An Efficient, Eco-Friendly Synthesis of Pyran Annulated Indole Analogs under Conventional Heating and Microwave Irradiation, and Their Anticancer and Antioxidant Activity

Article abstract of DOI:10.1134/S1070363218100262

A rapid, facile, green, eco-friendly, cost effective, and efficient method for the synthesis of pyran annulated indole analogs via one-pot, three components reaction is developed. According to the developed method 2,5-disubstituted-1H-indol-3-carboxaldehyde, malononitrile and various phenols react under MW assisted solvent-free conditions. These compounds can be also prepared under a conventional method that is characterized by some disadvantages in comparison with the above approach. Structures of products are confirmed by FT-IR, ¹H and ¹³C NMR, and mass spectral data. The in vitro antioxidant and cytotoxic activities of the products are evaluated against three tumor cell lines and discussed in terms of structure―activity analysis. Among the screened compounds 3d, 4a, 4b, 5a, and 5b exhibit excellent antioxidant activity. Compounds 4b, 5a, and 5b demonstrate strong cytotoxic activity.

Full text of DOI:10.1134/S1070363218100262

ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 10, pp. 2190–2196. © Pleiades Publishing, Ltd., 2018.
An Efficient, Eco-Friendly Synthesis
of Pyran Annulated Indole Analogs
under Conventional Heating and Microwave Irradiation,
and Their Anticancer and Antioxidant Activity1
A. S. Rathoda* and J. S. Biradara
a Central Research Laboratory, Department of Chemistry, Gulbarga University, Kalaburagi, Karnataka, 585106 India
*e-mail: anilrathod086@gmail.com
Received August 10, 2018
Abstract―A rapid, facile, green, eco-friendly, cost effective, and efficient method for the synthesis of pyran
annulated indole analogs via one-pot, three components reaction is developed. According to the developed
method 2,5-disubstituted-1H-indol-3-carboxaldehyde, malononitrile and various phenols react under MW
assisted solvent-free conditions. These compounds can be also prepared under a conventional method that is
characterized by some disadvantages in comparison with the above approach. Structures of products are
confirmed by FT-IR, 1H and 13C NMR, and mass spectral data. The in vitro antioxidant and cytotoxic activities
of the products are evaluated against three tumor cell lines and discussed in terms of structure―activity
analysis. Among the screened compounds 3d, 4a, 4b, 5a, and 5b exhibit excellent antioxidant activity.
Compounds 4b, 5a, and 5b demonstrate strong cytotoxic activity.
Keywords: indole, phenols, pyran, MW-irradiation, green synthesis, catalyst, anticancer and antioxidant
activities
DOI: 10.1134/S1070363218100262
INTRODUCTION
Indole and its analogs comprise a significant class
of therapeutic agents including anticancer [3, 5],
antioxidant [9, 10], antirheumatoidal, and anti-HIV
[11, 12]. Many indole analogs are considered to be
potent scavengers of free radicals [3, 4, 9, 10].
Cancer and atherosclerosis are two major causes of
death promoted by the salient “free radical” impact.
Development of new drugs against cancer continues to
be the main objective for fundamental research [1–3].
MW-Assisted organic synthesis in many instances
is an ecologically friendly solvent free and catalyst free
method that can influence upon chemo-, regio-, and
stereo-selectivity [8].
Probably, endogenous free radical reactions, like
those initiated by ionizing radiation, can lead to tumors
formation. One of correlations between reactive oxygen
species (ROS) and cancer is the increased death rates
from leukemia and malignant neoplasia of breast,
ovaries and rectum induced by a greater impact of lipid
peroxidation [1, 4, 5]. ROS may cause initiation of
lipid peroxidation, direct inhibition of mitochondrial
respiratory enzymes, deactivation of glyceraldehyde-3-
phosphate dehydrogenase, inhibition of membrane
sodium/potassium ATPase activity, deactivation of
membrane sodium channel and other oxidative
alteration of proteins. All these toxic effects are likely
to play a crucial role in pathophysiology of shock,
inflammation and ischemia-reperfusion injury [6–8].
As an extension of our interest in green chemistry
of bioactive indoles [1, 3, 4, 9–11], we present herein a
rapid and ecofriendly synthesis of pyran annulated 2,5-
disubstituted indole analogs by conventional method
and MW irradiation (with and without a catalyst and
neat) under solvent-free conditions (Scheme 1). The
synthesized compounds were evaluated for cytotoxic
and antioxidant activities.
