Synthesis, in vitro and in silico studies of naphthalene pyrazoline prop-2-en-1-one derivatives

Article abstract of DOI:10.14233/ajchem.2020.22654

The synthesized new naphthalene pyrazoline prop-2-en-1-one derivatives (NDPP 1-8) were obtained by the Michael addition reaction of ethyl propanoate, hydrazine hydrate with NPD as a multicomponent scaffold. (E)-1-(naphthalen-3-yl)-3-phenylprop-2-en-1-one (NPD) was formed from 2-acetyl naphthalene and substituted aldehyde via Claisen-Schmidt condensation reaction. The NDPP skeleton structures were confirmed by infrared, ¹H & ¹³C NMR spectral data and elemental analysis. The structure of NDPP compounds was subjected to molecular docking and ADME studies. The result of ADME prediction, compound NDPP 2, which contains electron withdrawing -Cl group has high drug-likeness value 4.21 than the compounds NDPP 4 and 7 which had electron donating CH3 and OCH3 group shows the drug-likeness value 2.62. The NDPP 2 also has high drug score 0.63 than NDPP 4 and NDPP 7 have drug score 0.60 and 0.69, respectively. Docking studies shows that compound NDPP 5 which also contain electron withdrawing NO2 group has good binding affinity value -8.8 Kcal/mol were docked with 1UAG protein. These compounds showed good drug-likeness value 2.25 and drug score 0.65. in vitro Studies have a high inhibition value for the same NO2 substituted derivative. All the compounds have higher binding affinity value than standards binding affinity value.

Full text of DOI:10.14233/ajchem.2020.22654

Asian Journal of Chemistry; Vol. 32, No. 8 (2020), 1849-1856
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2020.22654
Synthesis, in vitro and in silico Studies of Naphthalene Pyrazoline Prop-2-en-1-one Derivatives
*,
B. PRABHA, C. RAJA, S. NATHIYA and M.R. EZHILARASI
Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore-641021, India
*
Corresponding author: E-mail: mrezhilarasi@gmail.com
Received: 27 January 2020; Accepted: 13 March 2020;
Published online: 27 July 2020;
AJC-19957
The synthesized new naphthalene pyrazoline prop-2-en-1-one derivatives (NDPP 1-8) were obtained by the Michael addition reaction of
ethyl propanoate, hydrazine hydrate with NPD as a multicomponent scaffold. (E)-1-(naphthalen-3-yl)-3-phenylprop-2-en-1-one (NPD)
was formed from 2-acetyl naphthalene and substituted aldehyde via Claisen-Schmidt condensation reaction. The NDPP skeleton structures
1
13
were confirmed by infrared, H & C NMR spectral data and elemental analysis. The structure of NDPP compounds was subjected to
molecular docking and ADME studies. The result of ADME prediction, compound NDPP 2, which contains electron withdrawing -Cl
group has high drug-likeness value 4.21 than the compounds NDPP 4 and 7 which had electron donating CH
drug-likeness value 2.62. The NDPP 2 also has high drug score 0.63 than NDPP 4 and NDPP 7 have drug score 0.60 and 0.69, respectively.
Docking studies shows that compound NDPP 5 which also contain electron withdrawing NO group has good binding affinity value -8.8
Kcal/mol were docked with 1UAG protein. These compounds showed good drug-likeness value 2.25 and drug score 0.65. in vitro Studies
have a high inhibition value for the same NO substituted derivative. All the compounds have higher binding affinity value than standards
binding affinity value.
3
and OCH
3
group shows the
2
2
Keywords: Naphthalene pyrazoline, Prop-2-en-1-one, ADME.
Nabumetone another important anti-inflammatory drug used
to blocks the COX-2 activity in human system [19]. The bedaq-
uiline used as a antituberculosis drug which is approved by
FDA [20] and rifampicin also a drug, used in the treatment of
tuberculosis [21]. Tolnaftate and natifine are the drugs used as
an antifungal [16,22,23]. Nafcillin is an antibiotic and parti-
cularly used to the treatment of infections, which are caused
by gram positive bacteria [16,24].
Present decades, computational method is consider as one
of the best and beneficial method to analyses the chemical
structure of the compounds [25] and these are accepted over
the world. Many applications are available to predict the various
pharmacokinetics property of the chemical compounds [26,27].
