s, 1H,
H-6), 9.04 (s, 1H, Hb), 14.58 (br s, 1H, OH, D2O exchangeable)
MS, m/z (Ir/%): 311 (100) (M+), 294, 267, 254, 253
IR, ν˜/cm−1: 1670, 1665 (C O)
—
VIIIa
—
1H NMR (CDCl3), δ: 7.87 (m, 6H, Ar-H), 8.32 (d, 1H, J = 7.8 Hz, H-4), 8.61 (d, 1H, J = 7.5 Hz, H-8), 9.59 (s, 1H,
H-6)
MS, m/z (Ir/%): 315 (60) (M+), 259, 195, 167, 120
IR, ν˜/cm−1: 1751, 1671 (C O)
—
VIIIb
IXa
—
1H NMR (CDCl3), δ: 7.86 (m, 7H, Ar-H), 8.37 (d, 1 H, J = 7.8 Hz, H-4), 9.71 (s, 1H, H-6)
MS, m/z (Ir/%): 315 (100) (M+), 287, 271, 259, 243, 195, 166, 120
IR, ν˜/cm−1: 3412 (NH), 1664, 1620 (C O), 1608 (C C), 1569 (CN)
—
—
—
—
1H NMR (DMSO-d6), δ: 2.27 (s, 3H, CH3), 6.71 (s, 1H, H-4ꢀ), 7.87 (m, 4H, Ar-H, H-4), 8.17 (dd, 1H, J = 7.8 Hz,
3Hz, H-6), 8.69 (br s, 2H, NH, D2O exchangeable)
MS, m/z (Ir/%): 293 (50) (M+), 278, 156, 155, 137, 135, 105
—
—
IXb
IXc
IXd
IXe
IXf
IR, ν˜/cm−1: 3428 (NH), 1638 (C O), 1610 (C C), 1575 (CN)
—
—
1H NMR (DMSO-d6), δ: 2.25 (s, 3H, CH3), 6.24 (s, 1H, H-4ꢀ), 7.68 (m, 9H, Ar-H, H-4), 7.98 (dd, 1H, J = 7.8 Hz,
1.5 Hz, H-6)
MS, m/z (Ir/%): 369 (58) (M+), 368, 353, 155, 91
IR, ν˜/cm−1: 3400 (NH), 1656, 1637 (C O), 1610 (C C), 1590 (CN)
—
—
—
—
1H NMR (DMSO-d6), δ: 2.11 (s, 3H, CH3), 7.88 (m, 9H, Ar-H, H-4, H4ꢀ), 8.20 (d, J = 8.1 Hz, H-6), 8.64 (br s, 1H,
NH, D2O exchangeable)
MS, m/z (Ir/%): 426 (33) (M+), 425, 155, 135, 106
IR, ν˜/cm−1: 3300 (NH), 1646, 1638 (C O), 1610 (C C)
1H NMR (DMSO-d6), δ: 2.30 (s, 6H, 2CH3), 6.56 (s, 1H, H-4ꢀ), 7.58 (m, 3H, Ar-H, H-4), 7.88 (s, 1H, H-6), 8.36 (br
—
—
—
—
s, 1H, NH, D2O exchangeable)
MS, m/z (Ir/%): 307 (100) (M+
)
IR, ν˜/cm−1: 3437 (NH), 1667, 1641 (C O)
—
—
1H NMR (DMSO-d6), δ: 2.20 (s, 6H, 2CH3), 7.52 (s, 1H, H-4ꢀ), 7.99 (m, 6H, Ar-H, H-8), 8.48 (s, 1H, H-6), 8.60 (s,
1H, H-4), 8.74–8.76 (d, 1H, J = 6.8 Hz, H-9), 9.12 (br s, 1H, NH, D2O exchangeable)
MS, m/z (Ir/%): 383 (6) (M+), 307, 279, 251, 226, 170
IR, ν˜/cm−1: 3443 (NH), 1646 (C O)
—
—
1H NMR (CDCl3), δ: 2.49 (s, 6H, 2CH3), 6.40 (s, 1H, H-4ꢀ), 7.61 (m, 5H, Ar-H, H-8), 7.78 (d, 1H, J = 7.3 Hz, H-9),
8.02 (s, 1H, H-6), 8.34 (s, 1H, H-4), 8.81 (br s, 1H, NH, D2O exchangeable)
MS, m/z (Ir/%): 440 (100) (M+), 425, 424, 423, 307
3-(3-Methylpyrazol-5-yl)-5-oxo-5H-
[1]benzopyrano[3,2-e]pyridin-2-one (IXa)
3-(3-Methyl-1-benzothiazolylpyrazol-5-yl)-5-
oxo-5H-[1benzopyrano[3,2-e]pyridin-2-one
(IXc)
Va (3.36 mmol) was dissolved in ethanol (5–10 mL)
and hydrazine hydrate (3.36 mmol) was added. The
reaction mixture was heated under reflux for 3 h and
allowed to cool to room temperature to afford a light
yellow solid. It was filtered, washed with ethanol, dried
and re-crystallised from a chloroform-methanol mix-
ture. The yield was 0.69 g (2.35 mmol).
