Microwave-assisted synthesis, molecular docking, and biological evaluation of 2-arylidene-2H-furo[2,3-f]chromen-3(7H)-ones as antioxidant and antimicrobial agents

Article abstract of DOI:10.1007/s00044-017-1834-9

An efficient microwave-assisted method of synthesis of some novel 2-arylidene-2H-furo[2,3-f]chromen-3(7H)-ones 6a–j in excellent yields was described and structural assignment of the products was confirmed on the basis of IR, ¹H NMR, ¹³

Full text of DOI:10.1007/s00044-017-1834-9

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res
DOI 10.1007/s00044-017-1834-9
ORIGINAL RESEARCH
Microwave-assisted synthesis, molecular docking, and biological
evaluation of 2-arylidene-2H-furo[2,3-f]chromen-3(7H)-ones as
antioxidant and antimicrobial agents
Dongamanti Ashok1 Kavitha Rangu1 Srinivas Gundu1 Arunapriya Lakkadi2
Parthasarathy Tigulla2
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Received: 25 July 2016 / Accepted: 1 March 2017
© Springer Science+Business Media New York 2017
Abstract An efficient microwave-assisted method of
synthesis of some novel 2-arylidene-2H-furo[2,3-f]chro-
men-3(7H)-ones 6a–j in excellent yields was described and
structural assignment of the products was confirmed on the
Introduction
Free radicals that are reactive oxygen species such as
hydroxyl radicals, superoxide radicals, singlet oxygen,
hydrogen peroxide radical are constantly formed as a result
of normal organ functions or excessive oxidative stress (Yin
et al. 2011). Cellular damage arising from these free radicals
is one of the fundamental mechanisms underlying a number
of human neurodegenerative disorders such as diabetes,
cancer, coronary heart diseases, inflammation, and aging
(Hangum-balkir and Mckenney 2012; Turkoglu et al. 2007).
Antioxidants, such as butylated hydroxytoluene (BHT) and
butylated hydroxyanisole, which are commercially avail-
able, are currently being used as radical scavengers. How-
ever, since suspected actions as promoters of carcinogenesis
and other side effects have been reported, their use in food,
cosmetic, and pharmaceutical products has been decreasing
(Politeo et al. 2007; Tepe et al. 2005; Ku and Mun 2008;
Gulcin et al. 2003). Thus, there has been an upsurge of
interest in discovery of new and more effective antioxidant
agents. On the other hand, infectious diseases caused by
microorganisms are one of the main threats to the popula-
tion of the world. There is an urgent need to search for new
antibacterial and antifungal drugs with broad spectrum of
activity because of the increasing resistance of microbial
pathogens. It is desirable to find drugs with improved
potency and wide activity spectrum.
1
basis of IR, H NMR, 13C NMR, MS, and analytical data.
The synthesized compounds were screened for antioxidant
activity using 2,2-diphenyl-1-picrylhydrazyl and hydrogen
peroxide radicals. The compounds 5d, 5h, 6a, 6e, and 6j
exhibited better radical scavenging ability. Antimicrobial
activity results demonstrated that compounds 5b, 5e, 6b, 6c,
and 6e showed promising antimicrobial potency. The
in silico molecular docking studies were also carried out for
the inhibition of cyclooxygenase-II enzyme. These mole-
cular docking results were well complemented to the anti-
oxidant activity studies.
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Keywords Chromenone Aurone Microwave irradiation
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Molecular docking Antioxidant Antimicrobial
Electronic supplementary material The online version of this article
(doi:10.1007/s00044-017-1834-9) contains supplementary material,
which is available to authorized users.
Aurones (2-benzylidenebenzofuran-3(2H)-ones) are a
class of flavonoids found in yellow pigments of plants (Pare
et al. 1991). Natural and synthetic aurones have been shown
to possess a broad spectrum of bioactivity including antic-
ancer (Sim et al. 2011; Cheng et al. 2010), antioxidant
(Detsi et al. 2009), antiparasitic (Roussaki et al. 2012;
Kerboeuf et al. 2008) antiviral, antiparasitic, antifungal,
antidiabetic (Boumendjel 2003), and neuroprotective
* Dongamanti Ashok
ashokdou@gmail.com
1
Green and Medicinal Chemistry Laboratory, Department of
Chemistry, Osmania University, Hyderabad 500007, India
2
Molecular Modeling Laboratory, Department of Chemistry,
Osmania University, Hyderabad 500007, India

Med Chem Res
(Shrestha et al. 2013). 2-Benzylidine-benzofuranone based
flavopiridol drug (A) is used as selective CDK1 inhibitor
(Schoepfer et al. 2002) and Sulfuretin (B) is a naturally
occuring aurone flavonoid known to possess diverse bio-
logical activities, such as anti-nociceptive (Kim et al. 2004),
antioxidant (Jung et al. 2003), anti-mutagenic (Park et al.
2004), and antidiabetic (Lee et al. 2008; Song et al. 2010)
(Fig. 1). 4′-Chloroaurone (C) is a naturally occuring aurone
known to possess antioxidant and antibacterial activity
(Venkateswarlu et al. 2007) (Fig. 1). In recent years
microwave-assisted organic synthesis has gained popularity
as an environmental benign technology. Microwave-
assisted synthesis leads to significantly reduced reaction
times, enhanced conversions and known to be environment
friendly (Ashok et al. 2016).
Keeping in view of the therapeutic importance of aurones
and furochromenone scaffolds, in order to investigate the
combined enhanced effect of these motifs on biological
potency, and in continuation of our search on biologically
potent molecules, we hereby report the synthesis, char-
acterization, and biological studies of some novel 2-
arylidene-2H-furo[2,3-f]chromen-3(7H)-ones under micro-
wave irradiation as well as conventional heating. The new
derivatives were screened for antioxidant and antimicrobial
activity. The molecular-docking studies of the compounds
for better understanding of the drug-receptor interaction
were also carried out.
Results and discussion
Chemistry
Traditionally, aurones have been prepared from 2-hydro-
xychalcones, which were synthesized from 2-
hydroxyacetophenones and aromatic benzaldehydes under
Claisen–Schmidt conditions, which could undergo oxida-
tive cyclization to furnish aurone ring system. The synthetic
route for the 2-arylidene-2H-furo[2,3-f]chromen-3(7H)-
ones is illustrated in Scheme 1 and Scheme 2. All these
syntheses involve the preliminary preparation of 1-(5-
hydroxy-2H-chromen-6-yl)ethanone (3) starting from resa-
cetophenone (1) upon treating with propargyl bromide in
presence of anhydrous K2CO3 in dry acetone yielded 1-(2-
hydroxy-4-(prop-2-yn-1-yloxy)phenyl)ethanone (2), was
further refluxed in N,N-dimethyl aniline at 180 °C for 3 h
gave compound (3) (Sreenivas 2011) (Scheme 1).
Claisen–Schmidt condensation between 1-(5-hydroxy-2H-
chromen-6-yl)ethanone (3) and substituted aromatic alde-
hydes (4a–j) in presence of powdered KOH under
Fig. 1 Biologically significant
aurone-based scaffolds
Scheme 1 Synthesis of 1-(5-
hydroxy-2H-chromen-6-yl)
ethanone (3)
Scheme 2 Synthesis of 2-
arylidene-2H-furo[2,3-f]
chromen-3(7H)-ones (6a–j)

