Synthesis, antioxidant and antimicrobial activity of novel benzene-1,4-diamine-bis-dioxaphosphepine-6λ5 iminophosphoranes

Article abstract of DOI:10.1002/jhet.358

(Chemical Equation Presented). A new class of novel benzene-1,4-diamine- bis-dioxaphosphepine-6λ⁵ iminophosphoranes (5a-j) were synthesized by the reaction of 6-chlorodibenzo[d,f][1,3,2]dioxaphosphepine (2) with 1,4-diaminobenzene to form bis-dibenzo[d,f][1,3,2]dioxaphosphepin-6-yl- benzene-diamine (3). Its subsequent reaction with different alkyl/aryl azides (4a-j) in tetrahydrofuran at 50-60°C under inert atmosphere yielded title compounds. Their structures were established by elemental analysis, IR, ¹H, ¹³C, ³¹P NMR, and mass spectral studies. All the title compounds were screened for antioxidant properties and found to exhibit potent in vitro antioxidant and antimicrobial activity.

Full text of DOI:10.1002/jhet.358

538
Synthesis, Antioxidant and Antimicrobial Activity of Novel
Benzene-1,4-diamine-bis-dioxaphosphepine-6k5
Iminophosphoranes
Vol 47
M. Veera Narayana Reddy, G. Chandra Sekhar Reddy, K. Suresh Kumar,
C. Suresh Reddy,* and C. Naga Raju
Department of Chemistry, Sri Venkateswara University, Tirupati-517 502, Andhra Pradesh, India
*E-mail: csrsvu@gmail.com
Received August 31, 2009
DOI 10.1002/jhet.358
Published online 2 April 2010 in Wiley InterScience (www.interscience.wiley.com).
A new class of novel benzene-1,4-diamine-bis-dioxaphosphepine-6k5 iminophosphoranes (5a–j) were
synthesized by the reaction of 6-chlorodibenzo[d,f][1,3,2]dioxaphosphepine (2) with 1,4-diaminobenzene
to form bis-dibenzo[d,f][1,3,2]dioxaphosphepin-6-yl-benzene-diamine (3). Its subsequent reaction with
different alkyl/aryl azides (4a–j) in tetrahydrofuran at 50–60ꢀC under inert atmosphere yielded title
compounds. Their structures were established by elemental analysis, IR, 1H, 13C, 31P NMR, and mass
spectral studies. All the title compounds were screened for antioxidant properties and found to exhibit
potent in vitro antioxidant and antimicrobial activity
J. Heterocyclic Chem., 47, 538 (2010).
INTRODUCTION
phils, and chondrocytes [5]. The inflammed rheumatoid
joint also undergoes a hypoxia–reperfusion cycle, which
results in ROS generation [6]. Antioxidants may have a
therapeutic role in RA by suppressing the inflammation.
As our synthesized compounds are contrast in the struc-
ture to bisphosphonates, the aim of this study was to
investigate the in vitro antioxidant profile of different
bis-iminophosphoranes. To the best of our knowledge
the antioxidant profile of different bis-iminophosphranes
has not yet been systematically studied.
In recent years, the detailed mechanism of antioxidant
action of organophosphorus compounds and their rela-
tionships between chemical structure and antioxidant ac-
tivity have been comprehensively studied, in spite of
their great practical importance. Depending on their
structure and scavenging activity, phosphites and phos-
phonates may act as both primary and secondary antiox-
idants [1,2]. Reactive oxygen species (ROS) are pro-
duced by univalent reduction of dioxygen to superoxide
anion which in turn disproportionate to H2O2 and O2
spontaneously. The ROS are believed to play a major
role in the inflammatory process in rheumatoid arthritis
(RA) and contribute to the destruction of cartilage and
bone [3,4]. The most important ROS implicated in
inflammatory tissue injury are superoxide radical (Oꢁ2ꢂ),
hydrogen peroxide (H2O2), hydroxyl radical (HOꢁ), and
hypochlorous acid (HOClꢁ). In the inflammed joint,
these ROS can be produced by macrophages, neutro-
RESULTS AND DISCUSSION
Cyclization of 2,20-dihyroxybiphenyl (1) with phos-
phorus trichloride at 0ꢀC under dry and inert conditions
in the presence of triethylamine (TEA) in tetrahydrofu-
ran (THF) afforded the corresponding 6-chlorodiben-
zo[d,f][1,3,2]dioxaphosphepine (2). Reaction of 2 with
1,4-diaminobenzene led to bis dibenzo[d,f][1,3,2]dioxa-
phosphepin-6-yl]-1,4-benzenediamine (3). Further reac-
C
V
2010 HeteroCorporation

May 2010
Synthesis, Antioxidant and Antimicrobial Activity of Novel
Benzene-1,4-diamine-bis-dioxaphosphepine-6k5 Iminophosphoranes
539
Scheme 1
were performed at the Central Drug Research Institute, Luck-
now, India. Infrared spectra (mmax in cmꢂ1) were recorded as
KBr pellets on a Perkin-Elmer 283 double beam spectropho-
tometer. 1H, 13C, and 31P NMR spectra were recorded on
AMX 400 MHz spectrophotometer operating at 400 MHz for
1H NMR, 100 MHz for 13C NMR, and 161.9 MHz for 31P
NMR, using DMSO-d6 as solvent. The 1H and 13C NMR
chemical shifts were referenced to Tetra Methyl Silane (TMS)
and 31P NMR chemical shifts to 85% H3PO4.
