Synthesis, antioxidant and α -amylase inhibition activity of naphthalene-containing 2,4,5-trisubstituted imidazole derivatives

Article abstract of DOI:10.1007/s12039-019-1639-0

Abstract: A series of naphthalene ring containing 2,4,5-trisubstituted imidazole derivatives (2a–2l) were synthesized using one-pot multicomponent reaction. The reactions were carried out using naphthaldehyde and substituted benzil in the presence of ammo

Full text of DOI:10.1007/s12039-019-1639-0

J. Chem. Sci.
(2019) 131:62
© Indian Academy of Sciences
https://doi.org/10.1007/s12039-019-1639-0
REGULAR ARTICLE
Synthesis, antioxidant and α-amylase inhibition activity
of naphthalene-containing 2,4,5-trisubstituted imidazole
derivatives
B SOMASHEKARAa,c, B THIPPESWAMYb,c and G R VIJAYAKUMARc,∗
aDepartment of Chemistry, Smt. Indira Gandhi Government First Grade Women’s College, Sagar, Karnataka
577 401, India
bDepartment of Chemistry, Government First Grade Science College, Chitradurga, Karnataka 577 501, India
cDepartment of Chemistry, University College of Science, Tumkur University, Tumkur, Karnataka 572 103,
India
E-mail: vijaykumargr18@gmail.com
MS received 8 February 2019; revised 26 April 2019; accepted 3 May 2019
Abstract. A series of naphthalene ring containing 2,4,5-trisubstituted imidazole derivatives (2a–2l) were
synthesized using one-pot multicomponent reaction. The reactions were carried out using naphthaldehyde and
substituted benzil in the presence of ammonium acetate in acetic acid media. All newly synthesized imidazole
derivatives were characterized by FT-IR, 1H NMR, 13C NMR and mass spectral analysis. Newly synthesized
imidazole derivatives were screened for their in-vitro antioxidant activity by DPPH free radical scavenging assay
method and α-amylase inhibition activity by DNS method. All the compounds showed excellent α-amylase
activity at 10, 50 and 100 μg/mL and compounds 2d, 2g, 2k exhibited good antioxidant activity.
Keywords. 2,4,5-trisubstituted imidazole; one-pot multicomponent reaction; antioxidant activity; α-amylase
activity.
1. Introduction
radicalsaredangerstothehumanbodyandwhichcauses
oxidative stress. Oxidative stress leads to cancer,12–14
In the recent years, imidazole derivatives received heart diseases,15 osteoarthritis,16,17 stroke,18 respiratory
significant attention due to their biological and phar- diseases,19 immune deficiency,20 Parkinson’s disease,21
macological importance. Many imidazole derivatives emphysema22 and other inflammatory or ischemic con-
are occurring in natural compounds extracted from ditions. Therefore, there is an urgent need to design and
herbs. The substituted imidazole derivatives have a wide develop a highly active antioxidant compounds.
α
range of applications in pharmaceutical industries as an
-Amylase inhibitors are the targets for the many
antioxidant,1 anticancer,2 anti-inflammatory,3 antimi- researchers in drug-design for the development of a
crobial,4,5 antihypertension activity.6 On the other hand, new class of compounds for the treatment of hyperli-
the trisubstituted imidazole moieties are promising can- paemia, diabetes and obesity. Enzyme inhibitors are the
didates for α-amylase inhibition,7 C17, 20-lyase inhibi- potential target in many diseases which control many
tion,8 glucosidase inhibition9,10 and kinase inhibition.11 important biochemical reactions. -Amylase inhibitors
α
The antioxidant property of the compound is very are the substances which control carbohydrate diges-
important to protect damage against free radicals that tion and monosaccharide absorption. In this aspect,
α
are produced in our body as a result of a biochemical
-amylase inhibitors are particularly important in main-
reaction. Free radicals are generated due to internal fac- taining a constant glucose level in the blood by delaying
α
tors such as inflammation and external factors such as the breakdown of starch. Many available -amylase
environmental pollution, and UV exposure. These free inhibitors are the microbial origin and their usage
*
For correspondence
Electronic supplementary material: The online version of this article (https://doi.org/10.1007/s12039-019-1639-0) contains
supplementary material, which is available to authorized users.