Molecular docking studies are used to predict the affinity value
and the manner of interaction of organic structured compounds
with various proteins. This method is quite effective to predict
the binding score and the binding of small or macromolecules
with protein targets, which helps to identify the medicinal appli-
cations of compounds in various fields [28]. ADME property
prediction of the compounds helps to find out their drug-
likeness and toxicity.
INTRODUCTION
Infectious diseases are believed to occur sometimes due
to resistance to the action of drugs. Some of the infectious disease
may lead to many dangerous health conditions in humans. To
overcome this problem, we need to design and create new
compounds that are averse to infectious pathogens with a high
number of multidrug properties along with biodegradable, less
toxic and good soluble properties. Pyrazole is a five-membered
heterocyclic core with a wide pharmaceutical impact [1]. The
alternative presence of C-N, C-C and C-N bonds in the pyrazole
ring formed by cross linking of electrophile or condensation
of unsaturated ketones with hydrazine [2-4] and the pyrazole
ring structure also formed by Schiff base reaction [5]. The
pyrazoles moiety has antimicrobial [6,7], antimalarial [8], anti-
inflammatory [9], anti-proliferative [10], anti-tumor [11] and
anti-hyperglycemic [12] properties and is used in the field of
herbicides [13], agrochemicals [14], corrosion inhibition [15]
etc.
Naproxen containing naphthalene moiety is a propionic
acid class of non-steroidal anti-inflammatory drug [16-18].
This is an open access journal, and articles are distributed under the terms of the Attribution 4.0 International (CC BY 4.0) License. This
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1
850 Prabha et al.
Asian J. Chem.
The naphthalene pyrazoline prop-2-en-1-one derivatives
1-(3-(4-Bromophenyl)-4,5-dihydro-5-(naphthalen-3-
(
NDPP 1-8) were synthesized by Michael addition reaction
yl)pyrazol-1-yl)propan-1-one (NDPP-1):Yield 89%; yellow;
-1
as multicomponent ones. The synthesized NDPP compounds
m.p.: 416 ºC; m.w.: 407.3; IR (KBr, νmax, cm ): 1472.47 (C=N),
1
13
structure were confirmed by IR, H & C NMR spectral and
elemental analysis. The confirmed structures were screened
to in-silico ADME and molecular docking in-vitro antimicrobial
studies.
1660.34 (C=O), 1135.00 (C-N), 3128.18 (Ar-CH), 2902.20 (Al-
1
CH), 805, 605 (Ar-ring); H NMR (CDCl
3
, 400 MHz, ppm)
3.23 (dd, J4a,4e = 3.8 Hz, J4a,5a = 17.4 Hz, 2H, H-4a), 3.75 (dd,
4e,4a = 12.2 Hz , J4e,5a = 17.0 Hz, 2H, H-4e), 5.56 (dd, J5a,4a
J
=
4
2
.2 Hz, J5a,4e = 11.4 Hz, 1H, H-5a), 1.14-1.18 (t, CH
3
), 2.81-
, 100 MHz,
), 36.15 (C2′, CH ),
EXPERIMENTAL
13
.84 (m, CH
2
), 7.194-8.085 (Ar, H); C NMR (CDCl
3
The physical data of NDPP derivatives were done by using
suitable instruments. The instruments Shimadzu 8400s, Bruker
00 MHz and 100 MHz were used to evaluate the infrared, H
δ ppm): 172.12 (C=O), 14.02 (C3′, CH
153.18 (C-3), 41.65 (C-4), 59.13 (C-5), 140.28, 134.58, 133.20
(ipso carbons), 127.08-124.23 (Ar-C). Elemental analysis of
C
2
3
1
4
&
13
C NMR values of the target compounds in the usual range.
22
H
19
N OBr calcd. (found) %: C, 64.86 (64.46); H, 4.66 (4.63),
2
Synthesis of (E)-1-(naphthalen-3-yl)-3-phenylprop-2-
N, 6.87 (6.37), O, 3.93 (3.93), Br, 19.65 (19.32).
en-1-one (NPD): The literary method was followed to synthesize
NPD compound [29]. In brief, substituted benzaldehyde (1 mol)
and 2-acetyl naphthalene (1 mol) were mixed in 250 mL Erlen-
meyer containing NaOH dissolved ethanol. The reaction mixture
was stirred for 3 h with ice cold conditions. The TLC was used
to monitor the completion of reaction. The reaction mixture
was poured into 400 mL beaker containing crushed ice and kept
in a refrigerator for overnight and then filtered, washed with
excess of water, dried and recrystallized from ethanol.