Med Chem Res
Table 1 Physical data of
synthesized compounds 5a-j and
6a-j
Compound
Ar
Conventional heating
Microwave irradiation
Time (h)
Yield (%)
Time (min)
Yield (%)
5a
5b
5c
5d
5e
5f
phenyl
12
16
18
10
24
12
10
10
12
12
4
56
62
64
53
58
60
57
64
66
55
65
66
57
61
66
62
59
67
65
70
4
4
5
6
7
5
7
4
6
5
3
4
4
5
4
5
5
3
4
4
81
86
82
82
84
79
85
84
87
80
82
85
81
84
88
86
84
80
81
84
4-bromophenyl
2-chlorophenyl
4-isopropylphenyl
2,4-dichlorophenyl
4-methylphenyl
4-methoxyphenyl
3,4-dimethoxyphenyl
2-thiophenyl
5g
5h
5i
5j
3-indolyl
6a
6b
6c
6d
6e
6f
phenyl
4-bromophenyl
2-chlorophenyl
4-isopropylphenyl
2,4-dichlorophenyl
4-methylphenyl
4-methoxyphenyl
3,4-dimethoxyphenyl
2-thiophenyl
4
5
4.5
5
4
6g
6h
6i
4
4.5
4
6j
3-indolyl
5
microwave irradiation for 5–7 min (Scheme 2) gave (E)-3-
(aryl)-1-(5-hydroxy-2H-chromen-6-yl)prop-2-en-1-ones
(5a–j). These chalcones were then oxidatively cyclized
using mercury(II) acetate as the oxidative agent in pyridine
under microwave irradiation to furnish the aurone deriva-
tives 6a–j in excellent yields.
recorded and reported as [M + H]+ values, exhibited the
peak at m/z 310 for the compound 6c.
Biological evaluation
Antioxidant activity
Preliminarily, the synthesis of compounds 5a–j and 6a–j
was carried out under conventional heating method, but this
method suffers from poor yields (40–54%). In order to
improve the yields and reduce the reaction time, the
synthesis approach was changed to microwave irradiation
method. Microwave-assisted synthesis of title compounds
6a–j is advantageous over conventional method in terms of
higher yields in shorter reaction times. Comparison of
yields of title compounds in conventional and microwave
irradiation methods was demonstrated in Table 1. Forma-
tion of 2-arylidene-2H-furo[2,3-f]chromen-3(7H)-ones 6a–j
was confirmed by recording IR, 1H-NMR, 13C-NMR, mass
and elemental analyses. IR (Infra red) spectrum of com-
pound 6c showed absorption band at 1699 cm−1 due to α,β
The antioxidant activity of synthesized compounds was
evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH)
(Burits and Bucar 2000; Cuendet et al. 1997) and H2O2
radical scavenging assays (Ruch et al. 1989). Ascorbic acid
and BHT were used as standard antioxidants. DPPH radical
scavenging assay results (Table 2) revealed that, com-
pounds 5d, 5h, 6e, and 6j exhibited strong scavenging
ability with potent IC50 values of 09.43 1.20, 14.25
0.54, 12.46 1.56, and 08.34 0.40 µg/mL, respectively.
These values were lower than the standard drugs ascorbic
acid (15.54 0.67 µg/mL) and BHT (17.22 0.21 µg/mL).
It can be observed that the precursor chalcone compounds
5d and 5h comprised of electron rich isopropyl and dime-
thoxy substitutions on phenyl ring, respectively, displayed
potent free radical scavenging ability. However, up on
cyclization, the aurone derivatives 6e and 6j having elec-
tronegative dichloro atoms and indolyl nucleus, respec-
tively, exhibited promising antioxidant activity.
1
unsaturated C=O group. The H-NMR (nuclear magnetic
resonance) spectrum of 6c showed a singlet at δ 6.98 cor-
responds to pyrazole ring proton, a singlet at δ 6.52 due to
Hβ of α,β unsaturated C=O and a quartet at δ 5.02 was due
to O–CH2 protons. The 13C-NMR spectrum of 6c showed a
peak at δ 181.47 corresponds to C=O and δ 66.56 due to
O–CH2 carbon. Similarly the mass spectrum (MS) was
It can be envisaged that substituent with lone pair of
electrons on the aurone scaffold enhanced the radical

Med Chem Res
Table 2 Antioxidant activity of synthesized compounds 5a-j and 6a-j
6633), Staphylococcus aureus (ATCC 29213) as exam-
ples of Gram-positive bacteria and Escherichia coli
(ATCC 11229), Proteus vulgaris (ATCC 29213) as
examples of Gram-negative bacteria. Agar well-diffusion
method was used to assay the antibacterial activity against
test strains on Mueller–Henton agar plates. Gentamicin
was employed as standard antibacterial drug. The results
obtained as minimum inhibitory concentration (MIC) in
µg/mL and measurements are presented in Table 3.
Investigation of the antibacterial efficiency of the syn-
thesized compounds revealed that most of the tested
compounds displayed variable inhibitory effects on the
growth of the tested gram-positive and gram-negative
bacterial strains. It is evident from Table 3, compounds 5b
(Ar = 4-bromophenyl) displayed MIC 3.125 µg/mL
against gram-positive bacteria and 6.25 µg/mL against
gram-negative bacteria, 5e (Ar = 2,4-dichlorophenyl)
exhibited MIC 6.25 µg/mL against most of the bacteria,
6b showed MIC 1.56 µg/mL against S.aureus and 3.125
µg/mL against rest of the bacteria, 6c (Ar = 2-chlor-
ophenyl) displayed 3.125 µg/mL against most of the
bacteria except E.coli (6.25 µg/mL) and 6e with dichloro
substitution exhibited 3.125 µg/mL against all the bac-
teria. It was envisaged from the analysis of antibacterial
activity results that electro-negative atoms such as chloro,
bromo on phenyl ring were found more potent as com-
pared to control drug gentamicin (1.56 µg/mL).
Compound
Scavenging activity (IC50 µg/mL)
DPPH
H2O2
5a
5b
5c
5d
5e
5f
20.25 0.15
18.12 0.54
19.56 0.23
09.43 1.20
23.68 0.02
24.68 0.34
19.65 0.82
14.25 0.54
20.10 0.53
19.45 0.32
19.42 0.38
17.85 1.37
18.62 0.46
17.28 0.65
12.46 1.56
21.10 0.50
22.15 0.43
18.67 0.56
22.46 0.46
08.34 0.40
15.54 0.67
17.22 0.21
22.24 0.25
17.53 0.42
21.28 1.24
16.94 0.11
19.75 1.65
26.19 0.60
21.02 0.24
13.46 0.67
23.44 0.29
24.07 0.40
11.72 0.46
19.05 0.71
18.24 0.49
17.52 1.24
12.21 0.35
22.18 0.75
25.76 0.42
23.52 0.24
24.55 0.43
10.10 0.27
14.65 0.76
16.21 0.14
5g
5h
5i
5j
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
AAa
BHTb
a
b
Ascorbic acid, Butylated hydroxy toluene
Antifungal activity
scavenging potency. It can be justified by the highest
scavenging activity displayed by compound 6j with indolyl
substitution. The remaining compounds showed moderate
activity.
All the title compounds were evaluated for their in vitro
antifungal activity against Aspergillus niger (ATCC 9029)
and Candida albicans (ATCC 10231) fungal strains
(Table 3). Agar well-diffusion method was used to evaluate
the antifungal activity against test strains on PDA plates.
Fluconazole was used as standard antifungal drug. Com-
pound 6b emerged as the promising antifungal agent with
MIC 6.25 µg/mL. Compounds 5b and 6e were able to
induce appreciable promising growth inhibitory activity in
the range of MIC 6.25 µg/mL—12.5 µg/mL when compared
with standard antifungal agent fluconazole (MIC 3.125 µg/
mL). Thus we hypothesized that, compounds with electro-
negative groups such as chloro, bromo on phenyl ring were
exhibited highest antifungal inhibitory potency.
The same series was screened for H2O2 radical scaven-
ging activity (Table 2). As observed from the results, com-
pound 6j emerged as the better radical scavenger with potent
IC50 10.10 0.27 µg/mL. Compounds 5h, 6a, and 6e
exhibited good antioxidant activity with IC50 13.46 0.67,
11.72 0.46, and 12.21 0.35 µg/mL, respectively, with
more scavenging potency than the standard drugs ascorbic
acid (14.65 0.76 µg/mL) and BHT (16.21 0.14 µg/mL).
The rest of the compounds displayed moderate antioxidant
activity. From the antioxidant screening, it can be concluded
that presence of lone pair of electrons on the aurone nucleus
played an important role to exhibit radical scavenging ability.
Molecular docking
Antimicrobial activity
In order to gain more insight in to the interactions of the
most potent compounds towards antioxidant activity, in
silico molecular docking of the title compounds with the
cyclooxygenase-II enzyme was carried out. The best poses
of the docked compound are shown in the Figs. 2 and 3, and
the results are depicted in Table 4. The most potent
Antibacterial activity
The synthesized compounds were screened in vitro for
their antibacterial activity against Bacillus subtilis (ATCC

Med Chem Res
Table 3 Antimicrobial activity
of synthesized compounds
Compound
Gram-positive bacteria
Gram-negative bacteria
Fungal strains
B. subtilis
S. aureus
E. coli
P. vulgaris
A. niger
C. albicans
5a
12.5
3.125
6.25
25
25
12.5
6.25
6.25
12.5
6.25
25
12.5
6.25
12.5
50
25
25
5b
3.125
6.25
25
12.5
25
6.25
25
5c
5d
50
25
5e
6.25
25
3.125
12.5
50
6.25
100
100
50
25
12.5
50
5f
50
5g
100
50
50
>100
>100
50
>100
100
50
5h
50
25
5i
50
25
25
50
5j
25
25
12.5
6.25
3.125
6.25
50
25
>100
>100
6.25
12.5
12.5
6.25
50
>100
>100
6.25
25
6a
12.5
3.125
3.125
12.5
3.125
50
6.25
1.56
3.125
25
12.5
3.125
3.125
25
6b
6c
6d
12.5
12.5
25
6e
3.125
12.5
25
3.125
25
3.125
25
6f
6g
50
100
50
50
100
>100
50
100
>100
25
6h
25
50
25
6i
12.5
12.5
1.56
–
25
25
12.5
25
6j
12.5
1.56
–
25
50
25
Gentamicin
Fluconazole
3.125
–
1.56
–
–
–
3.125
3.125
Fig. 2 Best docked pose of
compound 5d (a) and 6j (b) with
3NM8 (hydrogen bonds are
displayed as green dotted lines)
(color figure online)
Fig. 3 Best docked pose of
compound 5h (a) and ascorbic
acid (b) with 3NM8 (hydrogen
bonds are displayed as green
dotted lines) (color figure
online)