0123456789().: V,-vol

62 Page 2 of 7
J. Chem. Sci.
(2019) 131:62
α
has been limited due to their side effects. Various - compound precipitated was filtered and dried. All the crude
amylase inhibitors are synthesized23,24 and screened
for their inhibitory activity which include iminosugars,
thiosugars, disaccharides, carbosugars and non-sugar
products were purified by column chromatography except 2a,
2b, 2c, 2d and 2h, which purified by recrystallization using
ethanol.
α
derivatives. The -amylase inhibitors with a high degree
2.2a 4,5-bis(3-methoxylphenyl)-2-(naphthalen-2-yl)-
1H-imidazole (2a): Pale yellow solid; M.p. 184−186 ◦C;
νmax
H) 1607.38 (C=C), 1585.20 (C=N); H NMR (500 MHz,
DMSO − d6) δ (ppm): 3.70 (s, 3H, -OCH3), 3.77 (s, 3H,
-OCH3), 6.83 (m, 1H, ArH), 6.98 (dd, J = 8.3 Hz, 1H,
ArH), 7.12 (m, 2H, ArH), 7.19 (d, J = 7.6 Hz, 2H, ArH),
7.25 (t, J = 7.9 Hz, 1H, ArH), 7.38 (t, J = 7.9 Hz, 1H,
ArH), 7.55 (dd, J = 15.6 Hz, 6.5 Hz, 2H, ArH), 7.96 (q,
of potency and specificity are still needed for the explo-
ration of a new class of inhibitors. In this respect, several
naphthalene incorporated heterocyclic compounds were
synthesized and tested for their biological activities such
as anticonvulsant,25,26 antimicrobial,27–29 antioxidant30
and anticancer activity.31,32 In view of the above obser-
vation, in our study we have synthesized naphthalene
incorporated 2,4,5-trisubstituted imidazole derivatives
α
FT-IR (KBr, cm−1
)
: 3410.19 (N-H), 3051.80 (Ar-
1
and have screened for their antioxidant and -amylase J = 7.6 Hz, 2H, ArH), 8.02 (d, J = 8.3 Hz, 1H, ArH), 8.26
(dd, J = 9.0 Hz, 1.4 Hz, 1H, ArH), 8.61 (s, 1H, ArH), 12.85
inhibition activity.
(s, 1H, NH), 13C NMR (400 MHz, DMSO − d6) δ (ppm):
49.9, 50.2, 107.3, 107.7, 108.4, 109.0, 114.7, 115.9, 18.6,
118.8, 121.4, 121.7, 122.8, 122.9, 123.1, 123.3, 123.6, 124.2,
2. Experimental
124.8, 127.3, 127.8, 128.0, 131.5, 132.4, 140.4, 154.1, 154.3;
MS (m/z): Calcd.406.16, found 407.17 [M+1].