Synthesis of 1-(4,5-dihydro-5-(naphthalene-3-yl)-3-
phenylpyrazole-1-yl)propan-1-one (NDPP): Chalcone deri-
vative (1 mol) was taken in the round bottom flask containing
ethyl proponate and hydrazine hydrate (1 mol) was added drop
wise. The whole mixture was placed in the heating mantle for
1-(3-(4-Chlorophenyl)-4,5-dihydro-5-(naphthalen-3-
yl)pyrazol-1-yl)propan-1-one (NDPP-2): Yield 94%; pale
-1
yellow; m.p.: 386; m.w.: 362.85; IR (KBr, νmax, cm ): 1477.47
(C=N), 1662.64 (C=O), 1138.00 (C-N), 3138.18 (Ar-CH),
1
2910.12 (Al-CH), 750.31(Ar-ring); H NMR (CDCl
3
, 400
MHz, δ ppm) 3.25 (dd, J4a,4e = 4 Hz, J4a,5a = 17.6 Hz, 2H, H-4a),
3.85 (dd, J4e,4a = 12.4 Hz , J4e,5a = 17.2 Hz, 2H, H-4e), 5.58 (dd,
J
5a,4a = 4 Hz, J5a,4e = 11.6 Hz, 1H, H-5a), 1.19-1.2 (t, CH
3
), 2.83-
, 100 MHz,
), 36.17 (C2′, CH ), 153.20
(C-3), 41.95 (C-4), 59.63 (C-5), 140.68, 134.18, 133.40 (ipso
carbons), 129.10-123.29 (Ar-C). Elemental analysis of C22
13
2.86 (m, CH
δ ppm): 171.61 (C=O), 14.04 (C3′, CH
2
), 7.092-7.985 (Ar, H); C NMR (CDCl
3
2
3
H
19
N
2
OCl calcd. (found) %: C, 72.72 (71.86); H 5.23 (5.23); N,
7.71 (7.37); O, 4.40 (4.43); Cl, 9.64 (9.32).
1
6-18 h of reflux. The TLC was used to monitor the completion
of the reaction.After that, the reaction mixture transferred into
00 ml beaker contain crushed ice and it was kept overnight
1-(3-(2-Chlorophenyl)-4,5-dihydro-5-(naphthalen-3-
yl)pyrazol-1-yl)propan-1-one (NDPP-3): Yield 92%; pale
-1
4
yellow; m.p.:386 ºC; m.w.: 362.85; IR (KBr, νmax, cm ): 1427.32
at room temperature. The target compound was filtered, dried
and its purity also checked by TLC with 9:1 petroleum ether:
chloroform as a solvent (Scheme-I).
(C=N), 1662.64 (C=O), 1035.77 (C-N), 3050.65 (Ar-CH),
1
2931.80 (Al-CH), 653.12,724.23 (Ar-ring); H NMR (CDCl
3
,
400 MHz, δ ppm): 3.16 (dd, J4a,4e = 3.2 Hz, J4a,5a = 17.6 Hz, 2H,
X
O
CHO
NaOH in EtOH
h stirring
CH3
+
O
3
NPD(1-8)
1
6
-(naphthalen-
-yl)ethanone
(
E)-1-(naphthalen-3-yl)-3-phenylprop-2-en-1-one
X
Propionic acid
Substituted
Benzaldehyde
1
4 h
Reflux
O H N
2
H
H
NH2
X = NDPP1: 4-Br; NDPP2: 4-Cl; NDPP3: 2-Cl;
NDPP4: 4-CH ; NDPP5: 4-NO ; NDPP6: 4-F;
O
3
2
NDPP7: 4OCH ; NDPP8: 4-H
N
3
N
X
1
-(4,5-dihydro-5-(naphthalen-3-yl)-3-phenylpyrazol-1-yl)propan-1-one
NDPP(1-8)
Scheme-I: Synthetic pathway for the synthesized NDPP 1-8 compounds

Vol. 32, No. 8 (2020)
Synthesis, in vitro and in silico Studies of Naphthalene Pyrazoline Prop-2-en-1-one Derivatives 1851
H-4a), 3.74 (dd, J4e,4a = 12.2 Hz , J4e,5a = 17.4 Hz, 2H, H-4e),
2H, H-4e), 5.52 (dd, J5a,4a = 3.6 Hz , J5a,4e = 11.2 Hz, 1H, H-5a),
5
.57 (dd, J5a,4a = 6.2 Hz , J5a,4e = 10.2 Hz, 1H, H-5a), 0.97-1.01
0.98-1.02 (t, CH ), 2.73-2.84 (m, CH ), 7.102-7.975 (Ar, H);
, 100 MHz, δ ppm): 171.75 (C=O), 14.00 (C3′
), 36.08 (C2′, CH ), 153.17 (C-3), 41.86 (C-4), 59.63 (C-5),
142.42, 140.66, 133.16 (ipso carbons), 130.13-125.88 (Ar-C).