Med Chem Res
Hydrogen
hydrogen bond energy
bonds
Table 4 Dock score of
synthesized compounds
Compound
MolDock
Score
MolDock grid Rerank score Torsions No. of No. of
runs
5a
5b
5c
5d
5e
5f
−120.478
−127.378
−123.514
−139.102
−131.528
−121.974
−129.229
−140.287
−126.777
−124.503
−121.749
−130.576
−126.339
−137.394
−143.02
−119.284
−128.939
−121.877
−141.028
−133.097
−122.439
−128.667
−141.714
−126.449
123.506
−105.359
−110.459
−106.013
−121.169
−115.579
−107.599
−109.339
−121.714
−110.649
−88.7356
−103.262
−106.602
−104.259
−115.04
4
4
4
5
4
4
4
4
4
4
2
2
2
3
2
2
2
4
2
2
2
8
4
1
3
4
2
7
7
1
1
2
5
2
4
5
9
3
3
5
1
9
1
1
1
1
1
0
1
1
1
0
1
0
0
0
0
0
0
0
1
2
6
−2.5
−2.5
−2.49
−2.4778
−2.498
0
5g
5h
5i
−1.0146
−2.5
−1.218
5j
0
6a
6b
6c
6d
6e
6f
−120.542
−121.003
−124.188
−134.185
−140.311
−125.369
−131.801
−1140.972
−122.115
−139.885
−86.9613
−0.3838
0
0
0
−118.817
−106.344
−108.901
−118.882
−107.267
−106.799
−60.8708
0
−127.094
−132.772
−140.181
−128.04
0
6g
6h
6i
0
0
−2.03313
−2.338
−5.193
6j
−137.388
Ascorbic acid −75.7462
antioxidant compounds 5d and 6j displayed the better
MolDock score values −139.102 and −137.388, respec-
tively. The standard drug ascorbic acid exhibited Moldock
score of −86.9613. Most of the compounds showed the
hydrogen bond interactions with one or more amino acid
residues of the active pocket. The amino acids involved
interactions with the compounds Met-215, His-208, Gly-
216, Asn-205, Arg-209, Pro-201, Val-217, Val-218, Ala-
44, Lys-47, Asn-205, His-60, and Val-218.
The compound 5d showed a hydrogen bond interaction
between O atom of keto group with Lys-47 (green dotted
lines) (Fig. 2a). Compound 6j formed three hydrogen
bonds, two hydrogen bonds between O atoms of aurone
ring moiety with Asn-205, Arg-209, and one hydrogen
bond between N atom of indole nucleus with Met-215
(green dotted lines) (Fig. 2b). Compounds 5h and 6e
exhibited relatively less binding affinity with dock score
values of −141.714 and −140.311. Compound 5h formed
one hydrogen bond between O atom of keto group with
Lys-47 (Fig. 3a). Ascorbic acid showed six hydrogen
bonds, O atom of hydroxyl group bonded with Asn-205.
The O atom of methylene group formed three hydrogen
bonds with His-42, His-60, His-208, and another O atom of
methylene group formed two hydrogen bonds with Gly-
216, Val-217 (Fig. 3b). These in silico findings are well
supported by results of antioxidant activity.
Experimental
Chemistry
All melting points were recorded on Stuart SMP3 melting-
point apparatus and are uncorrected. The IR spectra ῦ in
cm−1 (KBr) were recorded on Shimadzu FTIR 8400S
spectrometer. All the microwave irradiation experiments
were performed in a CEM Discover Microwave System and
reaction temperatures were monitored by an equipped IR
1
sensor. The H NMR and 13C NMR spectra were run on
Bruker Avance-400 spectrometer at 400 and 100 MHz,
respectively, using tetramethylsilane as an internal reference
and DMSO-d6 as solvent. The mass spectra were recorded
on Finnigan MAT 1020 mass spectrometer; in m/z.
Elemental analyses were recorded on a Karlo Erba 1106
elemental analyzer. All the reactions were monitored on
silica gel percolated TLC plates of Merck 60 F254 and spots
were visualized with UV light.
General procedure for the synthesis of compounds (5a–j)
Conventional method
To a stirred solution of 1-(5-hydroxy-2H-chromen-6-yl)-
ethanone (3) (0.1 g, 0.52 mmol), KOH (1.04 mmol) in