2.1 Materials and methods
2.2b 4,5-bis(3-methoxylphenyl)-2-(naphthalen-1-yl)-
Chemicals used in the present work were purchased from
1H-imidazole (2b): Off white solid; M.p.: 185−186 ◦C;
Sigma-Aldrich (India), Merck (Germany) and S. D. Fine
FT-IR (KBr, cm−1
)
νmax
: 3418.18 (N-H), 3049.80 (Ar-
Chemicals (India). All the laboratory grade solvents used
were distilled before use. Melting points were determined
by an open capillary method and were uncorrected. The IR
spectra of the compounds (KBr pellet method) were recorded
1
H), 1606.41 (C=C), 1579.41 (C=N); H NMR (500 MHz,
CDCl3) δ (ppm):3.77(s, 6H, -OCH3), 6.83(dd, J = 8.3 Hz,
2.1 Hz,2H, ArH), 6.90 (dd, J = 8.3 Hz, 2.1 Hz, 1H, ArH),
7.06(s, 1H,ArH), 7.11 (d, J = 7.6 Hz, 1H, ArH), 7.23 (d,
J = 8.3 Hz, 1H, ArH), 7.34 (q, J = 8.7 Hz, 3H, ArH), 7.56
(m, 2H, ArH), 7.78 (dd, J = 6.9 Hz, 1.4 Hz, 1H, ArH), 7.92
(m, 2H, ArH), 8.82 (d, J = 8.3 Hz, 1H, ArH), 9.33 (s, 1H,
NH); 13C NMR (400 MHz, DMSO−d6), δ (ppm): 49.9, 50.1,
107.1, 107.9, 108.5, 108.8, 114.8, 115.7, 120.3, 121.2, 121.6,
121.7, 121.8, 122.5, 122.9, 123.3, 124.0, 124.3, 124.7, 125.4,
127.2, 128.7, 131.7, 132.1, 140.5, 154.2, 154.3; MS (m/z):
Calcd.406.16, found 407.03 [M+1].
1
on a JASCO FT/IR-4600 spectrophotometer. H NMR and
13C NMR spectra were recorded by using JEOL (500 MHz)
NMR spectrometer and Agilent (400 MHz) NMR spectrom-
eter respectively. The compounds were dissolved in either
DMSO−d6 or CDCl3 for recording the spectra in the presence
of TMS as an internal standard. Chemical shift values were
presented in δ (ppm) scale. The mass spectra were recorded
on a Agilent mass spectrometer instrument. The completion
of the reactions was checked by thin layer chromatography
(TLC) on silica gel coated aluminum sheets (silica gel 60
F254). The compounds name was given as per chem draw
software. Antioxidant activity was carried out by DPPH free
2.2c 4,5-bis(4-methylphenyl)-2-(naphthalen-1-yl)-
1H-imidazole (2c): Off white solid; M.p.: 280−284 ◦C;
νmax
FT-IR (KBr, cm−1
)
: 3391.21 (N-H), 3063.37 (Ar-
α
radical scavenging assay method. -Amylase inhibition activ-
1
H), 1614.13 (C=C), 1590.02 (C=N); H NMR (500 MHz,
CDCl3) δ (ppm): 2.36 (s, 3H, −CH3), 2.40 (S,3H, −CH3),
7.15 (d, J = 8.3 Hz, 2H, ArH), 7.22 (d, J = 7.6 Hz, 2H,
ArH), 7.42 (d, J = 7.6 Hz, 2H,ArH), 7.56 (m, 3H, ArH),
7.66 (d, J = 8.3 Hz, 2H, ArH), 7.77 (m, 1H, ArH), 7.91 (m,
2H, ArH), 8.84 (d, J = 8.3 Hz, 1H,ArH), 9.22 (s, 1H, NH);
13C NMR (400 MHz, DMSO − d6), δ (ppm): 21.2, 125.6,
126.5, 127.0, 127.5, 128.0, 128.5, 128.6, 129.6, 130.7, 133.
0, 134.0, 135.9, 137.3, 145.6; MS (m/z): Calcd.374.17, found
373.17 [M-1].