Va (3.36 mmol) was dissolved in ethanol (50 mL)
and 2-hydrazinobenzothiazole (3.36 mmol) was added.
The reaction mixture was heated under reflux for 5 h.
On cooling, a dirty-green solid was obtained, filtered,
washed with ethanol, dried and re-crystallised from
chloroform. The yield was 0.91 g (2.13 mmol).
3-(3-Methyl-1-phenylpyrazol-5-yl)-5-oxo-5H-
[1]benzopyrano[3,2-e]pyridin-2-one (IXb)
7-Methyl-3-(3-methylpyrazol-5-yl)-5-oxo-5H-
[1]benzopyrano[3,2-e]pyridin-2-one (IXd)
The equimolar amount of Va (3.36 mmol) and
phenylhydrazine (3.36 mmol) in ethanol (15 mL) was
heated under reflux for 2 h. The reaction mixture was
allowed to stand at room temperature as IXb crys-
tallised to form yellow crystals. The crystals were fil-
tered, washed with ethanol and dried. The yield was
0.74 g (2.00 mmol).
IXd compound was synthesised under similar re-
action conditions as IXa using Vb (3.21 mmol) and
hydrazine hydrate (3.21 mmol). The yield was 0.64 g
(2.08 mmol).

Z. N. Siddiqui et al./Chemical Papers 64 (6) 818–824 (2010)
821
OH O
O
O
O
O HO
O
II
I
NH2
O
NH2O
OH
O
O
O
O
CH3
O
O
CH3
Pyridine/ piperidine
RT/ 7
O
days
7 days
R
R
C
H
H
O
O
H
IIIa−b
IIIa, IIIb
IV
H
N
O
O
O
O
O
O
NH2O
O
O
CH3
Rearrangement
− H2O
CH3
R
R
R
O
O
H
10
O
9
N1
O
O
Ha
H
8
a, R = H
b, R = CH3
2
CH3
3
7
5
6
H
4
Hb
O
Va, Vb
Va−b
Fig. 1. Formation of 3-acetoacetyl benzopyranopyridones (Va and Vb).
7-Methyl-3-(3-methyl-1-phenylpyrazol-5-yl)-5-
oxo-5H-[1]benzopyrano[3,2-e]pyridin-2-one
(IXe)
of inhibition around the disc of the tested compound.
Chloramphenicol (30 µg per disc), an antibiotic, was
used as a positive control.
IXe was synthesised under similar reaction con-
ditions as IXb using Vb (3.21 mmol) and phenyl
hydrazine (3.21 mmol). The yield was 0.87 g (2.26
mmol).
Results and discussion
Salicylaldehyde reacts with 4-hydroxycoumarin to
give a product to which earlier workers assigned the
structure I (Sullvian et al., 1943). In a later study, I
was found to be untenable and it was revised to the
structure II (de March et al., 1984). Thus, in a se-
ries of papers, Spanish researchers showed that struc-
tures of type I are unstable and they consistently rear-
range to the type of structure II through intramolec-
ular translactonisation (Cervello et al., 1987) (Fig. 1).