Med Chem Res
ethanol (20 mL), was added substituted aromatic aldehydes
(4a–j) (0.52 mmol) and refluxed for 10–24 h. Progress of
the reaction was monitored by TLC (EtOAc:hexane
1:5 v/v). After completion of the reaction, reaction mixture
was poured into ice cold water and neutralized with 10%
dil. HCl solution. The solid was filtered and recrystallized
from ethanol to get the pure compound.
(E)-3-(2-chlorophenyl)-1-(5-hydroxy-2H-chromen-6-yl)
prop-2-en-1-one (5c) Pale yellow solid; yield (89%); m.p.
118–120 °C; IR (KBr) (cm−1): 3062 (OH), 2938 (H–C=),
1636 (α,β-unsaturated C=O); 1H-NMR (400 MHz, DMSO-
d6) δ p.p.m.: 13.62 (s, 1H, OH), 8.26 (dd, 1H, Ar–H), 8.21
(d, 1H, J = 8.92 Hz, Ar–H), 8.14 (d, 1H, J = 15.40 Hz, Hβ),
8.05 (d, 1H, J = 15.40 Hz, Hα), 7.58 (m, 1H, Ar–H), 7.48
(m, 2H, Ar–H), 6.69 (d, 1H, J = 10.14 Hz, Ar–CH=C),
6.45 (d, 1H, J = 8.92 Hz, Ar–H), 5.87 (m, 1H, Ar–C=CH),
4.93 (q, 2H, OCH2); 13C-NMR (100 MHz, DMSO-d6) δ p.
p.m.: 191.6 (C=O), 160.4 (C8a), 159.7 (C5), 138.6 (Cβ),
134.4 (C1′), 132.4, 132.0 (C4′, C5′), 131.9 (C6′), 129.9 (C2′),
128.6 (C7), 127.5 (C3′), 123.4 (C3), 120.6 (C4), 116.7 (Cα),
113.9 (C6), 109.4 (C4a), 107.6 (C8), 65.8 (OCH2); LC-MS
(m/z): 313 (M + H)+. Elemental analysis (C18H13ClO3):
calcd. C, 69.13; H, 4.19. found: C, 69.33; H, 4.41%.
Microwave irradiation method
To a mixture of 1-(5-hydroxy-2H-chromen-6-yl)-ethanone
(3) (0.1 g, 0.52 mmol) and substituted aromatic aldehydes
(4a–j) (0.52 mmol) in ethanol (5 mL), powdered KOH
(1.04 mmol) was added and subjected to microwave irra-
diation at 180 W for 4–7 min. Progress of the reaction was
monitored by TLC (EtOAc:hexane 1:5 v/v). After comple-
tion of the reaction, reaction mixture was poured into ice
cold water and neutralized with 10% dil. HCl solution. The
solid was filtered and recrystallized from ethanol to get the
pure compound.
(E)-1-(5-hydroxy-2H-chromen-6-yl)-3-(4-isopropylphenyl)
prop-2-en-1-one (5d) Yellow solid; yield (94%); m.p.:
72–74 °C; IR (KBr) (cm−1): 3053 (OH), 2959 (H–C=),
1636 (α,β-unsaturated C=O); 1H-NMR (400 MHz, DMSO-
d6) δ p.p.m.: 13.86 (s, 1H, OH), 8.19 (d, 1H, J = 9.06 Hz,
Ar–H), 7.94 (s, 1H, J = 15.48 Hz, Hβ), 7.82 (t, 3H, Ar–H),
7.34 (d, 2H, J = 8.12 Hz, Ar–H), 6.70 (d, 1H, J = 10.19 Hz,
Ar–CH=C), 6.44 (d, 1H, J = 8.87 Hz, Ar–H), 5.86 (m, 1H,
Ar–C=CH), 4.92 (q, 2H, OCH2), 2.94 (m, 1H, CH), 1.22
(d, 6H, J = 6.98 Hz, 2 × CH3); 13C-NMR (100 MHz,
DMSO-d6) δ p.p.m.: 191.8 (C=O), 159.9 (C8a), 159.4 (C5),
151.4 (Cβ), 144.2 (C1′), 131.9 (C4′), 131.8 (C7), 128.9,
126.5 (C2′, C3′), 120.3 (C3), 119.4 (C4), 116.5 (Cα), 113.7
(C6), 109.1 (C4a), 107.2 (C8), 65.5 (OCH2), 33.0 (CH), 23.2
(2 C, 2 × CH3); LC-MS (m/z): 321 (M + H)+. Elemental
analysis (C21H20O3): calcd. C, 78.73; H, 6.29. found: C,
78.52; H, 6.50%.
(E)-1-(5-hydroxy-2H-chromen-6-yl)-3-phenylprop-2-en-1-
one (5a) Pale yellow solid; yield (91%); m.p.: 102–103 °
C; IR (KBr) (cm−1): 3056 (OH), 2927 (H–C=), 1636 (α,β-
1
unsaturated C=O); H-NMR (400 MHz, DMSO-d6) δ p.p.
m.: 13.61 (s, 1H, OH), 7.88 (d, 1H, J = 15.48 Hz, Hβ), 7.71
(d, 1H, J = 8.87 Hz, Ar–H), 7.64 (m, 2H, Ar–H), 7.55 (d,
1H, J = 15.48 Hz, Hα), 7.42 (t, 3H, Ar–H), 6.82 (d, 1H, J
= 10.19 Hz, Ar–CH = C), 6.37 (d, 1H, J = 8.87 Hz, Ar–H),
5.72 (m, 1H, Ar–C = CH), 4.91 (q, 2H, OCH2); 13C-NMR
(100 MHz, DMSO-d6) δ p.p.m.: 192.1 (C=O), 160.2 (C8a),
159.7 (C5), 144.3 (Cβ), 134.3 (C1′), 132.2 (C4′), 130.7 (C7),
129.0, 128.8 (C2′, C3′), 120.7 (C3), 120.5 (C4), 116.8 (Cα),
113.9 (C6), 109.4 (C4a), 107.5 (C8), 65.8 (OCH2); LC-MS
(m/z): 279 (M + H)+. Elemental analysis (C18H14O3): calcd.
C, 77.68; H, 5.07. found: C, 77.90; H, 4.83%
(E)-3-(4-bromophenyl)-1-(5-hydroxy-2H-chromen-6-yl)
prop-2-en-1-one (5b) Yellow solid; yield (88%); m.p.:
170–172 °C; IR (KBr) (cm−1): 3058 (OH), 2934 (H–C=),
1635 (α,β-unsaturated C=O); 1H-NMR (400 MHz, DMSO-
d6) δ p.p.m.: 13.74 (Broad-s, 1H, OH), 8.20 (d, 1H, J =
8.92 Hz, Ar–H), 8.07 (d, 1H, J = 15.40 Hz, Hβ), 7.88 (d,
2H, J = 8.55 Hz, Ar–H), 7.79 (d, 1H, J = 15.40 Hz, Hα),
7.67 (d, 2H, J = 8.43 Hz, Ar–H), 6.69 (d, 1H, J = 10.14 Hz,
Ar–CH=C), 6.42 (d, 1H, J = 8.80 Hz, Ar–H), 5.86 (m, 1H,
Ar–C=CH), 4.92 (q, 2H, OCH2); 13C-NMR (100 MHz,
DMSO-d6) δ p.p.m.: 190.1 (C=O); 160.2 (C8a), 157.0 (C5),
138.8 (Cβ), 132.9 (C1′), 132.3 (C4′), 131.9 (C7), 131.4,
129.0 (C2′, C3′), 127.7 (C3), 122.1 (C4), 117.5 (Cα), 115.4
(C6), 110.6 (C4a), 107.9 (C8), 66.0 (OCH2); LC-MS (m/z):
357 (M + H)+. Elemental analysis (C18H13BrO3): calcd. C,
60.52; H, 3.67. found: C, 60.31; H, 3.98%.
(E)-3-(2,4-dichlorophenyl)-1-(5-hydroxy-2H-chromen-6-yl)
prop-2-en-1-one (5e) Yellow solid; yield (86%); m.p.:
128–130 °C; IR (KBr) (cm−1): 3068 (OH), 2946 (H–C=),
1633 (α,β-unsaturated C=O); 1H-NMR (400 MHz, DMSO-
d6) δ p.p.m.: 13.57 (s, 1H, OH), 8.28 (d, 1H, J = 8.49 Hz,
Ar–H), 8.20 (d, 1H, J = 8.87 Hz, Ar–H), 8.05 (s, 2H,
Ar–H), 7.75 (s, 1H, Ar–H), 7.75 (d, 1H, J = 8.49 Hz,
Ar–H), 6.68 (d, 1H, J = 10.00 Hz, Ar–CH=C), 6.44 (d, 1H,
J = 8.68 Hz, Ar–H), 5.87 (m, 1H, Ar–C=CH), 4.92 (q, 2H,
OCH2); 13C-NMR (100 MHz, DMSO-d6) δ p.p.m.: 191.5
(C=O), 160.6 (C8a), 159.7 (C5), 137.4 (Cβ), 135.8, 135.2
(2C, C1′, C2′), 132.5 (Ar–C), 131.0 (C7), 129.9, 129.5,
127.9 (3C, Ar–C), 124.1 (C3), 120.8 (C4), 116.7 (Cα), 114.0
(C6), 109.4 (C4a), 107.8 (C8), 65.9 (OCH2); LC-MS (m/z):
347 (M + H)+. Elemental analysis (C18H12Cl2O3): calcd. C,
62.27; H, 3.48. found: C, 62.49; H, 3.66%.