ity by DNS method. The chemicals used for antioxidant and
α
-amylase inhibition study was purchased from Hi-Media
(Mumbai)-India. Absorbance was recorded using Systronics-
169 Visible Spectrophotometer.
2.2 General procedure for the synthesis naphthalene
incorporated 2,4,5-trisubstituted imidazoles (2a-2l)
A mixture of naphthaldehyde (10 mmol), substituted benzil
(10 mmol) and ammonium acetate (50 mmol) were dissolved
in acetic acid in two necked 100 mL round bottom flask. The 2.2d 4,5-bis(4-methylphenyl)-2-(naphthalen-2-yl)-
reaction mixture was refluxed for 12–14 h. The completion 1H-imidazole (2d): Off white solid; M.p. 246−248 ◦C;
of reaction was monitored by TLC using petroleum ether and FT-IR (KBr, cm−1
)
max: 3418.21 (N-H), 3051.80 (Ar-H),
ν
1
ethyl acetate (3:1) as eluent. After completion of the reac- 1614.13 (C = C), 1589.06 (C = C); H NMR (500 MHz,
tion, the mixture was poured into ice cold water. The solid DMSO − d6) δ (ppm): 2.30 (s,3H, −CH3), 2.36 (s, 3H,

J. Chem. Sci.
(2019) 131:62
Page 3 of 7
62
−CH3), 7.13 (d, J = 7.6 Hz, 2H, ArH), 7.26 (d, J = 8.3 Hz,
J = 8.3 Hz, 1H, ArH), 7.99 (t, J = 6.9 Hz, 2H, ArH), 12.60
2H, ArH), 7.45 (dd, J = 27.2, 7.9 Hz, 4H, ArH), 7.55 (m, (s,1H, NH); MS (m/z):Calcd.406.16, found 407.14 [M+1].
2H, ArH), 7.95 (dd, J = 13.4 Hz, 7.9 Hz, 2H, ArH), 8.00
(d, J = 8.3 Hz, 1H, ArH), 8.24 (dd, J = 8.6 Hz,1.7 Hz, 1H,
2.2i 4-(4-chlorophenyl)-2-(napthalen-1-yl)-5-phenyl-
ArH), 8.60 (s, 1H, ArH), 12.74 (s, 1H, NH); 13C NMR (400
1H-imidazole ( 2i): Off white solid; M.p. 255−257 ◦C;
MHz, DMSO−d6), δ (ppm): 15.9, 118.5, 118.6, 121.3, 121.7,
FT-IR (KBr, cm−1
)
max: 3418.21 (N-H), 3049.87 (Ar-H),
ν
122.7, 122.9, 123.1, 123.2, 124.0, 127.7, 128.0, 131.4, 141.2;
1
1599.66 (C=C), 1583.27 (C=N), 745.35 (C-Cl); H NMR
(500 MHz, DMSO − d6) δ (ppm): 7.39 (t, J = 7.2 Hz,
1H, ArH), 7.41 (d, J = 7.6 Hz, 2H, ArH) ,7.49 (m,2H, ArH),
7.57 (d, J = 6.9 Hz, 2H, ArH),7.63 (m,5H, ArH), 7.96 (d,
J = 7.6 Hz, 1H, ArH), 8.01 (d, J = 7.6 Hz, 2H, ArH), 9.14
(d, J= 8.3 Hz, 1H, ArH), 12.85 (s,1H,NH); 13C NMR (400
MHz, DMSO − d6) δ (ppm): 120.3, 121.2, 121.5, 121.8,
122.4, 123.0, 123.3, 123.4, 123.5, 123.5, 123.7, 123.8, 124.1,
125.0, 125.4, 125.8, 126.0, 127.2, 128.7, 129.2, 130.1, 130.9,
132.7, 140.8, 140.9; MS (m/z): Calcd.380.10, found 381.14
[M+1].
MS (m/z): Calcd. 374.17, found 375.05 [M+1].
2.2e 4,5-bis(4-bromophenyl)-2-(naphthalen-1-yl)-1H
-imidazole (2e): Yellow solid; M.p.: 205 − 207 ◦C; FT-IR
(KBr, cm−1
)
max: 3417.28 (N-H), 1600.63 (C=C), 1584.24
ν
(C=N), 832; 1H NMR (500 MHz, CDCl3) δ (ppm): 6.55 (m,
2H, ArH), 6.64 (d, J = 1.8 Hz, 2H, ArH), 7.56 (m, 4H, ArH),
7.64 (m, 2H, ArH), 7.6 (d, J = 3.4 Hz, 2H, ArH), 7.78 (d,
J = 7.6 Hz, 2H, ArH), 8.7 (d,J = 8.3 Hz, 1H, ArH), 9.61
(s, 1H, NH); 13C NMR (400 MHz, DMSO − d6) δ (ppm):
121.2, 121.8, 121.9, 124.3, 125.3, 126.4, 126.7, 126.8, 127.6;
MS (m/z): Calcd.501.96, found 500.98 [M-1].