RESULTS AND DISCUSSION
In the present study synthetic approach to indole
analogs was carried out under two different reaction
conditions, conventional method and solvent-free MW-
1 The text was submitted by the authors in English.
2190

AN EFFICIENT, ECO-FRIENDLY SYNTHESIS OF PYRAN ANNULATED INDOLE ANALOGS
2191
Scheme 1. Synthetic approach to indole analogs.
OH
NH
R
R1
CN
O
NH2
3a−3d
OH
R
N
NH
R
CHO
R1
CN
CN
R1
Reflux, MW
Neat, catalyst
H2C
+
CN
N
H
O
NH2
1a−1d
2
N
4a−4d
OH
O
NH
R
R1
O
CN
O
O
NH2
O
5a−5d
R = Cl, R1 = Ph (a), R = CH3, R1 = Ph (b), R = H, R1 = Ph (c), R = R1 = H (d).
irradiation (Scheme 1). According to the first approach
heating of the mixture of equivalent amounts of 2,5-
conditions (without a solvent or a catalyst). However,
this approach suffered from very low yields and long
reaction time, sometimes no reaction occurred.
Catalysis by KNaC4H4O6·4H2O (10 mol %) under
solvent-free conditions led to formation of the products
3a–3d, 4a–4d, 5a–5d with high yields (80–94%).
Structures of the synthesized compounds were
elucidated from IR, 1H and 13C NMR, and mass
spectra.
disubstituted-1H-indole-3-carboxaldehyde
(1a–1d)
with malononitrile (2) and α-naphthol, 8-hydroxy-
quinoline, and 4-hydroxycoumarin gave low yields (25–
35%) of the products. Among other disadvantages of
the method were use of a solvent and long reaction
time.
Under solvent-free conditions and MW-irradiation
the synthesis led to formation of the products with 80–
94% yields (Table 1). In an attempt to improve the
reaction yield the process was carried out under neat
Biological evaluation. Melatonin and other indole
analogs may reduce incidence and growth of tumors
probably due to their antioxidant activity [12, 13]. In
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RATHOD, BIRADAR
Table 1. Synthesis of novel indole derivatives data
Conventional
MW-irradiation at 125–150°C
neat + KNaC4H4O6·4H2O
Comp.
no
reflux–EtOH
neat
mp, °C
time, h yield, % time, min power, W
yield, %
50
time, min
power, W
350
yield, %
3a
3b
3c
3d
4a
4b
4c
4d
5a
5b
5c
5d
12
12
10
10
12
12
09
09
12
12
09
09
35
30
25
25
35
32
35
30
35
31
25
25
10
10
8
450
450
450
450
450
450
450
450
450
450
450
450
5
5
6
6
5
5
5
5
6
6
6
6
94
92
90
90
92
90
89
88
94
92
88
88
248–249
258–259
249–250
209–210
259–260
250–251
218–219
220–221
225–226
238–239
186–187
210–211
42
350
50
350
a
8
–
350
10
10
9
50
45
42
350
350
350
a
9
–
350
10
10
9
40
40
350
350
a
–
350
a
8
–
350
a (–) No reaction occurred.
the current study the antioxidant activity of 2,5-
disubstituted indole analogs was evaluated.
compounds 5b–5d were of moderate activity. The
compounds scavenged the DPPH radical in a
concentration dependent manner (Fig. 1).
Free radical scavenging activity (FRSA). Samples
were prepared at concentrations of 25, 50, 75, and
100 µg/mL. Butylated hydroxyanisole (BHA) and
ascorbic acid (AA) were used as standards. The
presence of different substituents at the position C5 of
indole allowed to compare the influence of these upon
scavenging activity. It is noteworthy that the
unsubstituted in position C5 compounds 3d, 4d
demonstrated the highest scavenging activity. Whereas
Total antioxidant capacity (TAC). Antioxidant
capacity is expressed as equivalents of ascorbic acid.
Some of the synthesized ring systems demonstrated
positive tendency towards TAC. According to the
earlier reports [4, 9, 10], indole derivatives exhibited
moderate to low activity. It was also observed that
chlorine and methyl group substituents at the position
C5 of the indole ring 4a, 4b, 5a, and 5b stimulated the
antioxidant capacity. In contrast unsubstituted
derivatives demonstrated lower activity (Fig. 2).
Inhibition, %
100
25
50
75 100
Ferric reducing antioxidant power activity
(FRAPA). The synthesized compounds reduced Fe+3
60
cations in
a
concentration dependent manner.