Med Chem Res
(E)-1-(5-hydroxy-2H-chromen-6-yl)-3-(p-tolyl)prop-2-en-
1-one (5f) Wine red solid; yield (93%); m.p.: 116–118 °C;
IR (KBr) (cm−1): 3072 (OH), 2955 (H–C=), 1636 (α,β-
°C; IR (KBr) (cm−1): 3075 (OH), 2965 (H–C=), 1639 (α,β-
unsaturated C=O); H-NMR (400 MHz, DMSO-d6) δ p.p.
1
m.: 13.64 (s, 1H, OH), 8.00 (d, 1H, J = 15.10 Hz, Hβ), 7.68
(d, 1H, J = 8.87 Hz, Ar–H), 7.38 (m, 3H, Ar–H), 7.10 (m,
1H, Ar–H), 6.83 (d, 1H, J = 10.19 Hz, Ar–CH=C), 6.37 (d,
1H, J = 8.87 Hz, Ar–H), 5.73 (m, 1H, Ar–C=CH), 4.92 (q,
2H, OCH2); 13C-NMR (100 MHz, DMSO-d6) δ p.p.m.:
192.1 (C=O), 160.2 (C8a), 159.6 (C5), 141.0 (C1′), 139.2
(Cβ), 132.8 (C4′), 130.1 (C7), 129.9, 129.3 (2C, Ar–C),
128.0 (Cα), 124.1 (C3), 120.8 (C4), 113.6 (C6), 109.6 (C4a),
107.5 (C8), 65.2 (OCH2); LC-MS (m/z): 285 (M + H)+.
Elemental analysis (C16H12O3S): calcd. C, 67.59; H, 4.25.
found: C, 67.78; H, 4.56%.
1
unsaturated C=O); H-NMR (400 MHz, DMSO-d6) δ p.p.
m.: 13.86 (s, 1H, OH), 8.18 (d, 1H, J = 8.87 Hz, Ar–H),
7.93 (s, 1H, J = 15.48 Hz, Hβ), 7.80 (m, 3H, Ar–H), 7.27 (d,
2H, J = 7.93 Hz, Ar–H), 6.68 (d, 1H, J = 10.19 Hz,
Ar–CH=C), 6.42 (d, 1H, J = 8.87 Hz, Ar-H), 5.85 (m, 1H,
Ar–C=CH), 4.90 (q, 2H, OCH2), 2.34 (s, 3H, Ar–CH3);
13C-NMR (100 MHz, DMSO-d6) δ p.p.m.: 192.2 (C=O),
160.2 (C8a), 159.7 (C5), 144.5 (Cβ), 141.0 (C4′), 132.2 (C1′),
131.7 (C7), 129.5, 129.1 (C2′, C3′), 120.6 (C3), 119.6 (C4),
116.8 (Cα), 114.0 (C6), 109.5 (C4a), 107.6 (C8), 65.8
(OCH2), 21.0 (Ar–CH3); LC-MS (m/z): 293 (M + H)+.
Elemental analysis (C19H16O3): calcd. C, 78.06; H, 5.52.
found: C, 78.24; H, 5.31%.
(E)-1-(5-hydroxy-2H-chromen-6-yl)-3-(1H-indol-3-yl)
prop-2-en-1-one (5j) Red solid; yield (89%); m.p.:
178–180 °C; IR (KBr) (cm−1): 3075 (OH), 3049 (NH),
2965 (H–C=), 1631 (α,β-unsaturated C=O); 1H-NMR
(400 MHz, DMSO-d6) δ p.p.m.: 11.58 (s, 1H, OH), 8.10
(d, 1H, J = 15.10 Hz, Hβ), 7.91 (m, 1H, Ar–H), 7.78 (m,
3H, Ar–H), 7.49 (d, 1H, J = 15.10 Hz, Hα), 7.42 (m, 1H,
Ar–H), 7.18 (m, 2H, Ar–H), 6.70 (d, 1H, J = 10.19 Hz,
Ar–CH=C), 6.32 (d, 1H, J = 8.68 Hz, Ar–H), 5.69 (m, 1H,
Ar–C=CH), 4.83 (q, 2H, OCH2); 13C-NMR (100 MHz,
DMSO-d6) δ p.p.m.: 192.3 (C=O), 160.7 (C8a), 160.2 (C5),
138.4 (Cβ), 137.2, 130.5 (2C, Ar–C), 130.3 (C7), 128.4
(Cα), 125.3 (C3), 123.6, 121.9 (2C, Ar–C), 120.7 (C4),
118.9, 118.5, 115.7 (3C, Ar–C), 114.7 (C6), 111.9 (C4a),
107.4 (C8), 103.9 (Ar–C), 66.1 (OCH2); LC-MS (m/z): 318
(M + H)+. Elemental analysis (C20H15NO3): calcd. C,
75.70; H, 4.76; N, 4.41. found: C, 75.39; H, 4.97; N, 4.61%.
(E)-1-(5-hydroxy-2H-chromen-6-yl)-3-(4-methoxyphenyl)
prop-2-en-1-one (5g) Orange solid; yield (91%); m.p.:
112–114 °C; IR (KBr) (cm−1): 3063 (OH), 2943 (H–C=),
1635 (α,β-unsaturated C=O); 1H-NMR (400 MHz, DMSO-
d6) δ p.p.m.: 13.98 (s, 1H, OH), 8.16 (d, 1H, J = 8.87 Hz,
Ar–H), 7.85 (m, 4H, Ar–H), 7.02 (d, 2H, J = 8.87 Hz,
Ar–H), 6.70 (d, 1H, J = 10.19 Hz, Ar–CH=C), 6.42 (d, 1H,
J = 8.68 Hz, Ar–H), 5.85 (m, 1H, Ar–C=CH), 4.90 (q, 2H,
OCH2), 3.83 (s, 3H, OCH3); 13C-NMR (100 MHz, DMSO-
d6) δ p.p.m.: 192.0 (C=O), 161.5 (C8a), 160.0 (C5), 159.7
(C4′), 144.4 (Cβ), 131.9 (C1′), 131.0 (Ar–C), 127.0 (C7),
120.3 (C3), 117.9 (C4), 116.9 (Cα), 114.3 (Ar–C), 114.0
(C6), 109.4 (C4a), 107.4 (C8), 65.7 (OCH2), 55.2 (OCH3);
LC-MS (m/z): 309 (M + H)+. Elemental analysis
(C19H16O4): calcd. C, 74.01; H, 5.23. found: C, 74.20; H,
5.01%.
General procedure for the synthesis of compounds (6a–j)
(E)-3-(3,4-dimethoxyphenyl)-1-(5-hydroxy-2H-chromen-6-
yl)prop-2-en-1-one (5h) Orange solid; yield (91%); m.p.:
88–90 °C; IR (KBr) (cm−1): 3060 (OH), 2939 (H–C=),
1632 (α,β-unsaturated C=O); 1H-NMR (400 MHz, DMSO-
d6) δ p.p.m.: 13.85 (s, 1H, OH), 8.05 (d, 1H, J = 8.87 Hz,
Ar–H), 7.83 (d, 1H, J = 15.49 Hz, Hβ), 7.18 (m, 3H, Ar–H),
6.84 (d, 1H, J = 8.72 Hz, Ar–H), 6.71 (d, 1H, J = 10.19 Hz,
Ar–CH=C), 6.45 (d, 1H, J = 8.87 Hz, Ar–H), 5.85 (m, 1H,
Ar–C=CH), 4.91 (q, 2H, OCH2), 3.86, 3.82 (s, 6H,
(OCH3)2); 13C-NMR (DMSO-d6) δ p.p.m.: 192.1 (C=O),
160.0 (C8a), 159.7 (C5), 151.5, 148.9 (C3′, C4′), 144.9 (Cβ),
132.1 (C1′), 132.0 (C7), 127.2 (C3), 120.5 (C4), 118.0
(Ar–C), 116.9 (Cα), 114.0 (C6), 110.8, 110.7 (Ar–C), 109.4
(C4a), 107.3 (C8), 65.7 (OCH2), 55.7, 55.5 (2C,OCH3); LC-
MS (m/z): 339 (M + H)+. Elemental analysis (C20H18O5):
calcd. C, 70.99; H, 5.36. found: C, 70.78; H, 5.57%.
Conventional method
To a well stirred solution of (E)-3-(aryl)-1-(5-hydroxy-2H-
chromen-6-yl)prop-2-en-1-ones (5a–j) (0.5 mmol) in pyr-
idine (20 mL), Hg(OAc)2 (0.5 mmol) was added and the
reaction mixture was refluxed for 4–5 h. After completion of
the reaction, the cooled mixture was poured into ice cold
water and acidified with HCl aqueous solution (30%, v/v).
The precipitate was extracted with CH2Cl2 and dried over
Mg2SO4. After CH2Cl2 was evaporated, the residue was
recrystallized from ethanol to give compounds 6a–j.
Microwave irradiation method
A mixture of (E)-3-(aryl)-1-(5-hydroxy-2H-chromen-6-yl)
prop-2-en-1-ones (5a–j) (0.5 mmol) and Hg(OAc)2 (0.5
mmol) in pyridine (5 mL) was subjected to microwave
irradiation at 180 W for 3–5 min. After completion of the
reaction, the cooled mixture was poured into ice cold water
(E)-1-(5-hydroxy-2H-chromen-6-yl)-3-(thiophen-2-yl)prop-
2-en-1-one (5i) Yellow solid; yield (87%); m.p.: 101–102