2.2j 4-(4-chlorophenyl)-2-(napthalen-2-yl)-5-phenyl-
1H-imidazole (2j): Pale brown solid; M.p. 222−224 ◦C;
FT-IR (KBr, cm−1
)
max: 3442.31 (N-H), 3056.62 (Ar-H),
ν
2.2f 2-(naphthalen-1-yl)-4,5-diphenyl-1H-imidazole
(2f): Pale yellow solid; M.p.: 262−263 ◦C; FT-IR (KBr,
νmax
1580.38 (C=N), 753.06 (C-Cl);1H NMR (500 MHz, DMSO−
d6) δ (ppm): 7.40 (m, 4H, ArH), 7.53 (m, 7H, ArH), 7.96 (q,
J = 7.6 Hz,2H, ArH), 8.02 (d, J = 9.0 Hz, 1H, ArH), 8,25
(dd, J = 8.6 Hz,1.7 Hz, 1H, ArH), 8.61 (s,1H, ArH), 12.92
(s, 1H, NH); 13C NMR (400 MHz, DMSO − d6) δ (ppm):
118.5, 118.8, 121.4, 121.8, 122.7, 122.8, 123.2, 123.3, 123.6,
127.8, 128.0, 140.8; MS (m/z):Calcd.380.10, found 380.98
[M+1].
cm−1
)
: 3417.24 (N-H), 3052.69 (Ar-H), 1600.63
(C=C), 1584.24 (C=N); 1H NMR (500 MHz, DMSO−d6) δ
(ppm): 7.25 (t, J = 7.6 Hz, 1H, ArH), 7.36 (m, 3H, ArH),
7.45 (t, J = 7.6 Hz, 2H, ArH), 7.57 (m, 2H, AH), 7.62(m, 5H,
AH), 7.97 (d, J = 8.3 Hz, 1H, ArH), 8.01 (d, J = 8.3 Hz,
2H, ArH), 9.18 (d, J = 9.0 Hz, 1H, ArH), 12.79 (s, 1H, NH);
13C NMR (400 MHz, DMSO − d6), δ (ppm): 120.3, 121.1,
121.7, 121.8, 122.2, 122.5, 122.7, 123.0, 123.3, 123.4, 123.7,
124.0, 125.4, 126.1, 128.7, 130.4, 132.2, 140.6; MS (m/z):
Calcd.346.14, found 347.02 [M+1].
2.2k 4,5-di(furan-2-yl)-2-(naphthalen-2-yl)-1H-imid-
azole (2k): Brown solid; M.p. 248−251 ◦C; FT-IR (KBr,
νmax
cm−1
)
: 3417.24 (N-H), 3057.58 (Ar-H), 1601.59
(C=C), 1555.31 (C=N); 1H NMR (500 MHz, DMSO−d6) δ
(ppm): 6.61 (d,J = 42.7 Hz, 2H, ArH), 6.80 (dd,J =
100.0 Hz, J = 2.8 Hz, 2H,ArH), 7.57 (m,2H, ArH), 7.81
(d,J = 57.2 Hz, 2H, ArH), 7.96 (d,J = 7.6 Hz, 1H,ArH),
8.01 (t,J = 10.0 Hz, 2H, ArH), 8.25 (d, J = 9.0 Hz, 1H,
ArH), 8.67 (s, 1H, ArH), 13.05 (s, 1H, NH); 13C NMR (400
MHz, DMSO − d6), δ (ppm): 102.0, 103.5, 106.4, 107.0,
114.7, 118.6, 119.4, 121.6, 121.8, 122.2, 122.7, 123.2, 123.3,
124.8, 127.9, 136.9, 137.7, 139.5, 141.3, 144.3; MS (m/z):
Calcd.326.10, found 327.11 [M+1].