Similarly, when salicylaldehyde was treated with
TAL, the rearranged product was obtained. Also, on
the basis of the above findings, as the amino group
is a stronger nucleophile than the hydroxyl group, an
intramolecular translactonisation was anticipated to
take place using 2-amino-3-formyl chromone III. As
—NH2 and —CHO groups are present in adjacent car-
bon atoms similar to salicylaldehyde, this reaction will
lead to rearranged products.
As predicted, the reaction took place with triacetic
acid lactone IV and afforded rearranged products Va
and Vb (Fig. 1). Va and Vb gave a positive ferric chlo-
ride test due to the presence of acetoacetyl unit. Thus,
these results supported the assumption that the rear-
rangement proceeded.
The IR spectrum of Vb exhibited absorption
bands at 1668 cm−1, 1649 cm−1, and 1618 cm−1 for
chromone, lactam, and chelated carbonyl groups, re-
7-Methyl-3-(3-methyl-1-benzothiazolylpyrazol-
5-yl)-5-oxo-5H-[sl1]benzopyrano[3,2-e]pyridin-
2-one (IXf )
IXf was synthesised under similar reaction condi-
tions as IXc usingVb (3.21 mmol) and hydrazinoben-
zothiazole (3.21 mmol). The yield was 0.98 g.(2.22
mmol).
Antibacterial activity
The microbial cultures were diluted in a nutrient
broth to obtain a cell suspension of 105 CFU mL−1
.
All the newly synthesised compounds were screen-
ed for antibacterial activity against gram-positive
and gram-negative bacteria by disc diffusion method
(Bauer et al., 1966) with a minor modification (Aqil
& Ahmad, 2003). Briefly, 0.1 mL of diluted inoculum
(105 CFU mL−1) of test bacteria was spread on nu-
trient agar plates. A sterile paper disc was impreg-
nated with 70 µg of compound dissolved in DMSO. A
disc without compound was used as a negative control.
Plates were incubated at 37◦C for 18 h. The antibac-
terial activity was evaluated by measuring the zone

822
Z. N. Siddiqui et al./Chemical Papers 64 (6) 818–824 (2010)
O
O
O
O
NH2O
OH
O
O
NH2
O
O
Methanol/pyridine
Reflux
O
C
H
O
H
H
IIIa
IIIb
VI
− H2O
a
route a
1
4
11
8
O
N
O
O
NH2O
O
2
3
10
Cyclization involving C-2 carbon
− H2O
9
5
7
O
6
b
O
O
O
VIIIa
Cyclization
involving C-4
carbon, − H2O
route b
11
12
10
9
H
1
O
O
N
HO
O
O
N
O
2
3
O
5
7
6
4
O
O
VII
VIIIb
Fig. 2. Pentacyclic benzopyranopyridines (VIIIa and VIIIb).
10
O
H
H
9
6
N1
O
O
O
N
O
O
8
R'NHNH2
2
4'
CH3
5'
CH3
3'
Ethanol/Reflux
3
R
R
7
5
4
O
O
N
N
R'
1'
2'
IXa−b
IXa–IXf
Va−b
Va, Vb
a, R = R' = H
a, R = H
b, R = CH3
b, R = H, R' = Ph
c, R = H, R' =
N
S
d, R = CH3, R, = H
e, R = CH3, R' = Ph
f, R = CH3, R' =
N
S
Fig. 3. Synthesis of pyrazoles IXa–IXf.
spectively. 1H NMR spectrum of Vb, exhibited two
upfield singlets at δ 2.24 and 2.49 due to the presence
of two methyl groups in the molecule. Three more sin-
glets at δ 6.40, 8.08, and 9.04 were assigned to Ha, H-
6, and Hb protons, respectively. The mass spectrum
exhibited a M+ base peak at m/z = 311 which fur-
ther confirmed the structure of the compound to be
Vb. However, a reaction with 4-hydroxycoumarin VI,
did not yield the expected rearranged product VII. In-
stead, isomeric compounds VIIIa and VIIIb were ob-
tained (Fig. 2). The formation of isomeric benzopyra-
nopyridines was similar to the reaction of phenol with
β-ketoester to afford a mixture of isomeric coumarin
and chromone (Ellis, 1977) through Simonis conden-
sation (Sethna & Shah, 1945). The two isomeric com-
pounds showing M+ at m/z = 315 were identified by
means of their IR and 1H NMR spectra. Thus, the
IR spectrum of VIIIa exhibited the presence of two
chromone carbonyl groups at 1670 cm−1 and 1665
cm−1 whereas the coumarin and chromone carbonyl
groups in VIIIb appeared at 1751 cm−1 and 1671
cm−1, respectively. The 1H NMR of VIIIa showed two
ortho-coupled doublets (J = 7.8 Hz, 7.5 Hz) for C-4
and C-8 protons of chromone moieties at δ 8.32 and
8.61, respectively. The most deshielded proton H-6 ap-
1
peared as a singlet at δ 9.59. The H NMR of VIIIb
showed one doublet at δ 8.37 corresponding to the
ortho-coupled (H-4) proton, and a singlet at δ 9.71 for
H-6 proton.