Butylated hydroxyanisole and ascorbic acid were used
as standards. Screening results indicated that all newly
synthesized indole analogs were active ferric reducing
antioxidant agents, with varying degree of potency.
Indol derivatives 4a, 4b demonstrated excellent ferric
reducing activity. The other analogues were of
moderate to high activity. Substituents Cl and CH3 at
C5 position of the indole ring supported high activity of
the products (Fig. 3).
20
3a 3b 3c 3d 4a 4b 4c 4d 5a 5b 5c 5d
Compounds
Fig 1. DPPH free radical scavenging activity; (BHA)
butylated hydroxyanisole and (AA) ascorbic acid.
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AN EFFICIENT, ECO-FRIENDLY SYNTHESIS OF PYRAN ANNULATED INDOLE ANALOGS
Absorbance at 700 nm, %
2193
Equivalent to AA, μg
100
25
50
75 100
100
25
75
50
100
60
20
60
20
3a 3b 3c 3d 4a 4b 4c 4d 5a 5b 5c 5d
3a 3b 3c 3d 4a 4b 4c 4d 5a 5b 5c 5d
Compounds
Compounds
Fig. 3. Influence of the synthesized compounds upon FRPA;
Fig. 2. Total antioxidant capacity; (AA) ascorbic acid.
(BHA) butylated hydroxyanisole and (AA) ascorbic acid.
In vitro cytotoxic studies. Preliminary evaluation of
antitumor cytotoxicity of the synthesized compounds
was studied against three different tumor cell lines,
A-549 (Lung carcinoma), HEp-2 (Laryngeal
carcinoma) and HeLa (Cervical carcinoma) by the
MTT assay with Doxorubicin as a positive reference
[3, 4] (Table 2). The compounds 5b demonstrated
effective cytotoxicity against all three cell lines.
Compound 4b exhibited high cytotoxic activity against
A-549 (IC50 22.61 µM) and HeLa (IC50 88.16 µM) but
not against HEp-2. In contrast, compounds 3a, 3b
demonstrated the lowest activity against HeLa (IC50
84.28, 83.04 µM), and compounds 3a, 3b, and 4b
failed to show any activity against cell lines A-549 and
HEp-2. The results clearly indicated indolyl–dihyd-
ropyrano–chromene 5a, 5b as
a system with
potentially strong cytotoxicity against all three cell
lines. Whereas, the compounds with Cl and CH3
Table 2. In vitro cytotoxicity of indol analoguesa
IC50, µM
Comp.
no.
A-549 (lung carcinoma)
HEp-2 (laryngeal carcinoma)
HeLa (cervical carcinoma)
3a
>100
71.02
>100
85.46
>100
22.61
51.29
45.06
>100
24.30
85.21
56.54
0.70
>100
>100
70.15
46.92
>100
>100
35.55
50.92
18.56
50.53
45.21
63.32
8.70
84.28
83.04
68.52
54.21
71.09
80.16
49.52
66.56
56.90
59.77
72.12
32.12
0.71
3b
3c
3d
4a
4b
4c
4d
5a
5b
5c
5d
Doxorubicin
a (>100) active but IC50 could not be calculated due to lesser % inhibition, (IC50) the compound concentration for which the growth of
treated cells from time “0” was only 50%.
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RATHOD, BIRADAR
substitution at C5 position of indole had some tendency
to initiate the activity.
molecular sieves (0.5–1.0 g). The mixture was
subjected to MW irradiation at moderate power (350–
450 W) for 5–6 min and introduced in an open borosil
glass vessel (to decrease internal pressure). This was
subjected to MW irradiation for 10 min at 125–150°C
followed by the corresponding manipulations developed
earlier [4].
EXPERIMENTAL
All chemicals used were purchased from Merck,
Himedia and SD fine chemicals and used as such.
Reaction progress was monitored by TLC (Merck
Silica gel 60 F245 plates). The spots were visualized by
UV light at 254 nm. Melting points were measured in
open capillary tubes and are uncorrected. IR spectra
After completion of the process (TLC), the reaction
mixture was poured into crushed ice. The crude
product was filtered off on a Buchner funnel and
purified by crystallization from hot ethanol.
were recorded on
a
Perkin Elmer FT-IR
spectrophotometer for KBr discs. H and 13C NMR
spectra were measured on a Bruker 400MHz, SAIF in
DMSO-d6 using TMS as an internal standard. LCMS
spectra were measured on a SHIMADZU, LCMS
2O1OA, Mass spectrometer. MW-Irradiation reactions
were carried out in a ONIDA 20STP21 800W
multimode microwave oven.