Elemental analysis of m.f. C23 calcd. (found) %: C,
3
2
13
13
(
(
(
t, CH
CDCl
C
3
), 2.30-2.86 (m, CH
, 100 MHz, ppm): 171.61 (C=O), 14.04 (C3′, CH
), 153.20 (C-3), 41.95 (C-4), 59.63 (C-5), 140.68,
34.18, 133.40 (ipso carbons), 129.10-123.29 (Ar-C). Elemental
analysis of C22 OCl calcd. (found) %: C, 72.72 (71.86);
H, 5.23 (5.23); N, 7.71 (7.37); O, 4.40 (4.43); Cl, 9.64 (9.32).
-(3-(4-Methylphenyl)-4,5-dihydro-5-(naphthalen-3-
yl)pyrazol-1-yl)propan-1-one (NDPP-4): Yield 90%; pale
2
), 6.895-7.776 (Ar, H); C NMR
C NMR (CDCl
CH
3
,
3
2
), 36.17
2
3
2′, CH
3
1
H
22
N
2
O
2
H N
19 2
77.05 (76.96), H, 6.14 (6.12); N, 7.81 (7.65); O, 8.93 (8.83).
1-(4,5-Dihydro-5-(naphthalene-3-yl)-3-phenylpyrazole-
1-yl)propan-1-one (NDPP-8):Yield 82%; pale yellow; m.p.:
1
-1
343 ºC; m.w.: 328.16; IR(KBr, νmax, cm ): 1440.12 (C=N),
-1
Yellow; m.p.: 367 ºC; m.w.: 342.43; IR (KBr, νmax, cm ): 1447.32
1656.42 (C=O), 1095.25 (C-N), 3060.72 (Ar-CH), 2971.24
1
(
C=N), 1660.42 (C=O), 1115.77 (C-N), 3065.24 (Ar-CH),
(Al-CH), 784.32, 823.13 (Ar-ring); H NMR (CDCl
3
, 400 MHz,
1
2
4
2
5
911.23 (Al-CH), 792.32, 801.21 (Ar-ring); H NMR (CDCl
3
,
δ ppm): 3.19 (dd, J4a,4e = 4 Hz, J4a,5a = 17.4 Hz, 2H, H-4a), 3.74
(dd, J4e,4a = 12.2 Hz , J4e,5a= 17.4 Hz, 2H, H-4e), 5.62 (dd, J5a,4a
00 MHz, δ ppm): 3.14 (dd, J4a,4e = 3.8 Hz, J4a,5a = 17.8 Hz,
H, H-4a), 3.78 (dd, J4e,4a = 12.2 Hz , J4e,5a= 17.4 Hz, 2H, H-4e),
.56 (dd, J5a,4a = 3.8 Hz , J5a,4e = 11.4 Hz, 1H, H-5a), 0.97-1.01
= 3.8 Hz , J5a,4e = 11.4 Hz, 1H, H-5a), 0.99-1.12 (t, CH
3
), 2.81-
), 7.095-7.895 (Ar, H); C NMR (CDCl , 100
MHz, δ ppm): 171.41 (C=O), 13.92 (C3′, CH ), 36.03 (C2′
CH ), 153.16 (C-3), 41.96 (C-4), 59.44 (C-5), 140.99, 136.38
(ipso carbons), 130.53-125.83 (Ar-C). Elemental analysis of
O calcd. (found) %: C, 80.44 (80.26); H, 6.09 (6.03);
13
2.84 (m, CH
2
3
13
(t, CH
3
), 2.74-2.82 (m, CH
3
2
), 7.132-7.965 (Ar, H); C NMR
, 100 MHz, δppm): 171.75 (C=O), 14.00 (C3′, CH ), 36.08
), 153.17 (C-3), 41.86 (C-4), 59.63 (C-5), 142.93,
2
,
(CDCl
2
3
(C
2′, CH
3
1
39.71, 140 (ipso carbons), 130.13-125.88 (Ar-C). Elemental
analysis of C23 O calcd. (found) %: C, 80.70 (79.86); H,
.43 (6.23); N, 8.18 (7.97), O, 4.67 (4.53).