Med Chem Res
1
and acidified with HCl aqueous solution (30%, v/v). The
precipitate was extracted with CH2Cl2 and dried over
Mg2SO4. After CH2Cl2 was evaporated, the residue was
recrystallized from ethanol to give compounds 6a–j.
unsaturated C=O); H-NMR (400 MHz, DMSO-d6) δ p.p.
m.: 7.90 (d, 2H, J = 8.03 Hz, Ar–H), 7.53 (d, 1H, J = 8.28
Hz, Ar–H), 7.38 (d, 2H, J = 8.03 Hz, Ar–H), 6.83 (m, 2H,
Ar–CH=C, Hβ), 6.67 (d, 1H, J = 8.28 Hz, Ar–H), 6.06 (m,
1H, Ar–C = CH), 5.03 (s, 2H, OCH2), 2.94 (m, 1H, CH),
1.23 (d, 6H, J = 6.77 Hz, 2 × CH3); 13C-NMR (100 MHz,
DMSO-d6) δ p.p.m.: 181.4 (C=O), 161.3 (C5a), 160.8 (C2),
150.6 (C4′), 146.8 (Cα), 131.4 (2C, Ar–C), 129.4 (C1′),
127.0 (2C, Ar–C), 124.8 (C4), 123.2 (C8), 115.3 (C9), 114.6
(C3), 112.4 (Cβ), 111.5 (C5), 106.7 (C9a), 66.3 (OCH2), 33.3
(CH), 23.5 (2C, 2×CH3); LC-MS (m/z): 319 (M + H)+.
Elemental analysis C21H18O3: calcd. C, 79.22; H, 5.70.
found: C, 79.43; H, 5.44%.
(Z)-2-benzylidene-2H-furo[2,3-f]chromen-3(7H)-one
(6a) Pale yellow solid; yield (81%); m.p.: 138–140 °C; IR
(KBr) (cm−1): 2960 (H–C=), 1687 (α,β-unsaturated C=O);
1H-NMR (400 MHz, DMSO-d6) δ p.p.m.: 7.88 (d, 2H, J =
8.30 Hz, Ar–H), 7.55 (d, 1H, J = 8.49 Hz, Ar–H), 7.43 (m,
3H, Ar–H), 6.81 (m, 2H, Hβ, Ar–CH=C), 6.61 (d, 1H, J =
8.49 Hz, Ar–H), 5.88 (m, 1H, Ar–C=CH), 5.02 (q, 2H,
OCH2); 13C-NMR (100 MHz, DMSO-d6) δ p.p.m.: 181.4
(C=O), 161.4 (C5a), 160.9 (C2), 147.1 (Cα), 131.8 (C1′),
131.2 (2C, Ar–C), 129.7 (Ar–C), 128.9 (2C, Ar–C), 124.8
(C4), 123.2 (C8), 115.3 (C9), 114.4 (C3), 112.5 (Cβ), 111.2
(C5), 106.7 (C9a), 66.3 (OCH2); LC-MS (m/z): 277 (M +
H)+. Elemental analysis (C18H12O3): calcd. C, 78.25; H,
4.38; found: C, 78.48; H, 4.16%.
(Z)-2-(2,4-dichlorobenzylidene)-2H-furo[2,3-f]chromen-3
(7H)-one (6e) Pale yellow solid; yield (75%); m.p.:
253–256 °C; IR (KBr) (cm−1): 2957 (H–C=), 1697 (α,β-
1
unsaturated C=O); H-NMR (400 MHz, DMSO-d6) δ p.p.
m.: 8.34 (d, 1H, J = 8.53 Hz, Ar–H), 7.82 (d, 1H, Ar–H),
7.60 (m, 2H, Ar–H), 6.95 (s, 1H, Hβ), 6.85 (d, 1H, J =
10.29 Hz, Ar–CH=C), 6.72 (d, 1H, J = 8.53 Hz, Ar–H),
6.08 (m, 1H, Ar–C=CH), 5.06 (s, 2H, OCH2); 13C-NMR
(100 MHz, DMSO-d6) δ p.p.m.: 181.6 (C=O), 161.7 (C5a),
161.4 (C2), 148.2 (Cα), 134.4 (C2′), 132.0, 131.3, 130.0,
129.4, 128.1 (5C, Ar–C), 125.3 (C4), 123.6 (C8), 115.3
(C9), 114.2 (C3), 112.9 (Cβ), 106.9 (C9a), 105.2 (C5), 66.6
(OCH2); LC-MS (m/z): 345 (M + H)+. Elemental analysis
(C18H10Cl2O3): calcd. C, 62.63; H, 2.92. found: C, 62.81;
H, 2.71%.
(Z)-2-(4-bromobenzylidene)-2H-furo[2,3-f]chromen-3(7H)-
one (6b) Pale yellow solid; yield (78%); m.p.: 237–240 °
C; IR (KBr) (cm−1): 2959 (H–C=), 1688 (α,β-unsaturated
1
C=O); H-NMR (400 MHz, DMSO-d6) δ p.p.m.: 7.92 (d,
2H, J = 8.53 Hz, Ar–H), 7.70 (d, 2H, J = 8.53 Hz, Ar–H),
7.56 (d, 1H, J = 8.28 Hz, Ar–H), 6.87 (m, 2H, Ar–CH=C,
Hβ), 6.70 (d, 1H, J = 8.28 Hz, Ar–H), 6.07 (m, 1H,
Ar–C=CH), 5.04 (q, 2H, OCH2); 13C-NMR (100 MHz,
DMSO-d6) δ p.p.m.: 181.9 (C=O), 161.8 (C5a), 161.1 (C2),
147.7 (Cα), 131.9 (C1′), 131.1 (2C, Ar–C), 128.8 (Ar–C),
129.3 (2C, Ar–C), 124.9 (C4), 123.6 (C8), 116.0 (C9), 115.2
(C3), 114.1 (Cβ), 111.7 (C5), 106.9 (C9a), 66.3 (OCH2); LC-
MS (m/z): 355 (M + H)+. Elemental analysis
(C18H11BrO3): calcd. C, 60.87; H, 3.12. found: C, 60.66; H,
3.30%.
(Z)-2-(4-methylbenzylidene)-2H-furo[2,3-f]chromen-3
(7H)-one (6f) Pale yellow solid; yield (83%); m.p.:
194–196 °C; IR (KBr) (cm−1): 2961 (H–C=), 1697 (α,β-
1
unsaturated C=O); H-NMR (400 MHz, DMSO-d6) δ p.p.
m.: 7.88 (d, 2H, J = 8.19 Hz, Ar–H), 7.55 (d, 1H, J = 8.31
Hz, Ar–H), 7.33 (d, 2H, J = 8.06 Hz, Ar–H), 7.27 (d, 1H, J
= 8.06 Hz, Ar–H), 6.84 (s, 1H, Hβ), 6.70 (dd, 1H,
Ar–CH=C), 6.08 (m, 1H, Ar–C=CH), 5.04 (q, 2H, OCH2),
2.37 (s, 3H, Ar–CH3); 13C-NMR (100 MHz, DMSO-d6) δ
p.p.m.: 181.4 (C=O), 161.3 (C5a), 160.8 (C2), 146.6 (Cα),
139.9 (C4′), 131.2 (2C, Ar–C), 129.6 (2C, Ar–C), 129.0
(Ar–C), 124.8 (C4), 123.3 (C8), 115.4 (C9), 114.6 (C3),
112.4 (Cβ), 111.5 (C5), 106.7 (C9a), 66.3 (OCH2), 21.0
(Ar–CH3); LC-MS (m/z): 291 (M + H)+. Elemental analy-
sis (C19H14O3): calcd. C, 78.61; H, 4.86. found: C, 78.82;
H, 4.62%.
(Z)-2-(2-chlorobenzylidene)-2H-furo[2,3-f]chromen-3(7H)-
one (6c) Pale yellow solid; yield (80%); m.p.: 176–179 °
C; IR (KBr) (cm−1): 2959 (H–C=), 1699 (α,β-unsaturated
1
C=O); H-NMR (400 MHz, DMSO-d6) δ p.p.m.: 8.29 (dd,
1H, Ar–H), 7.50 (m, 4H, Ar–H), 6.98 (s, 1H, Hβ), 6.78 (dd,
1H, Ar–CH=C), 6.68 (d, 1H, J = 8.28 Hz, Ar–H), 6.03 (m,
1H, Ar–C=CH), 5.02 (q, 2H, OCH2); 13C-NMR (100 MHz,
DMSO-d6) δ p.p.m.: 181.4 (C=O), 161.6 (C5a), 161.3 (C2),
148.1 (Cα), 134.3, 131.9, 131.2, 129.9, 129.3, 128.0 (6C,
Ar–C), 125.2 (C4), 123.5 (C8), 115.3 (C9), 114.1 (Cβ),
112.8 (C3), 106.8 (C5), 105.1 (C9a), 66.5 (OCH2); LC-MS
(m/z): 310 (M + H)+. Elemental analysis (C18H11ClO3):
calcd. C, 69.58; H, 3.57. found: C, 69.76; H, 3.37%.
(Z)-2-(4-methoxybenzylidene)-2H-furo[2,3-f]chromen-3
(7H)-one (6g) Pale yellow solid; yield (82%); m.p.:
120–122 °C; IR (KBr) (cm−1): 2960 (H–C=), 1691 (α,β-
1
(Z)-2-(4-isopropylbenzylidene)-2H-furo[2,3-f]chromen-3
(7H)-one (6d) Pale yellow solid; yield (83%); m.p.:
196–198 °C; IR (KBr) (cm−1): 2961 (H–C=), 1696 (α,β-
unsaturated C=O); H-NMR (400 MHz, DMSO-d6) δ p.p.
m.: 7.86 (d, 2H, J = 7.36 Hz, Ar–H), 7.49 (d, 1H, J = 7.93
Hz, Ar–H), 7.01 (d, 2H, J = 7.55 Hz, Ar–H), 6.80 (m, 2H,