tion of 3 with different organic azides 4a–j in dry THF
at 50–60ꢀC led to 5a–j in high yields (Scheme 1). The
reactions were monitored by thin layer chromatography
(TLC). The chemical structures of 5a–j were confirmed
1
by elemental analysis and spectral data (IR, H, 13C, 31P
NMR, and mass spectra).
Characteristic IR absorptions were observed for CAN,
P¼¼N, and NH in the regions 1010–1081, 1206–1265,
and 3280–3410 cmꢂ1, respectively [7]. The aromatic
hydrogens resonated as multiplets at d 6.45–7.99, the
PANH proton chemical shift appeared as a singlet at d
3.75–5.20. The chemical shifts of other aliphatic hydro-
gens and carbon-13 5a–j appeared in the expected
region [8]. 31P NMR chemical shifts were observed in
the region d 4.25–9.20 [7]. LCMS of 5a, 5b, 5e, 5g, 5i,
and 5j gave molecular ion peaks and diagnostic daugh-
ter ions at their expected m/z values.
Typical experimental procedure.
Preparation of alkyl azides. In a dry 100-mL round-bot-
tomed flask fitted with dropping funnel, calcium chloride guard
tube, sodium azide (0.64 g, 0.01 mole), and 10 mL of dry
THF were placed and stirred. Alkyl/aryl bromide (0.01 mole)
in 10 mL of dry THF was added to it at room temperature.
Temperature of the reaction mixture was raised to 40–45ꢀC
and stirred for 4 h. After cooling to room temperature, it was
filtered to remove sodium bromide. The filtrate containing
alkyl/aryl azide was used for the next step reaction.
N1,N4 Bis[6-(alkyl/arylimino)-6ꢀ5-dibenzo[d,f][1,3,2]dioxa-
phosphepine-6yl]benzene-1,4-diamine 5a–j. A solution of
slight excess of phosphorus trichloride (0.43 g, 0.005 mole) in
dry THF (25 mL) under nitrogen atmosphere, was added drop-
wise to a well-stirred solution of 2,20-dihydroxybiphenyl(1)
(0.930 g, 0.005 mole) and TEA (1.4 g, 0.01 mole) in dry
THF(20 mL) at 0ꢀC. After the addition, the temperature of the
reaction mixture was slowly raised and kept at 25–30ꢀC for
1 h. The reaction progress was monitored by TLC. The mix-
ture was filtered to remove triethylamine hydrochloride and
the filtrate was rota-evaporated. The residue-6-chlorodiben-
zo[d,f][1,3,2]dioxaphosphepine (2) was used for the next
step.
The radical scavenging capacity of 5a–j was evaluated
by using methods such as 1,1-diphenyl-2-picryl hydrazyl
(DPPH) and nitric oxide scavenging activity. 5j showed
appreciable antioxidant activity. Because of ANO2 sub-
stituents which affect the electron and hydrogen donating
capacities, appears to be useful in inducing antioxidant ac-
tivity. As ANO2 is highly withdrawing moiety, thereby
electron density around phosphonate moiety decrease and
increases affinity toward oxygen derived free radicals and
mobilizes ROS to be scavenged out of living system.