-(3-(4-Nitrophenyl)-4,5-dihydro-5-(naphthalen-3-yl)-
pyrazol-1-yl)propan-1-one (NDPP-5):Yield 85%; brownish
C
22
H
20
N
2
H
22
N
2
N, 4.26 (4.23); O, 4.87 (4.83).
6
Antimicrobial activity: The disk diffusion method is used
to carry out the antimicrobial studies of synthesized NDPP
compounds. Sterilized inoculums and sterile swab were used.
The C. albicans strain was used for the screening of antifungal
study. Ciprofloxacin and clotrimazole were used as standard
drugs in the microbial studies. Other steps were adopted from
the reference [5].
1
-1
yellow; m.p.: 392 ºC; m.w.: 375; IR(KBr, νmax, cm ): 1457.21
(
C=N), 1659.64 (C=O), 1095.25 (C-N), 3002.12 (Ar-CH),
1
2
952.30 (Al-CH), 692.21,795.54 (Ar-ring); H NMR (CDCl
3
,
400 MHz, δ ppm): 3.16 (dd, J4a,4e = 4 Hz, J4a,5a = 17.6 Hz, 2H,
H-4a), 3.84 (dd, J4e,4a = 12.4 Hz, J4e,5a = 17.6 Hz, 2H, H-4e), 5.66
dd, J5a,4a = 4.2 Hz, J5a,4e = 11.4 Hz, 1H, H-5a), 0.98-1.02 (t,
Molecular docking:TheAuto dock 4.2.5.1 version program
was used for the molecular docking studies of synthesized
NDPP derivatives. The given literary method was followed to
find the docking scores [29].
(
13
CH
00 MHz, δ ppm): 171.53 (C=O), 14.01 (C3′, CH
CH ), 153.26 (C-3), 42.09 (C-4), 59.60 (C-5), 141.43, 139.71
ipso carbons), 129.87-124.18 (Ar-C). Elemental analysis of
calcd. (found) %: C, 70.77 (70.56); H, 5.09 (5.02);
N, 11.26 (11.23); O, 12.86 (12.46).
-(3-(4-Fluorophenyl)-4,5-dihydro-5-(naphthalen-3-
yl)pyrazol-1-yl)propan-1-one (NDPP-6):Yield 84%; yellow;
3
), 2.74-2.89 (m, CH
2
), 7.114-8.098 (Ar, H); C NMR (CDCl
3
,
1
2
), 36.21 (C2′
,
3
ADME studies: The NDPP compound structure was subj-
ected to Absorption, Distribution, Metabolism and Excretion
(ADME) studies using Osiris online tool. The tool has the basic
information about solubility (S), log P, polar surface area (TPSA),
hydrogen bond acceptor (Hd.Ac.), hydrogen bond donor (Hd.
Dn.), drug-likeness score and drug score. The above parameters
are helpful to understand the ADME property of any drugs or
organic molecule. The compound has a drug property, which
means it must obey the rule of five described by Lipinski. The
Lipinski′s rules are: the compound must have molecular weight
≤ 500, Hydrogen bond acceptor ≤ 10, hydrogen bond donor
≤ 5, log p ≤ 5 and molar refractivity ≤ 140. The other most
important properties of the compounds are that they have polar
surface area range between 7 to 200, S range above-4, the drug
score value above 0.5 and drug-likeness score as in positive
values for synthesized organic compounds [30].