1
2-Amino-4-(5-chloro-2-phenyl-1H-indol-3-yl)-4H-
benzo[h]chromene-3-carbonitrile (3a). Light yellow
crystals, yield 96%, mp 248–249°C. IR spectrum, ν,
cm–1: 3450(NH), 3353(NH2), 3001(Ar-H), 2920 (CH),
1
2143 (CN), 1298(O), 710 (C–Cl). H NMR spectrum,
δ, ppm: 4.45 s (1H, CH), 7.29–7.82 m (14H, Ar-H),
9.98 s (2H, NH2), 12.60 s (1H, NH indole). 13C NMR
spectrum, δ, ppm: 112, 113, 120,123, 126, 129, 130,
134 (Ar-C), 150 (C–NH2). MS: m/z 447 [M]+ (27%),
449 [M + 2]+ (9%).
Synthesis of 2,5-disubstituted indole-3-carboxal-
dehydes (1a–1d). The precursors 2,5-disubstituted
indole-3-carboxaldehydes 1a–1d were synthesized by
the Vilsmeier–Haack formylation reaction of 2,5-di-
substituted indoles [1].
2-Amino-4-(5-methyl-2-phenyl-1H-indol-3-yl)-4H-
benzo[h]chromene-3-carbonitrile (3b). Yellowish-
green powder, yield 98%, mp 258–259°C. IR spectrum,
ν, cm–1: 3584 (NH), 3231 (NH2), 2941 (CH3), 2147
Synthesis of 3a–3d, 4a–4d, and 5a–5d.
A. Conventional method. A mixture of 2,5-di-
substituted indole-3-carboxaldehyde (0.01 mmol) with
malononitrile (0.01 mmol) and α-naphthol,
8-hydroxyquinoline, 4-hydroxycoumerin (0.01 mmol)
in ethanol (15 mL) was heated for certain time
intervals (Table 1).
1
(CN), 1320 (O). H NMR spectrum, δ, ppm: 2.43 s
(3H, CH3), 4.35 s (1H, CH), 7.10–8.04 m (14H, Ar-H),
9.95 s (2H, NH2), 12.30 s (1H, NH indole). 13C NMR
spectrum, δ, ppm: 21.54 (CH3), 71 (C–CN), 108, 112,
115, 116, 122, 124, 125, 129, 130, 131, 135, 149
(Ar-C), 154 (C–NH2). MS: m/z 427 [M]+ (13%).
B. MW-assisted synthesis. (1). Neat reaction. A
mixture of 2,5-disubstituted indole-3-carboxaldehyde
(0.01 mmol) with malononitrile(0.01mmol) and
α-naphthol, 8-hydroxyquinoline, 4-hydroxycoumerin
(0.01 mmol) was mixed with finely powdered 5 Å
molecular sieves (0.5–1.0 g). The mixture was
subjected to MW irradiation at moderate power (350–
450 W) for 8–10 min and loaded into an open borosil
glass vessel (to decrease internal pressure). This was
subjected to MW irradiation for 10 min at 125–150°C
followed by the corresponding manipulations as
reported [4].
2-Amino-4-(2-phenyl-1H-indol-3-yl)-4H-benzo-
[h]chromene-3-carbonitrile (3c). Light brownish
powder, yield 90%, mp 249–250°C. IR spectrum, ν,
cm–1: 3351 (NH), 3323 (NH2), 2900 (CH), 2183 (CN),
1208 (O). 1H NMR spectrum, δ, ppm: 4.01 s (1H, CH),
6.29–7.10 m (15H, Ar-H), 9.80 s (2H, NH2), 12.20 s
(1H, NH indole). MS: m/z 413 [M]+.
2-Amino-4-(1H-indol-3-yl)-4H-benzo[h]chromene-
3-carbonitrile (3d). Dark yellow powder, yield 95%,
mp 209–210°C. IR spectrum, ν, cm–1: 3411(NH), 3393
1
(NH2), 2890 (CH), 2133 (CN), 1308 (O). H NMR
spectrum, δ, ppm: 4.82 s (1H, CH), 7.29–8.10 m (15H,
Ar-H), 9.70 s (2H, NH2), 11.80 s (1H, NH indole).
MS: m/z 337 [M]+.