EXPERIMENTAL
To the intermediate 2 in dry THF (20 mL), 1,4-diaminoben-
zene (0.548 g, 0.05 mole) was added at 10ꢀC in the presence
of TEA at nitrogen atmosphere in dry THF. After the addition,
All melting points were determined in open capillary tubes
on Mel-Temp apparatus and are uncorrected. Microanalyses
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

540
M. V. Narayana Reddy, G. C. Sekhar Reddy, K. S. Kumar, C. S. Reddy, and C. N. Raju
Vol 47
the reaction mixture was brought to 30–40ꢀC and stirred for
2 h to complete the reaction. It was treated with alkyl/aryl
azides (0.01 mole) in THF at 50–60ꢀC and stirred for 4 h to
complete the reaction. The progress of the reaction was moni-
tored by TLC (ethyl acetate:hexane, 2:8) analysis. After com-
pletion of the reaction, solvent was removed in a rota-evapora-
tor to get crude products. The residue was purified by column
chromatography on silicagel (80–120 mesh) using petroleum
ether-ethylacetate (8:2) as eluant. It was recrystallized from 2-
propanol to afford pure (5a–j).
Table 1
DPPH radical scavenging activity of 5a–j.
Compound
IC50 (lg/mL)
5a
5b
5c
5d
5e
5f
5g
5h
5i
19
19
14
13
25
.13
16
N1,N4-Bis[6-(methylimino)-6ꢀ5-dibenzo[d,f][1,3,2]dioxaphos-
phepin-6-yl]-1,4-benzene-diamine (5a). Yield 65%, viscous liq-
uid; 1H NMR (DMSO-d6): d 6.81–7.96 (20H, m, Ar-H), 3.78
(2H, s, NH), 0.88 (6H, s, CH3); 13C NMR data: 131.01 (C-1,
C-11), 117.61 (C-2, C-10), 127.5 (C-3, C-9), 112.5 (C-4, C-8),
120.0 (C-12, C-13), 151.6 (C-14, C-15), 132.0 (C0-1, C0-4),
114.5 (C0-2, C0-3, C0-5, C0-6), 21.4 (CH3-N); 31P NMR data: d
6.75; IR (KBr) cmꢂ1: 3385 (PANH), 1208 (PAN), 1045
15
13
5j
BHT
11
72.50
4.35 (2H, s, NH), 2.81–2.98 (2H, m, CH), 1.16 (12H, d, J
¼10.2Hz, CHACH3); 13C NMR data: 131.2 (C-1, C-11), 116.3
(C-2, C-10), 130.3 (C-3, C-9), 113.0 (C-4, C-8), 126.3 (C-12,
C-13), 154.0 (C-14, C-15), 132.0 (C0-1, C0-4), 115.6 (C0-2, C0-
3, C0-5, C0-6), 30.6 (CH-N),16.6 (CH3); 31P NMR data: d 4.25;
IR (KBr) cmꢂ1: 3370 (PANH), 1216 (P¼¼N), 1043 (NAC);
Anal. Calcd for C36H36N4O4P2: C,66.46; H, 5.58; N, 8.61.
Found C, 66.40; H, 5.51; N, 8.56.
N1,N4-Bis[6-(isobutylimino)-6ꢀ5-dibenzo[d,f][1,3,2]dioxaphos-
phepin-6-yl]-1,4-benzene-diamine (5g). Yield 72%, viscous liq-
uid; H NMR (DMSO-d6): d 6.79–7.81 (20H, m, Ar-H), 4.18
(2H, s, NH), 1.52–1.91 (2H, m, CHACH2), 1.28 (4H, d, J ¼
5.4 Hz, CH2ACH), 1.15 (12H, t, J ¼ 10.2 Hz, CHACH3);
13C NMR data: 131.6 (C-1, C-11), 118.7 (C-2, C-10), 128.4
(C-3, C-9), 114.8 (C-4, C-8), 125.7 (C-12, C-13), 155.0 (C-
14, C-15), 127.4 (C0-1, C0-4), 117.3 (C0-2, C0-3, C0-5, C0-6),
35.0 (CH), 29.0 (NACH2), 19.2 (CHACH3); 31P NMR data:
d 9.20; IR (KBr) cmꢂ1: 3357 (PANH), 1206 (P¼¼N), 1058
(NAC); LCMS m/z: 678 (Mþ); Anal. Calcd. for
C38H40N4O4P2: C,67.25; H, 5.94; N, 8.26. Found C, 67.19;
H, 5.90; N, 8.21.