(
C H
22 19
N O
3 3
1
-1
m.p.: 357 ºC; m.w.: 346.15; IR(KBr, νmax, cm ): 1447.12 (C=N),
1
663.14 (C=O), 1145.17 (C-N), 3080.82 (Ar-CH), 2951.78
1
(
Al-CH), 784.32, 823.13 (Ar-ring); H NMR (CDCl
MHz, δ ppm): 3.18(dd, J4a,4e = 3.8 Hz, J4a,5a = 17.4 Hz, 2H, H-4a),
.76 (dd, J4e,4a = 12.2 Hz , J4e,5a= 17 Hz, 2H, H-4e), 5.51 (dd,
5a,4a = 3.6 Hz , J5a,4e = 11.8 Hz, 1H, H-5a), 0.97-1.0 (t, CH ),
), 6.956-7.984 (Ar, H); C NMR (CDCl
00 MHz, δ ppm): 171.41 (C=O), 13.92 (C3′, CH ), 36.03 (C2′
), 153.16 (C-3), 41.96 (C-4), 59.44 (C-5), 140.19, 134.38
ipso carbons), 130.53-126.93 (Ar-C). Elemental analysis of
3
, 400
3
J
2
1
3
13
.72-2.85 (m, CH
2
3
,
2
,
CH
(
3
C
22
H
19
N OF calcd. (found) %: C, 76.30 (76.26); H, 5.49 (5.43);
2
RESULTS AND DISCUSSION
N, 8.09 (8.07); O, 4.62 (4.53); F, 5.49 (5.32).
-(3-(4-Methoxyphenyl)-4,5-dihydro-5-(naphthalen-3-
yl)-pyrazol-1-yl)propan-1-one (NDPP-7): Yield 92%;
yellowish white; m.p.: 389 ºC; m.w.: 358.17; IR (KBr, νmax
1
The target NDPP compounds were synthesized from the
reactant α,β-unsaturated ketone with ethyl proponate and
hydrazine hydrate. The Michael addition reaction was perfor-
med to create the target NDPP (1-8) compounds as a multi-
component reaction. Multicomponent reaction is the best reaction
method for organic synthesis nowadays due to its less reaction
time and minimum or no solvents usage. The starting material
,
-1
cm ): 1435.24 (C=N), 1658.23 (C=O), 1098.05 (C-N), 3100.61
1
(
(
1
Ar-CH), 2982.54 (Al-CH), 768.21, 813.45 (Ar-ring); H NMR
CDCl
7.8 Hz, 2H, H-4a), 3.80 (dd, J4e,4a = 12.2 Hz , J4e,5a = 17.4 Hz,
3
, 400 MHz, δ ppm): 3.18 (dd, J4a,4e = 3.8 Hz, J4a,5a =

1
852 Prabha et al.
Asian J. Chem.
TABLE-1
ADME PREDICTION VALUE OF TARGET COMPOUNDS NDPP 1-8
Compd.
log P
5.60
5.48
5.48
5.22
4.97
4.98
4.81
4.6
m.w.
Hd. Ac.
Hd. Dn.
Mol. Ref.
108.64
105.55
105.45
106.84
107.52
101.35
106.84
100.94
No. of violation
Solubility
-6.33
-6.23
-6.23
-5.84
-5.95
-5.81
-5.51
-5.49
TPSA
32.67
32.67
32.67
32.67
72.98
32.67
41.90
32.67
1
2
3
4
5
6
7
8
407.31
362.86
362.86
342.43
373.14
346.40
358.44
328.41
3
3
3
3
6
3
4
3
0
0
0
0
1
0
0
0
1
0
0
0
0
0
0
0
NPD was synthesized from Claisen-condensation between
substituted benzaldehyde and 2-acetyl naphthalene. The NDPP
compound structures were elucidated with the help of infrared
The target compound NDPP-2 which has electron with-
drawing substitution exhibit high drug-likeness value 4.21 than
the compounds NDPP-4 and 7, which have electron donating
substitution. Also the compound NDPP-2 has high drug score
value 0.63 than the compounds NDPP-4 have a drug score 0.60.
The NDPP-5 have good drug-likeness value 2.25 and drug score
0.65. All the NDPPs compounds have + values in the drug-
likeness column and have the best drug score above 0.5. This
showed that the synthesized NDPP 1-8 compounds must have
pharmacokinetics property. So the target compounds have the
ability to act as a drug. The drug-likeness score and drug score
are tabulated in Table-2.
1
13
and H & C NMR data. The confirmed structures were screened
by in silico and in vitro screening methods to find the drug-
likeness, binding ability and inhibition rate of the targets.