(2) Neat with KNaC4H4O6·4H2O. A mixture of 2,5-
disubstituted indole-3-carboxaldehyde (0.01 mmol)
with malononitrile (0.01 mmol) and α-naphthol,
8-hydroxyquinoline, 4-hydroxycoumerin (0.01 mmol)
was combined with powdered KNaC4H4O6·4H2O
(10 mol %), and mixed with finely powdered 5 Å
2-Amino-4-(5-chloro-2-phenyl-1H-indol-3-yl)-4H-
pyrano[3,2-h]quinoline-3-carbonitrile (4a). Gray
powder, yield 97%, mp 259–260°C. IR spectrum, ν,
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AN EFFICIENT, ECO-FRIENDLY SYNTHESIS OF PYRAN ANNULATED INDOLE ANALOGS
2195
1
cm–1: 3431 (NH), 3367 (NH2), 2880 (CH), 2142 (CN),
1437 (C=N), 1318 (O), 711 (C–Cl). 1H NMR
spectrum, δ, ppm: 4.71 s (1H, CH), 7.30–8.20 m (13H,
Ar-H), 9.96 s (2H, NH2), 12.60 s (1H, NH indole). 13C
NMR spectrum, δ, ppm: 112, 113, 120,123, 126, 129,
130, 134 (Ar-C), 150 (C–NH2). MS: m/z 448 [M]+
(20%), 450[M + 2]+ (7%).
1318 (O). H NMR spectrum, δ, ppm: 2.45 s (3H,
CH3), 4.54 s (1H, CH), 7.18–7.95 m (12H, Ar-H), 8.22
s (2H, NH2), 11.71 s (1H, NH indole). 13C NMR
spectrum, δ, ppm: 21.29 (CH3), 111, 113, 120, 125,
126, 128, 129, 131, 134 (Ar-C), 148 (C–NH2), 185.39
(C=O). MS: m/z 445 [M]+ (29%).
3-Amino-5-oxo-1-(2-phenyl-1H-indol-3-yl)-1,5-
dihydropyrano[2,3-c]chromene-2-carbonitrile (5c).
Yellow brown powder, yield 88%, mp 186–187°C. IR
spectrum, ν, cm–1: 3422 (NH), 3352 (NH2), 2900 (CH),
2150 (CN), 1650 (C=O), 1350 (O). 1H NMR spectrum,
δ, ppm: 4.81 s (1H, CH), 7.01–8.20 m (13H, Ar-H),
9.06 s (2H, NH2), 11.00 s (1H, NH indole). MS: m/z
431 [M]+.
2-Amino-4-(5-methyl-2-phenyl-1H-indol-3-yl)-4H-
pyrano[3,2-h]quinoline-3-carbonitrile (4b). Light
greenish powder, yield 95%, mp 250–251°C. IR
spectrum, ν, cm–1: 3450 (NH), 3332 (NH2), 2878–2961
1
(CH3), 2143 (CN), 1437 (C=N), 1318 (O). H NMR
spectrum, δ, ppm: 2.43 s (3H, CH3), 4.42 s (1H, CH),
7.11–8.04 m (13H, Ar-H), 9.95 s (2H, NH2), 12.36 s
(1H, NH indole). 13C NMR spectrum, δ, ppm: 21.30
(CH3), 111, 113, 120, 125, 126, 128,129, 131, 134
(Ar-C), 149 (C–NH2). MS: m/z 428 [M]+ (10%).
3-Amino-1-(1H-indol-3-yl)-5-oxo-1,5-dihydro-
pyrano[2,3-c]chromene-2-carbonitrile (5d). Dark
brown powder, yield 88%, mp 210–211°C. IR
spectrum, ν, cm–1: 3322 (NH), 3252 (NH2), 2982 (CH),
2180 (CN), 1680 (C=O), 1310 (O). 1H NMR spectrum,
δ, ppm: 4.01 s (1H, CH), 7.20–8.00 m (9H, Ar-H),
9.01 s (2H, NH2), 11.10 s (1H, NH indole). MS: m/z
355 [M]+.
2-Amino-4-(2-phenyl-1H-indol-3-yl)-4H-pyrano-
[3,2-h]quinoline-3-carbonitrile (4c). Greenish powder,
yield 89%, mp 218–219°C. IR spectrum, ν, cm–1: 3400
(NH), 3337 (NH2), 2980 (CH), 2170 (CN), 1450
1
(C=N), 1300 (O). H NMR spectrum, δ ppm: 4.12 s
(1H, CH), 7.50–8.10 m (14H, Ar-H), 9.86 s (2H, NH2),
11.90 s (1H, NH indole). MS: m/z 414 [M]+.