2.2g 2-(naphthalen-2-yl)-4,5-diphenyl-1H-imidazole
(2g): Pale yellow solid; M.p.: 257−260 ◦C; FT-IR (KBr,
νmax
cm−1
)
: 3417.24 (N-H), 3054.69 (Ar-H), 1600.63
(C=C), 1584.01 (C=N); 1H NMR (500 MHz, DMSO−d6) δ
(ppm): 7.25 (t, J = 7.6 Hz, 1H,ArH), 7.33 (t, J = 7.6 Hz,
2H,ArH), 7.40 (t, J = 7.2 Hz, 1H, ArH), 7.47 (t, J =
7.6 Hz, 2H, ArH), 7.55 (q, J = 7.6 Hz, 4H, ArH), 7.60
(d, J = 6.9 Hz, 2H, ArH), 7.96 (q, J = 7.1 Hz, 2H,ArH),
8.02 (d, J = 9.0 Hz, 1H,ArH), 8.26 (dd, J = 8.6 Hz, J =
1.7 Hz, 1H,ArH), 8.62 (s, 1H, ArH), 12.87 (s, 1H, NH); 13C
NMR (400 MHz, DMSO−d6) δ(ppm):118.5, 118.7, 121.4,
121.6, 121.7, 122.2, 122.8, 122.9, 122.9, 123.1, 123.3, 123.5,
123.7, 126.1, 127.7, 128.0, 130.2, 132.4, 140.5; MS (m/z):
Calcd.346.14, found 347.03 [M+1].
2.2l 4-(3,4-dimethoxyphenyl)-5-(2-chlorophenyl)-2-
(naphthalen-1-yl)-1H-imidazole (2l): Off white solid;
M.p.: 185−187 ◦C; FT-IR (KBr, cm−1
)
max: 3417.24 (N-
ν
H), 3050.83 (Ar-H), 1612.20 (C=C), 1586.16 (C=N), 786
1
2.2h 4,5-bis(4-methoxylphenyl)-2-(naphthalen-1-yl)-
(C-Cl); H NMR (500 MHz, DMSO − d6) δ (ppm): 3.31
1H-imidazole (2h): Off white solid; M.p.: 172−174 ◦C; (s, 3H, -OCH3), 3.35 (s, 3H,-OCH3), 7.14 (d, J = 8.3 Hz,
FT-IR (KBr, cm−1
)
: 3418.21 (N-H), 3046.98 (Ar- 2H, ArH), 7.25 (d, J = 7.6 Hz, 2H,ArH), 7.44 (d, J =
νmax
1
H), 1614.13 (C=C), 1574.59 (C=N); H NMR (500 MHz, 8.3 Hz, 2H, ArH), 7.50 (d, J = 7.6 Hz, 2H,ArH), 7.62 (t,
DMSO − d6) δ (ppm): 3.71 (s,3H, −CH3), 3.80 (s,3H,
J = 7.6 Hz, 2H, ArH), 7.94 (d, J = 7.6 Hz, 1H,ArH), 8.00
−CH3), 6.71 (d, J = 6.9 Hz, 1H, ArH), 6.92 (m, 4H, ArH), (d, J = 7.6 Hz,2H,ArH), 9.16 (d, J = 9.0 Hz,1H, ArH),
7.41 (t, J=8.6 Hz 1H, ArH),7.61 (m, 6H, ArH), 7.79 (d, 12.67 (s, 1H, NH); 13C NMR (400 MHz, DMSO − d6) δ

62 Page 4 of 7
J. Chem. Sci.
(2019) 131:62
(ppm): 40.7, 50.0, 108.7, 109.1, 117.2, 118.0, 120.0, 120.3, and reference Butylated hydroxy anisole (BHA) were taken
120.7, 121.1, 121.5, 121.7, 122.3, 122.6, 123.2, 123.5, 123.8, in different test tubes. The volume was adjusted by adding
124.1, 125.6, 126.9, 127.7, 127.9, 128.3, 131.9, 140.5, 152.9, 500 μL of methanol. Five mL of 0.1 mM methanolic solu-
154.4; MS (m/z): Calcd.440.12, found 440.99 [M+1].