Pyrazoles are most conveniently synthesised from
1,3-dicarbonyl compounds and hydrazines (Katritzky
& Rees, 1984). Due to the presence of an acetoacetyl
unit in Va and Vb, pyrazoles IXa–IXf were obtained
easily in sufficient quantity on treatment with various
substituted hydrazines (Fig. 3). The IR spectra of IXa
displayed sharp bands at 1664 cm−1 and 1620 cm−1

Z. N. Siddiqui et al./Chemical Papers 64 (6) 818–824 (2010)
823
Table 3. Antibacterial activity of new compounds; concentration of 70 µg per disc of the compound tested was used
Inhibition zone diameter of compounds tested/mm
Test microrganism
Vb
VIIIa
VIIIb
IXa
IXb
IXc
IXd
IXe
IXf
Controla
S. aureus
S. pneumoniae
E. coli
P. aeuruginosa
S. typhi
S. dysenteriae
K. pneumoniae
8
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
13
–
–
12
–
8
10
–
7
–
–
–
–
–
–
–
–
–
–
–
–
–
–
12
–
–
11
–
12
13
22
21
23
–
16
23
23
–
12
19
18
15
a) Antibiotic control: chloramphenicol (30 µg per disc).
1
for chromone and pyridone carbonyl groups. The H
NMR exhibited singlets at δ 2.27 and 6.71 for methyl
and C-4ꢀ protons 9whereas a broad singlet integrating
for two protons at δ 8.69 was assigned to two NH
protons. The C-6 proton of chromone unit appeared
as a split doublet at δ 8.17 (J = 7.8 Hz, 3 Hz). This
structure was further confirmed in the mass spectrum,
which showed M+ at m/z = 293.
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Faruk, E. A., Hamilton, T. C., Nash, D. J., Stemp, G., &
Willcocks, K. (1986). Synthesis and antihypertensive activity
of 4-(cyclic amido)-2H-1-benzopyrans. Journal of Medicinal
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Ashwood, V. A., Cassidy, F., Evans, J. M., Gagliardi, S., &
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The compounds exhibited antibacterial activity
against both Gram-positive and Gram- negative bac-
teria except for VIIIa, VIIIb, IXa, IXd, and IXe which
were inactive. Compound Vb was active against gram-
positive bacteria (Staphylococcus aureus) only. The
remaining compounds IXb, IXc, and IXf were active
against both gram-positive and gram-negative bacte-
ria. Out of the gram-negative bacteria tested, Kleb-
siella pneumoniae and Shigella dysenteriae were more
sensitive, Salmonella typhi showed a medium activity,
and Escherichia coli exhibited a negligible sensitivity
to IXc. Of the gram-positive bacteria, only S. aureus
exhibited minor sensitivity to IXc. Compounds IXb
and IXf exhibited medium activity against only one
strain of S. aureus (gram-positive bacteria) whereas,
of the gram-negative bacteria tested, Pseudomonas
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ramphenicol (control). These two compounds exhib-
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activity against S. dysenteriae, whereas IXf showed
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Acknowledgements. Financial assistance in the form of a
major research project from the University Grants Commis-
sion, New Delhi, is gratefully acknowledged. The authors would
also like to thank Dr. Indu Shukla, Chair of the Department
of Microbiology, Jawahar Lal Nehru Medical College, Aligarh
Muslim University, Aligarh, India for biological screening. The
authors are grateful to SAIF, CDRI, Lucknow, India for pro-
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