Biological activities. Free radical DPPH scavenging
activity. The synthesized compounds were screened for
in-vitro DPPH free radical scavenging activity
according to the developed earlier method [4, 9, 10].
2-Amino-4-(1H-indol-3-yl)-4H-pyrano[3,2-h]-
quinoline-3-carbonitrile (4d). Light greenish powder,
yield 88%, mp 220–221°C. IR spectrum, ν, cm–1: 3350
(NH), 3302 (NH21), 2908 (CH), 2163 (CN), 1400
(C=N), 1320 (O). H NMR spectrum, δ, ppm: 4.32 s
(1H, CH), 7.01–8.00 m (10H, Ar-H), 9.05 s (2H, NH2),
11.36 s (1H, NH indole). MS: m/z 338 [M]+.
Total antioxidant capacity. The total antioxidant
capacity of the synthesized compounds was evaluated
by the phosphomolybdenum method as described
[4, 9, 10].
Ferric reducing antioxidant power activity. The
total reducing power of the synthesized compounds
was determined according to the earlier developed
method [4, 9, 10].
3-Amino-1-(5-chloro-2-phenyl-1H-indol-3-yl)-5-
oxo-1,5-dihydropyrano[2,3-c]chromene-2-carbo-
nitrile (5a). Light yellow powder, yield 94%, mp 225–
226°C. IR spectrum, ν, cm–1: 3435 (NH), 3410 (NH2),
2996 (Ar-H), 2913 (C-H), 2173 (CN), 1656 (C=O),
In vitro cytotoxic studies. A-549 (Lung carcinoma),
HEp-2 (Laryngeal carcinoma) and HeLa (Cervical
carcinoma) cell lines were procured from ATCC, stock
cells were cultured in DMEM supplemented with 10%
inactivated Fetal Bovine Serum (FBS), penicillin
(100 IU/mL), streptomycin (100 µg/mL) in a
humidified atmosphere of 5% CO2 at 37°C until
confluent. The cells were dissociated in TPVG solution
(0.2% trypsin, 0.02% EDTA, 0.05% glucose in PBS),
their viability was checked, and then those were
centrifuged. 50,000 Cells/well of Jurkat was seeded in
a 96 well plate and incubated for 24 h at 37°C, and
incubated (5%CO2) as reported [3, 4].
1
1312 (O), 702 (C–Cl). H NMR spectrum, δ, ppm:
3.62 s (1H, CH), 7.30–8.19 m (12H, Ar-H), 9.95 s (2H,
NH2), 12.63 s (1H, NH indole). 13C NMR, spectrum, δ
ppm: 74 (C–CN), 107, 112, 113, 114, 115, 116, 120,
123, 121, 126, 129, 130, 134, 135, 149, 150 (Ar-C),
154 (C–NH2), 185.52 (C=O). MS: m/z 465 [M]+
(10%), 467 [M + 2]+ (3%).
3-Amino-1-(5-methyl-2-phenyl-1H-indol-3-yl)-5-
oxo-1,5-dihydropyrano[2,3-c]chromene-2-carbo-
nitrile (5b). Dark brown powder, yield 92%, mp 238–
239°C. IR spectrum, ν, cm–1: 3434 (NH), 3402 (NH2),
2998 (Ar-H), 2913 (CH), 2144 (CN), 1658 (C=O),
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RATHOD, BIRADAR
CONCLUSIONS
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We have used efficient and ecologically safe
methods for the synthesis of pyran annulated indole
derivatives using two different reaction conditions.
The MW-irradiation method has some advantages such
as operational simplicity, neutral and clean reaction
conditions, high yields, easy work-up. The synthesized
compounds demonstrated moderate to good in vitro
cytotoxic activity against A-549 (Lung carcinoma),
HEp-2 (Laryngeal carcinoma) and HeLa (Cervical
carcinoma). Compounds 4b and 5b exhibited potent
growth inhibitory activity. Compounds 3d, 4a, 4b, 5a,
5b exhibit excellent antioxidant activity.
ACKNOWLEDGMENTS
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One of the authors, A.S. Rathod is thankful to UGC-
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226/2009 (BSR) dated November 19, 2014, New Delhi
(India) for financial support, Dr. S. Yogish, Director,
Founder, Skanda Life Sciences and Research Centre,
Bengaluru for Anti-Cancer activities, Director, SAIF,
Punjab, for providing IR, 1H NMR, 13CNMR and Mass
Spectra data.
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CONFLICT OF INTERESTS
No conflict of interests was declared by the authors.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 10 2018