tion of 1,1-diphenyl-2-picryl hydrazyl (DPPH) was added to
the above test tubes and was shaken well for uniform con-
centration. A control without the test compounds, but with
an equivalent amount of methanol was maintained. The test
tubes were allowed to stand at room temperature for 20 min
and absorbance of the samples was measured at 517 nm. Free
radical scavenging activity was calculated by using the for-
mula. The experiments were conducted in triplicate and mean
values are reported here.
2.3 Biological activity
α
α
2.3a -Amylase inhibition assay: The -amylase inhi-
bition assay was performed using the chromogenic DNS
method reported by G. L. Miller.33 The total assay mixture
composed of 1400 μL of 0.05 M sodium phosphate buffer
α
(pH=6.9), 50 μL of -amylase and samples at concentra-
(Control OD − Sample OD)
%free radical scavenging =
X 100
Sample OD
tion 10, 50 and 100 μg/mL were incubated at 37 ◦C for 10
min. The reaction was terminated with 1 mL of DNS reagent,
placed in boiling water bath for 5 min, cooled to room tem-
perature and the absorbance measured at 540 nm. The control
3. Results and Discussion
3.1 Chemistry
α
-amylase represented 100% enzyme activity and did not con-
2,4,5-Trisubstituted imidazole derivatives (2a–2l) were
synthesized by one-pot multicomponent reaction as
shown in Scheme 1. The mechanism involves condensa-
tion followed by cyclization. In the cyclization process
the water molecule is eliminated in acidic condition to
reach the stable aromatic cyclic ring. The progress of
tain any samples of analysis. To eliminate the absorbance
produced by sample appropriate extract controls with the
extract in the reaction mixture in which the enzyme was added
after adding DNS. The liberated sugar was determined by the
help of standard maltose curve and activities were calculated
according to the following formula.
Activity in presence of compound
%inhibition/induction =
X 100
Control activity
One unit of enzyme activity is defined as the amount
of enzyme required to release one micromole of maltose
from starch per minute under the assay conditions. The
inhibitory/induction property shown by the sample was com-
pared with that of control and expressed as percent induc-
tion/inhibition. Thiswascalculatedaccordingtothefollowing
formula.
the reaction was monitored by Thin Layer Chromatog-
raphy (TLC) using petroleum ether and ethyl acetate
(3:1) medium and yield of the isolated compounds were
recorded after the purification by column chromatogra-
phy or recrystallization. Newly synthesized imidazole
derivatives were characterized by melting point, FT-
Conc.of Maltose liberated X mL of enzyme used
Activity =
X dilution factor
Mol.wt.of Maltose X incubation time (min.)
Acarbose was used as a standard inhibitor and it was
assayed at above mentioned test sample concentrations. The
assay method was similar to the above-mentioned procedure,
instead of test samples, acarbose was added. The experiments
were conducted in triplicate and results were compared to that
of test samples.
IR, NMR, and mass spectral analyses. Analytical and
spectral data of the synthesized compounds were in full
agreement with the proposed structures. In the IR spec-
tra of the compounds, the presence of NH group of
imidazole ring, aromatic C-H, C=N and aromatic C=C
bonds have been clearly identified from their respective
stretching frequencies. The number of proton signals
2.3b Antioxidant activity (Free radical scavenging
activities by DPPH assay): Free radical scavenging activ-
ity was performed using the DPPH assay method reported
by Sunil Kumar et al.34 Different concentrations (10 μg, 50
1
in H NMR spectrum and carbon signals in 13C NMR
spectrum were very much correlated with the respective
compounds. Further, the compounds molecular mass
μg and 100 μg) of the samples were dissolved in DMSO was obtained from the mass spectra of the compounds.