(NAC); LCMS m/z: 595 (Mþ
C32H28N4O4P2: C, 64.65; H, 4.75; N, 9.42. Found C, 64.60; H,
4.68; N, 9.36.
þ
1); Anal. Calcd. for
N1,N4-Bis[6-(ethylimino)-6ꢀ5-dibenzo[d,f][1,3,2]dioxaphos-
phepin-6-yl]-1,4-benzene-diamine (5b). Yield 68%, viscous
liquid; 1H NMR (DMSO-d6): d 6.88–7.90 (20H, m, Ar-H),
3.95 (2H, s, NH), 1.88–2.01 (4H, m, CH2), 1.22 (6 H, t, J ¼
11.5 Hz, -CH3); 31P NMR data: d 7.78; IR (KBr) cmꢂ1: 3280
(PANH), 1225 (P¼¼N), 1055 (NAC); LCMS m/z: 626 (Mþ
þ
1
1); Anal. Calcd. for C34H32N4O4P2: C, 65.59; H, 5.18; N,
9.00. Found C, 65.51; H, 5.09; N, 8.95.
N1,N4-Bis[6-(propylimino)-6ꢀ5-dibenzo[d,f][1,3,2]dioxaphos-
phepin-6-yl]-1,4-benzene-diamine (5c). 65%, viscous liquid; H
1
NMR (DMSO-d6): d 6.76–7.70 (20H, m, Ar-H), 4.51(2H, s,
NH), 1.60 (4H, t, J ¼ 9.5 Hz, ACH2ACH2ACH3), 1.33–1.34
(4H, m, CH2ACH2ACH3), 0.98 (6H, t,
J
¼
10.3 Hz,
ACH2ACH2ACH3); 31P NMR data: d 5.25; IR (KBr) cm1:
3350 (PANH), 1220 (P¼¼N), 1010 (NAC); Anal. Calcd. for
C36H36N4O4P2: C, 66.46; H, 5.58; N, 8.61. Found C, 66.40; H,
5.51; N, 8.55.
N1,N4-Bis[6-(butylimino)-6ꢀ5-dibenzo[d,f][1,3,2]dioxaphos-
phepin-6-yl]-1,4-benzene-diamine (5d). Yield 69%, viscous
liquid; 1H NMR (DMSO-d6): d 6.80–7.82 (20H, m, Ar-H),
5.25 (2H, s, NH), 1.51 (4H, t, J ¼ 6.8 Hz, ACH2ACH2ACH3),
1.23–1.40 (8H, m, CH2ACH2ACH2ACH3), 0.95 (6H, t, J ¼
10.9 Hz, ACH2ACH2ACH2ACH3); 31P NMR data: d 8.10; IR
(KBr) cmꢂ1: 3410 (PANH), 1265 (P¼¼N), 1025 (NAC); Anal.
Calcd. for C38H40N4O4P2: C, 67.25; H, 5.94; N, 8.26. Found
C, 67.20; H, 5.86; N, 8.18.
N1,N4-Bis[6-(allylimino)-6ꢀ5-dibenzo[d,f][1,3,2]dioxaphosphe-
pin-6-yl]-1,4-benzene-diamine(5h). Yield 71%, viscous liquid;
1H NMR (DMSO-d6): d 6.80–7.99 (20H, m, Ar-H), 5.71 (2H,
m, CH), 5.02–5.10 (4H,m, CH2),4.10 (2H, s, NH) 2.10 (4H, d,
J ¼ 5.2Hz, NACH2); 31P NMR data: d 9.10; IR (KBr) cmꢂ1
:
3290 (PANH), 1210 (P¼¼N), 1029 (NAC); Anal. Calcd. for
C36H32N4O4P2: C, 66.87; H, 4.99; N, 8.66. Found C, 66.80; H,
4.92; N, 8.60.