IR studies:The IR spectrum of NDPP-2 compounds shows
-1
that absorption peak appeared in the range 1477.47 cm due to
presence of C=N stretching of pyrazole ring. The absorption peaks
-1
present at 1662.64 and 1138.00cm belong to the C=O and
C-N stretching, respectively. The aromatic and aliphatic absor-
ption frequencies appeared in the range of 3138.18 and 2910.12
-1
cm . The aromatic ring stretching also appeared in the range of
-1
TABLE-2
8
00-601 cm .
1
1
DRUG-LIKENESS AND DRUG SCORE
VALUE OF COMPOUNDS NDPP 1-8
H NMR studies: The H NMR of NDPP-2 compound
exhibits dd value at 3.25 ppm J4a,4e = 4 Hz and J4a,5a = 17.6 Hz
allocated to the H-4a proton of pyrazole moiety.Another two dd
values appeared at 3.85 ppm (J4e,4a = 12.4 Hz & J4e,5a = 17.2 Hz
due to presence of H-4e proton and 5.58 ppm (J5a,4a = 4 Hz &
Drug-likeness
Drug score
0.52
Drug-likeness
2.25
Drug score
0.65
1.20
4.21
2.15
1.19
0.63
0.60
0.60
2.67
2.62
2.47
0.68
0.69
0.69
J5a,4e = 11.6 Hz) assigned for H-5a of pyrazole moiety. The signal
present at δ1.19-1.20 ppm as a triplet which belongs to the methyl
group of propanoyl chain and the multiplet appeared in the range
Docking results: All the target compounds NDPP 1-8
2
.83-2.86 ppm attribute to the -CH
2
of propanoyl chain.
have high binding score above -8.0. The docking result also
13
C NMR studies: The carbon NMR spectrum of comp-
shows that the electron-withdrawing NDPP-5 (-NO ) group
2
13
ound NDPP-2 shows that C NMR resonance at 171.61 ppm
is attributed due to C=O. The C NMR resonance at 14.04 ppm
is due to the presence of methyl group of propanoyl moiety.
The C NMR resonance at 36.17 ppm is assigned to ethyl group
of propanoyl moiety while 153.20 ppm is attributed due to C-3
of pyrazole ring. The C NMR resonances of 41.95 and 59.63
ppm are attributed due to C-4 and C-5 of pyrazole ring, respe-
ctively. The C NMR resonance at 140.68, 134.18 and 133.40
ppm were ipso carbons. The aromatic carbons appeared in the
ranges of 129.10-123.29 ppm.
has the best high binding affinity value among the other NDPP
compounds and the standard drug.All the target NDPP comp-
ounds have high binding affinity value rather than the standard
ciprofloxacin. The compound NDPP-5 shows the 4 Hydrogen
bond interaction between LYS A: 115, GLY A: 114, LYS A:
13
13
13
319 and SERA: 116 and NO substitution and one hydrophobic
2
bond interaction between LEU A: 416 and aromatic ring of
naphthalene moiety without unfavourable bonds.
13
The NDPP-1 compound has affinity score -8.3 with H-bond
interaction between carbonyl group in the propionoic acid chain
and LYSA: 319, hydrophobic interaction through naphthalene
ring with ALA A: 414, LEU A: 416; NDPP-2,4 compounds
have affinity score -8.2, -8.3 with two hydrogen bond interaction
SER A: 415 and LEU A: 416; NDPP-3 also has affinity score
-8.2 and two hydrogen bond interactions LEU A: 15, THR A:
16; NDPP-6 has -8.3 as its affinity score with one hydrogen bond
interaction ARG A: 313; NDPP-6,7 has second high affinity
score -8.7.
ADME property:All the synthesized compounds [NDPP
-8] have excellent ADME prediction values. The drug-
1
likeness score of all the compounds in the positive values
indicates that all the compounds have drug ability property.
Mostly all the target compounds in silico ADME values are
adopted with the Lipinski′s rule of five. All the compounds
should obey the Lipinski′s rule with 0 violations except NDPP-
1, which has one violation. The polar surface area value is high
for NDPP-5 and NDPP-7 compounds rather than others in
the series. The target compounds have solubility in the range
of -6 to -5 (Table-1).
The binding affinity scores, hydrogen bond interaction
and hydrophobic interaction are given in Table-3 and the 2D
& 3D image of docking results given in Table-4.