Med Chem Res
Ar–CH=C, Hβ), 6.62 (d, 1H, J = 7.93 Hz, Ar–H), 5.96 (d,
1H, J = 9.06 Hz, Ar–C=CH), 5.04 (s, 2H, OCH2), 3.87 (s,
3H, OCH3); 13C-NMR (100 MHz, DMSO-d6) δ p.p.m.:
181.2 (C=O), 161.1 (C5a), 160.6 (C4′), 160.5 (C2), 145.9
(Cα), 133.2 (2C, Ar–H), 124.7 (C4), 124.6 (C8), 124.3 (C1′),
123.2 (C9), 115.4 (C3), 114.5 (2C, Ar–C), 113.8 (Cβ), 112.3
(C5), 106.7 (C9a), 66.3 (OCH2), 55.2 (OCH3); LC-MS (m/
z): 307 (M + H)+. Elemental analysis (C19H14O4): calcd. C,
74.50; H, 4.61. found: C, 74.72; H, 4.39%.
137.1, 129.1 (2 C, Ar–C), 128.3 (C4), 125.8 (C8), 122.8,
121.1 (2 C, Ar–C), 121.0 (C9), 120.1 (C3), 119.5 (Cβ),
119.1, 118.4, 115.0 (3 C, Ar–C), 114.1 (C5), 109.1 (C9a),
104.1 (Ar–C), 66.1 (OCH2); LC-MS (m/z): 316 (M + H)+.
Elemental analysis (C20H13NO3): calcd. C, 76.18; H, 4.16;
N, 4.44. found: C, 76.37; H, 4.37; N, 4.20%.
Biological assay
(Z)-2-(3,4-dimethoxybenzylidene)-2H-furo[2,3-f]chromen-
3(7H)-one (6h) Pale yellow solid; yield (81%); m.p.:
96–98 °C; IR (KBr) (cm−1): 2951 (H–C=), 1687 (α,β-
DPPH radical scavenging activity
The hydrogen atom or electron donation ability of the
compounds was measured from the bleaching of the purple
colored methanol solution of DPPH. The spectro-
photometric assay uses the stable radical DPPH as a
reagent. 1 mL of various concentrations of the test com-
pounds (5, 10, 25, 50, and 100 µg/mL) in methanol was
added to 4 mL of 0.004% (w/v) methanol solution of DPPH.
After a 30 min incubation period at room temperature, the
absorbance was read against blank at 517 nm. The percent
of inhibition of free radical production from DPPH was
calculated by the following equation.
1
unsaturated C=O); H-NMR (400 MHz, DMSO-d6) δ p.p.
m.: 8.18 (d, 1H, J = 9.00 Hz, Ar–H), 7.81 (m, 2H, Ar–H),
7.55 (s, 1H, Hβ), 7.01 (d, 1H, J = 8.39 Hz, Ar–H), 6.68 (d,
1H, J = 10.07 Hz, Ar–CH=C), 6.41 (d, 1H, J = 8.85 Hz,
Ar–H), 5.84 (m, 1H, Ar–C=CH), 4.90 (s, 2H, OCH2), 3.86,
3.81 (s, 6H, (CH3)2); 13C-NMR (100 MHz, DMSO-d6) δ p.
p.m.: 181.1 (C=O), 160.9 (C5a), 160.8, 160.7 (C3′, C4′),
160.3 (C2), 144.7 (Cα), 127.4 (C4), 126.2 (C8), 124.3, 124.0
(2C, Ar–C), 124.0 (C9), 114.5 (C3), 113.8 (Cβ), 112.5
(Ar–C), 112.3 (C5), 111.5 (Ar–C), 105.4 (C9a), 65.9
(OCH2), 55.1 (2C, 2×OCH3); LC-MS (m/z): 337 (M +
H)+. Elemental analysis (C20H16O5): calcd. C, 71.42; H,
4.79. found: C, 71.65; H, 4.60%.
ÂÀ
Á
Ã
% of scavenging ¼ Acontrol ꢀ Asample =Ablank ꢁ 100
% of scavenging ¼ ½ðA control ꢀ A sampleÞ=A blankꢂ
ꢁ 100
(Z)-2-(thiophen-2-ylmethylene)-2H-furo[2,3-f]chromen-3
(7H)-one (6i) Pale yellow solid; yield (82%); m.p.:
142–144 °C; IR (KBr) (cm−1): 2953 (H–C=), 1686 (α,β-
ð1Þ
where Acontrol is the absorbance of the control reaction
(containing all reagents except the test compound) and
Asample is the absorbance of the test compound. Tests were
carried at in triplicate.
1
unsaturated C=O); H-NMR (400 MHz, DMSO-d6) δ p.p.
m.: 8.26 (d, 1H, J = 7.78 Hz, Ar–H), 7.55 (dd, 1H, Ar–H),
7.50 (d, 1H, J = 8.28 Hz, Ar–H), 7.43 (m, 1H, Ar–H), 6.95
(s, 1H, Hβ), 6.75 (d, 1H, J = 10.03 Hz, Ar–CH=C), 6.35 (d,
1H, J = 8.28 Hz, Ar–H), 6.00 (m, 1H, Ar–C=CH), 4.99 (q,
2H, OCH2); 13C-NMR (100 MHz, DMSO-d6) δ p.p.m.:
183.9 (C=O), 154.9 (C5a), 150.5 (C2), 147.9 (Cα), 136.7,
131.5, 131.1, 128.6 (4 C, Ar–C), 127.3 (C4), 123.2 (C8),
121.6 (C9), 121.0 (C3), 117.8 (Cβ), 113.5 (C5), 107.3 (C9a),
65.9 (OCH2); LC-MS (m/z): 283 (M + H)+. Elemental
analysis (C16H10O3S): calcd. C, 68.07; H, 3.57. found: C,
68.29; H, 3.36%.
Hydrogen peroxide (H2O2) scavenging activity
The H2O2 scavenging ability of the compounds was deter-
mined according to the method of Ruch et al., A solution of
H2O2 (40 mM) was prepared in phosphate buffer (pH 7.4).
5, 10, 25, 50, and 100 µg/mL concentrations of the test
compounds in 3.4 mL phosphate buffer were added to H2O2
solution (0.6 mL, 40 mM). The absorbance value of the
reaction mixture was recorded at 230 nm. The percent of
scavenging of H2O2 was calculated using Eq. (1).
(Z)-2-((1H-indol-3-yl)methylene)-2H-furo[2,3-f]chromen-3
(7H)-one (6j) Red solid; yield (79%); m.p.: 253–256 °C;
IR (KBr) (cm−1): 2965 (H–C=), 1692 (α,β-unsaturated
Antimicrobial activity
1
C=O); H-NMR (400 MHz, DMSO-d6) δ p.p.m.: 9.87 {s,
1H, NH), 7.97 (d, 2H, J = 8.69 Hz, Ar–H), 7.52 (d, 1H, J =
8.39 Hz, Ar–H), 7.07 (m, 2H, Ar–H), 7.02 (m, 1H, Ar–H),
6.87 (d, 1H, J = 10.80 Hz, Ar–CH=C), 6.83 (s, 1H, Hβ),
6.67 (d, 1H, J = 8.54 Hz, Ar–H), 6.05 (m, 1H, Ar–C=CH),
5.03 (q, 2H, OCH2); 13C-NMR (100 MHz, DMSO-d6) δ p.
p.m.: 181.8 (C=O), 156.2 (C5a), 152.4 (C2), 145.3 (Cα),
The in vitro antimicrobial studies were carried out by agar
well-diffusion method against test organisms (Chung et al.
1990; Azoro 2002). Nutrient broth (NB) plates were
swabbed with 24 h old broth culture (100 mL) of test bac-
teria. Using the sterile cork borer, wells (6 mm) were made
into each petriplate. The different concentrations of test