J. Chem. Sci.
(2019) 131:62
Page 5 of 7
62
H
O
The complete characterization of the synthesized
compounds has been given in the experimental section.
R'
N
R"
i
+
R
R
O
R'
N
H
R"
O
1
Product
2a
Structure
Yield (%)a
75
2a-2l
i: Ammonium acetate, acetic acid, 120 °C, 12–14 h.
CH3
O
N
N
H
Scheme 1. Synthesis of 2,4,5-trisubstituted imidazole
derivatives (2a–2l).
O
CH3
CH3
O
N
69
2b
N
H
O
CH3
CH3
3.2 Biological results
81
86
N
α
The -amylase inhibition activity revealed that all
2c
2d
CH3
N
H
newly synthesized imidazole derivatives showed good
inhibition at concentrations 10, 50 and 100 μg/mL.
Among the prepared imidazole compounds 2a, 2b, 2f
and 2g showed a bit higher inhibition compared to other
compounds at 10 μg/mL. The enhanced inhibition of
2,4,5-trisubstituted imidazole derivative compared with
control enzyme might be due to the N-H of imidazole
core moiety and bit enhanced variations of inhibition
might be due to the effect of functional groups attached
CH3
N
CH3
N
H
Br
46
89
N
2e
2f
Br
N
H
N
α
to imidazole. The -amylases inhibition activity of the
compounds (2a-2l) is shown in graphical representation
(Figure 1).
N
H
Among the synthesized compounds, the compounds
2d, 2g, 2k exhibit good antioxidant activity at
100 μg/mL and other compounds exhibit moderate
antioxidant activity as compared to the reference BHA.
The enhanced activity of 2d, 2g, 2k imidazole deriva-
tives may be due to 2-naphthyl substitution at second
position and phenyl, 4-methyl-phenyl, furan substitu-
tion at 4,5 positions. The results of the antioxidant
activity have been presented in Figure 2.
N
78
46
N
H
2g
2h
CH3
O
N
CH3
O
N
H
Cl
72
N
2i
N
H
Cl
78
68
65
N
2j
N
H
O
N
2k
N
H
O
H3
C
H3
C
O
O
N
2l
N
H
Cl
Figure 1. α- Amylase inhibition assay of 2,4,5-trisubsti-
tuted imidazole derivatives (2a-2l).
aIsolated yield

62 Page 6 of 7
J. Chem. Sci.
(2019) 131:62
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4. Conclusions
A
series of naphthalene incorporated 2,4,5-
trisubstituted imidazole derivatives (2a-2l) were
synthesized by one-pot multicomponent reaction and
characterized by FT-IR, NMR and mass spectral anal-
ysis. The purified final compounds were investigated
α
for their -amylase inhibition and antioxidant activities.
α
All the compounds showed excellent -amylase inhibi-
tion as compared with the control sample. Among the
screened samples, 2d, 2g, 2k exhibit good antioxidant
activity compared to BHA standard. From this study,
we conclude that the preparation of 2,4,5-trisubstituted
imidazole using substituted benzil, naphthaldehyde,
ammonium acetate and acetic acid media is the sim-
plest method to construct imidazole ring. The biological
study of the title compounds showed promising antioxi-
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α
dant and -amylase inhibition activities. Hence, they are
ideally suited for further notification to obtain more effi-
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α
imidazoles for -glucosidase inhibition to treat diabetes
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Acknowledgements
The authors are thankful to the Principal and the staff of
Smt. Indira Gandhi Government First Grade Women’s Col-
lege, Sagar, Principal, University College of Science, Tumkur
and Tumkur University administration for their support and
encouragement.
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