Vol. 32, No. 8 (2020)
Synthesis, in vitro and in silico Studies of Naphthalene Pyrazoline Prop-2-en-1-one Derivatives 1853
Antimicrobial result: The result of NDPP compounds
TABLE-3
MOLECULAR DOCKING RESULTS FOR
PYRAZOLE DERIVATIVES NDPP 1-8 DOCKED
WITH BACTERIAL PROTEIN 1UAG
binding affinity was subjected to screening activity against S.
pyogenes, S. aureus and Gram-negative E.coli, P. aeruginosa
bacterial strains, while the fungal activity was done by using
C. albicans fungal strain. The study was done in the concentra-
tion range 1 mg/mL and the inhibition values are given in the
Binding
affinity score
H-Bond
interaction
Hydrophobic
interaction
Compound
NDPP-1
-8.3
-8.2
-8.2
-8.3
LYS A: 319
ALA A: 414
LEU A: 416
LYS A: 348
ARG A: 186
ILE A: 74
Table-5. The NDPP-2, 5, 6 (-Cl, -NO , -F) substitutions have
2
high inhibition value averse to Gram negative and Gram-positive
strains. The fungal activity data of NDPP compounds showed
NDPP-2
NDPP-3
NDPP-4
SER A: 415
LEU A: 416
LEU A: 15
THR A: 16
SER A: 415
LEU A: 416
that the electron donating CH group has better inhibition value
3
against C. albicans strain.
PHE A: 422
LYS A: 348
ARG A: 186
Conclusion
Naphthalene pyrazoline prop-2-en-1-one derivatives (NDPP
NDPP-5
-8.8
LYS A: 115
GLY A: 114
LYS A: 319
SER A: 116
ARG A: 313
–
1
-8) were successfully synthesized and characterized from the
LEU A: 416
multicomponent reaction via Michael addition method. The
molecular docking andADME results indicated that compound
NDPP-5, which has a large Total polar surface area (TPSA),
gets a high binding affinity score and a high number of hydrogen-
bonding. Moreover, compound NDPP-5 also exhibited excellent
inhibition values in the antibacterial studies compared to other
NDPP compounds. Finally, it is concluded that compound
NDPP 5 has high total polar surface area exhibiting excellent
scores in the in-silico as well as in in-vitro studies.
NDPP-6
NDPP-7
NDPP-8
-8.3
-8.7
-8.7
LEU A: 333
–
LEU A: 333
–
ASN A: 178
ASN A: 271
GLU A: 327
Ciprofloxacin
-7.7
ALA A: 328
TABLE-4
2D AND 3D IMAGE FOR THE SYNTHESIZED COMPOUNDS (NDPP 1-8)
Compound
2D IMAGE
3D IMAGE
NDPP-1
NDPP-2

1
854 Prabha et al.
Asian J. Chem.
NDPP-3
NDPP-4
NDPP-5
NDPP-6

Vol. 32, No. 8 (2020)
Synthesis, in vitro and in silico Studies of Naphthalene Pyrazoline Prop-2-en-1-one Derivatives 1855
NDPP-7
NDPP-8
Ciprofloxacin
TABLE-5
in vitro STUDIES VALUES OF COMPOUND NDPP 1-8 AT 1.0 mg/mL
Bacterial strain
S. pyogenes
Fungal strain
Compound
S. aureus
18
E. coli
17
23
16
18
21
17
20
18
P. aeruginosa
C. albicans
NDPP-1
NDPP-2
NDPP-3
NDPP-4
NDPP-5
NDPP-6
NDPP-7
NDPP-8
16
21
14
19
20
16
20
15
17
17
24
19
18
21
19
20
16
22
12
15
14
16
17
13
19
10
24
23
20
19
24
18
21
17
26
Ciprofloxacin/Clotrimazole
19

1
856 Prabha et al.
Asian J. Chem.
1
5. C. Verma, V.S. Saji, M.A. Quraishi and E.E. Ebenso, J. Mol. Liq., 298,
CONFLICT OF INTEREST
The authors declare that there is no conflict of interests
1
11943 (2020);
https://doi.org/10.1016/j.molliq.2019.111943
6. S. Markar, T. Saha and S.K. Singh, Eur. J. Med. Chem., 161, 252 (2019);
https://doi.org/10.1016/j.ejmech.2018.10.018
7. R.N. Brogden, R.M. Pinder, P.R. Sawyer, T.M. Speight and G.S. Avery,
Drugs, 9, 326 (1975);
1
1
regarding the publication of this article.
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