Med Chem Res
samples dissolved in DMSO were added into the wells by
using sterile pipettes. Simultaneously, the standard anti-
biotics, gentamicin for antibacterial activity, fluconazole for
antifungal activity were tested against the pathogens. The
plates were incubated at 37 °C for 24 h for bacteria and at
28 °C for 48 h for fungi. After appropriate incubation, the
diameter of zone of inhibition of each well was measured.
Duplicates were maintained and the average values were
calculated for eventual antibacterial activity. Broth dilution
test was used to determine MIC of the above mentioned
samples (Janovska et al. 2003; Bishnu et al. 2009). Freshly
prepared NB was used as diluents. The 24 h old culture of
the test bacteria B. subtilis, S. aureus, E. coli, and P. vul-
garis and the test fungi A. niger and C. albicans were
diluted 100 folds in NB (100 mL bacterial cultures in10 mL
NB). Increasing concentrations of the test samples were
added to the test tubes containing the bacterial and fungal
cultures. All the tubes were incubated at 37 °C for 24 h for
bacteria and at 28 °C for 48 h for fungi. The tubes were
examined for visible turbidity and using NB as control. The
lowest concentration that inhibited visible growth of the
tested organisms was recorded as MIC.
radical and the compounds 5h, 6a, 6e, and 6j were exhibited
better radical scavenging ability with H2O2 radical. Anti-
microbial activity screening revealed that compounds 5b,
5e, 6b, 6c, and 6e displayed better microbial inhibition. The
binding mode of the synthesized compounds with protein
active site was predicted using molecular docking. Com-
pounds 5d, 5h, and 6j showed promising dock score values
with more number of hydrogen bonding interactions. These
in silico findings are well supported by results of anti-
oxidant activity.
Supplementary materials
1
Spectral data of compounds 5a–j and 6a–j; H NMR, 13C
NMR and mass spectra of representative synthesized deri-
vatives are provided in supplementary materials.
Acknowledgements The authors are grateful to Department of
Chemistry, Osmania University for providing laboratory facilities,
CFRD, and spectral analysis. One of the authors, K.R. is thankful to
UGC-New Delhi, India, for granting Senior Research Fellowship.
Compliance with ethical standards
Molecular docking
Conflict of interest The authors declare that they have no competing
interests.
Molecular docking was performed on crystal structure of
tyrosinase from B. megaterium (PDB code: 3NM8) and
imported into MVD.4.0 (Kalgutkar et al. 1998). All water
molecules and co-factors were deleted. Then they were
exported as mol2 files and docked by using MVD. We used
the template docking available in MVD and evaluated
MolDock score, Rerank score, and protein–ligand interac-
tion score from MolDock and MolDock [GRID] options.
Ascorbic acid was selected as reference compound for the
template. It was used the default settings, including a grid
resolution of 0.30 Å, the MolDock optimizer as a search
algorithm, and the number of runs was set to 10. A popu-
lation size of 50, maximum iteration of 2000, scaling factor
of 0.50, crossover rate of 0.90 was set. The maximum
number of poses to generate was increased to 10 from a
default value of 5.
References
Ashok D, Rangu K, Rao VH, Gundu S, Srilata B, Vijjulatha M (2016)
Microwave-assisted synthesis, molecular docking and anti-
microbial activity of novel 2-(3-aryl,1-phenyl-1H-pyrazol-4-yl)-
8H-pyrano[2,3-f]chromen-4-ones. Med Chem Res 25:501–514
Azoro C (2002) Antibacterial activity of crude aqueous of Azadrichta
indica on Salmonella typhi. World J Biotechnol 3:347–351
Bishnu J, Sunil L, Anuja S (2009) Antibacterial property of different
medicinal plants: Ocimum sanctum, Cinnamomum zeylanicum,
Xanthoxylum armatum and Origanum majorana. J Sci Eng
Technol 5:143–150
Boumendjel A (2003) Aurones: a subclass of flavones with promising
biological potential. Curr Med Chem 10:2621–2630
Burits M, Bucar F (2000) Antioxidant activity of Nigella sativa
essential oil. Phytother Res 14:323–328
Cheng H, Zhang L, Liu Y, Chen S, Cheng H, Lu X, Zheng Z, Zhou
GC (2010) Design, synthesis and discovery of 5-hydroxyaurone
derivatives as growth inhibitors against HUVEC and some cancer
cell lines. Eur J Med Chem 45:5950–5957
Conclusions
Chung KT, Thomasson WR, Wu-Yuan CD (1990) Growth inhibition
of selected food-borne bacteria, particularly Listeria mono-
cytogenes, by plant extracts. J Appl Bacteriol 69:498–503
Cuendet M, Hostettmann K, Potterat O, Dyatmiko W (1997) Iridoid
glucosides with free radical scavenging properties from Fagraea
blumei. Helv Chim Acta 80:1144–1152
Detsi A, Majdalani M, Kontogiorgis CA, Hadjipavlou-Litina D,
Kefalas P (2009) Natural and synthetic 2′-hydroxy-chalcones and
aurones. Bioorg Med Chem 17:8073–8085
In summary, we synthesized a new series of compounds
5a–j and 6a–j under conventional and microwave irradia-
tion methods. In microwave irradiation method, reactions
were completed in short reaction time, mild reaction con-
ditions, high yields and convenient operation. All the titled
compounds have been screened for antioxidant activity
using DPPH and H2O2 radical scavenging assays. The
compounds 5d, 5h, 6e, and 6j were most potent with DPPH
Gulcin I, Buyukokuroglu ME, Oktay M, Kufrevioglu OI (2003)
Antioxidant and analgesic activities of turpentine of Pinus nigra

Med Chem Res
Arn. subsp. pallsiana (Lamb.) Holmboe. J Ethnopharmacol
86:51–58
development of potent antileishmanial agents. Int J Med Chem
196921, doi:10.1155/2012/196921
Hangum-balkir Y, Mckenney ML (2012) Determination of antioxidant
activities of berries and Resveratrol. Green Chem Lett Rev
5:147–153
Janovska D, Kubikova K, Kokoska L (2003) Screening for anti-
microbial activity of some medicinal plants species of traditional
Chinese medicine. J Food Sci 21:107–110
Jung MJ, Chung HY, Kang SS, Choi JH, Bae KS, Choi JS (2003)
Antioxidant activity from the stem bark of Albizzia julibrissin.
Arch Pharm Res 6:458–462
Kalgutkar AS, Crews BC, Rowlinson SW, Garner C, Seibert K,
Marnett LJ (1998) Aspirin-like molecules that covalently inacti-
vate cyclooxygenase-2. Science 280:1268–1270
Ruch RJ, Cheng SJ, Klaunig JE (1989) Prevention of cytotoxicity and
inhibition of intercellular communication by antioxidant cate-
chins isolated from Chinese green tea. Carcinogenesis
10:1003–1008
Schoepfer J, Fretz H, Chaudhuri B, Muller L, Seeber E, Meijer L,
Lozach O, Vangrevelinghe E, Furet P (2002) Structure-based
design and synthesis of 2-benzylidene-benzofuran-3-ones as fla-
vopiridol mimics. J Med Chem 45:1741–1747
Shrestha S, Natarajan S, Park JH, Lee DY, Cho JG, Kim GS, Jeon YJ,
Yeon SW, Yang DC, Baek NI (2013) Potential neuroprotective
flavonoid-based inhibitors of CDK5/p25 from Rhus parviflora.
Bioorg Med Chem Lett 23:5150–5154
Kerboeuf D, Riou M, Guégnard F (2008) Flavonoids and related
compounds in parasitic disease control. Mini Rev Med Chem
8:116–28
Sim HM, Loh KY, Yeo WK, Lee CY, Go ML (2011) Aurones as
modulators of ABCG2 and ABCB1. Chem Med Chem
6:713–724
Kim IT, Park YM, Shin KM, Ha JH, Choi JW, Jung HJ, Park HJ, Lee
KT (2004) Anti-inflammatory and anti-nociceptive effects of the
extract from Kalopanax pictus, Pueraria thunbergiana and Rhus
verniciflua. J Ethnopharmacol 94:165–173
Song MY, Jeong GS, Kwon KB, Ka SO, Jang HY, Park JW, Kim YC,
Park BH (2010) Sulfuretin protects against cytokine-induced
beta-cell damage and prevents streptozotocin-induced diabetes.
Exp Mol Med 42:628–638
Ku CS, Mun SP (2008) Characterization of seed oils from fresh
Bokbunja (Rubus coreanus Miq.) and wine processing waste.
Bioresour Technol 99:2852–2856
Lee EH, Song DG, Lee JY, Pan CH, Um BH, Jung SH (2008) Inhi-
bitory effect of the compounds isolated from Rhus verniciflua on
aldose reductase and advanced glycation endproducts. Biol
Pharm Bull 31:1626–1630
Pare PW, Dmitrieva N, Mabry TJ (1991) Phytoalexin aurone induced
in Cephalocereus senilis liquid suspension culture. Phytochem-
istry 30:1133–1135
Park KY, Jung GO, Lee KT, Choi JW, Choi MY, Kim GT, Jung HJ,
Park HJ (2004) Antimutagenic activity of flavonoids from the
heartwood of Rhus verniciflua. J Ethnopharmacol 90:73–79
Politeo O, Jukic M, Milos M (2007) Chemical composition and
antioxidant capacity of free volatile aglycones from basil (Oci-
mum basilicum L.) compared with its essential oil. Food Chem
101:379–385
Sreenivas P (2011) Synthesis and antibacterial activity of some new
spiro[pyrano[2,3-f]chromene-2,10-cycloalkan]-4-ones and 10-
alkylspiro[pyrano[2,3-f]chromene-2,40-piperidin]-4-ones. Indian
J Chem Sect B 50B:1484–1490
Tepe B, Daferera D, Sokmen A, Sokmen M, Polissiou M (2005)
Antimicrobial and antioxidant activities of the essential oil and
various extracts of Salvia tomentosa Miller (Lamiaceae). Food
Chem 90:333–340
Turkoglu A, Duru ME, Mercan N, Kivrak I, Gezer K (2007) Anti-
oxidant and antimicrobial activities of laetiporus sulphurus (bull.)
Murrill. Food Chem 101:267–273
Venkateswarlu S, Panchagnula GK, Gottumukkala AL, Subbaraju GV
(2007) Synthesis, structural revision, and biological activities of
4′-chloroaurone, a metabolite of marine brown alga Spatoglossum
variabile. Tetrahedron 63:6909–6914
Yin H, Xu L, Porter NA (2011) Free radical lipid peroxidation:
mechanisms and analysis. Chem Rev 111:5944–5972
Roussaki M, Lima SC, Kypreou AM, Kefalas P, Cordeiro da Silva A,
Detsi A (2012) Aurones: a promising heterocyclic scaffold for the