N1,N4-Bis[6-(benzylimino)-6ꢀ5-dibenzo[d,f][1,3,2]dioxaphos-
phepin-6-yl]-1,4-benzene-diamine (5i). Yield 75%, viscous liq-
N1, N4-Bis[6-(vinylimino)-6ꢀ5-dibenzo[d,f][1,3,2]dioxaphos-
phepin-6-yl]-1,4-benzene- diamine (5e). Yield 73%, viscous liq-
uid; 1H NMR (DMSO-d6): d 6.45–7.52 (20H, m, Ar-H), 5.05
(2H, t, J ¼ 11 Hz, CH¼¼CH2), 4.22 (4H, d, J ¼ 5.3 Hz,
CH2¼¼CH), 3.82 (2H, s, NH); 13C NMR data: 128.0 (C-1, C-11),
118.7 (C-2, C-10), 127.4 (C-3, C-9), 113.1 (C-4, C-8), 125.7 (C-
12, C-13), 151.0 (C-14, C-15), 145.0 (N-CH), 117.4 (CH¼¼CH2),
132.2 (C0-1, C0-4), 114.8 (C0-2, 3,5); 31P NMR data: d 6.59; IR
(KBr) cm1: 3392 (PANH), 1209 (P¼¼N), 1081 (NAC); LCMS
m/z: 618 (Mþ); Anal. Calcd for C34H28N4O4P2: C, 66.02; H,
4.56; N, 9.06. Found C, 65.96; H, 4.51; N, 9.01.
1
uid; H NMR (DMSO-d6): d 6.80–7.96 (30H, Ar-H), 3.75 (2H,
s, NH), 2.01 (4H, s, CH2-Ar); 13C NMR data: 128.4 (C-1, C-
11), 118.7 (C-2, C-10), 127.4 (C-3, C-9), 114.8 (C-4, C-8),
125.7 (C-12, C-13), 155.0 (C-14, C-15), 136.2 (C0-1, C0-4),
117.3 (C0-2, C0-3, C0-5, C0-6), 140.1 (C00-1), 130.1 (C00-2, C00-
6), 128.2 (C00-3, C00-5), 125.8 (C00-4), 28.09 (CH2-Ar); 31P
NMR data: d 4.94; IR (KBr) cmꢂ1: 3390 (PANH), 1244.9
(P¼¼N), 1045 (NAC); LCMS m/z: 746 (Mþ); Anal. Calcd for
C44H36N4O4P2: C, 70.77; H, 4.86; N, 7.50. Found C, 70.71; H,
4.81; N, 7.45.
N1,N4-Bis[6-(isopropylimino)-6ꢀ5-dibenzo[d,f][1,3,2]dioxa-
phosphepin-6-yl]-1,4-benzene-diamine (5f). Yield 70%, vis-
N1,N4-Bis[6-(nitrobenzylimino)-6ꢀ5-dibenzo[d,f][1,3,2]diox-
aphosphepin-6-yl]-1,4-benzene-diamine (5j). Yield 71%, vis-
cous liquid; 1H NMR (DMSO-d6): d 6.80–7.92 (28H, m,
1
cous liquid; H NMR (DMSO-d6): d 6.91–7.79 (20H, m,Ar-H),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2010
Synthesis, Antioxidant and Antimicrobial Activity of Novel
Benzene-1,4-diamine-bis-dioxaphosphepine-6k5 Iminophosphoranes
541
Table 2
Table 4
Antifungal activitya of 5a–j.
Nitric oxide scavenging activity of 5a–j.
Name of the compound
IC50 (lg/mL)
Zone of inhibition/mm
Helminthosporium
oryzae
5a
5b
5c
5d
5e
5f
5g
5h
5i
20
22
Aspergillus niger
100 50 25
35
29
100
50
25
Compd.
(ppma) (ppma) (ppma) (ppma) (ppma) (ppma)
55
24
25
22
26
14
357.14
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
9
10
12
11
10
11
8
7
8
5
4
6
8
5
3
4
6
9
6
5
11
11
12
14
12
12
9
6
9
5
5
7
4
7
9
4
5
8
4
5
9
10
10
8
10
7
5j
BHT
5
6
10
8
9
12
8
8
11
9
11
13
9
9
12
7
Ar-H), 4.20 (2H, s, NH), 2.15 (4H, s, Ar-CH2); 31P NMR data:
d 5.25; IR (KBr) cmꢂ1: 3390 (PANH), 1225 (P¼¼N), 1020
(NAC); LCMS m/z: 808 (Mþ þ1); Anal. Calcd. for
C44H34N6O8P2: C, 63.16; H, 4.10; N, 10.04. Found C, 63.11;
H, 4.05; N, 9.99.
bGriseofulvn
12
10
12
10
a In DMF.
b Reference compound.
ANTIOXIDANT ACTIVITY
The antioxidant activity of these compounds was
expressed as IC50 (Inhibition concentration, 50%) of 5j
which showed highest DPPH scavenging activity with
11 lg/mL when compared with other compounds (Table
1). The percent of inhibition of free radical production
from DPPH was calculated by using the following equa-
tion. Butylated hydroxyl toluene (BHT) was used as a
standard reference compound.
DPPH radical scavenging activity. The hydrogen or
electron donation abilities of title compounds were
measured from the bleaching of the purple color metha-
nol solution of DPPH [9]. This spectrophotometric assay
uses the stable radical DPPH as a reagent. One milliter
of various concentrations of the title compounds (20, 40,
60, 80, and 100 lg/mL) in methanol were added to 4
mL of 0.004% methanol solution of DPPH. After a 30
min incubation period at room temperature, the absorb-
ance was red against blank at 517 nm.
½ðAcontrolÞ ꢂ ðAsampleÞꢃ
I ¼
100
(1)
Blank
where, Acontrol is absorbance of the control.
Table 3
Control reaction containing the entire reagent except
the test compound.
Antibacterial activity of 5a–j.
Asample is absorbance of the test compound.
Zone of inhibition/mm
Nitric oxide scavenging activity. Nitric oxide scav-
enging activity was measured by slightly modified meth-
ods of Green et al. and Marcocci et al. [10]. Nitric ox-
ide radicals were generated from sodiumnitropruside.
One milliliter of sodiumnitroprusside (mM) and 1.5 mL
of phosphate buffer saline (0.2M, pH 7.4) were added to
the different concentrations (20, 40, 60, 80, and 100 lg)
of the extract and incubated for 150 min at 25ꢀC. After
incubation, 1 mL of the reaction mixture was treated
with 1 mL of Griess reagent (1% Sulfanilamide, 2% of
H3PO4 and 0.1% naphthylethylene diamine dihydro
chloride).
Staphylococcus aureus
Escherichia coli
100
50
25
100
50
25
Compd. (ppma) (ppma) (ppma) (ppma) (ppma) (ppma)
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
11
8
10
6
8
6
8
6
–
6
4
5
8
–
5
8
5
–
12
10
12
12
14
13
9
8
7
8
4
5
4
6
8
7
4
5
4
6
–
5
6
14
13
7
10
12
11
9
9
11
4
12
11
8
8
10
10
12
12
6
10
8
6
8
bPenicillin
6
8
Absorbance was measured at 546 nm. 5j showed
highest DPPH scavenging activity with 14 mg/mL when
compared with other compounds (Table 2). Butylated
a In DMF
b Reference compound.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

542
M. V. Narayana Reddy, G. C. Sekhar Reddy, K. S. Kumar, C. S. Reddy, and C. N. Raju
Vol 47
Acknowledgment. The authors thank Prof. C.D. Reddy,
Department of Chemistry, S.V. University, Tirupati for
helpful discussions and for UGC (33-299) New Delhi for
providing financial assistance. The authors also express
their thanks to Prof. Ch. Appa Rao and S. Swapna, Depart-
ment of Biochemistry, S.V. University, Tirupati for con-
ducting antioxidant and antimicrobial activity.
hydroxy toluene was added as a standard. The percent
of inhibition (I %) was calculated by using the following
equation:
½ðAcontrolÞ ꢂ ðAsampleÞꢃ
I ¼
100
(2)
Blank
Antibacterial activity. Antibacterial activity of all
the title compounds (5a–j) was assayed [11] against
Staphylococcus aureus ATCC-25923 (Gram positive)
and Escherichia coli ATCC-25922 (Gram-negative) at
three different concentrations (100, 50, and 25 ppm) in
DMF (Table 3). The compounds were diluted in DMF
for bioassay. Solvent control was included although no
antibacterial activity has been noted in the solvent
employed. Penicillin G (Hi-media) controls (20 lg/mL1)
were included to compare with compounds (5a–j). All
samples were tested in triplicate and average results
were recorded.
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Antifungal activity. The compounds (5a–j) were
screened for their antifungal activity (Table 4) against
Aspergillus niger and Helminthosporium oryzae species
along with standard fungicide Griseofulvin at three dif-
ferent concentrations (100, 50, and 25 ppm) in DMF
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high antifungal activity when compared with that of the
reference compound. The majority of the compounds
exhibited high activity against fungi.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet