Journal of Molecular Structure 1246 (2021) 131183

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Journal of Molecular Structure

journal homepage: www.elsevier.com/locate/molstr

Design, one-pot synthesis, molecular docking study, and antibacterial

evaluation of novel 2H-chromene based imidazo[1,2-a]pyridine
derivatives as potent peptide deformylase inhibitors
Nilima Priyadarsini Mishra a, Seetaram Mohapatra a,∗, Chita Ranjan Sahoo b,
Bishnu Prasad Raiguru a, Sabita Nayak a, Subhrakant Jena c, Rabindra Nath Padhy b,∗
a
Organic Synthesis Laboratory, Department of Chemistry, Ravenshaw University, Cuttack, Odisha 753003, India
b
Central Research Laboratory, IMS & Sum Hospital, Siksha ‘O’ Anusandhan University, Bhubaneswar, Odisha 52003, India
c
National Institute of Science Education and Research, Bhubaneswar, Odisha 752 050, India

a r t i c l e i n f o a b s t r a c t

Article history: An efficient, environmentally friendly, one-pot three-component synthesis of a series of 2H-chromene-
Received 27 February 2021 based imidazo[1,2-a]pyridines had been designed and were synthesized. This protocol was developed by
Revised 19 July 2021
the reaction of substituted 2H-chromene aldehydes and 2-aminopyridine in a mixture of nitroalkane and
Accepted 24 July 2021
DMF under microwave irradiation at 60W, 100°C in 15 min with the presence of FeCl3 as the catalyst. The
Available online 28 July 2021
products were obtained in excellent yields with high functional group tolerance. All these compounds had
Keywords: been investigated further in vitro for evaluation of antibacterial potency by agar-well diffusion method
2H-chromene against human pathogenic Gram-positive and Gram-negative bacteria, with the determination of min-
Imidazo[1,2-α ]pyridines imum inhibitory concentration (MIC) values. Indeed, compound 13i strongly inhibited peptide deformy-
Antibacterial lase (MIC = 16 μg/ml) in the Gram-negative Escherichia coli, in silico. From structure-activity relationships
Peptide deformylase inhibitor based on the biological and molecular docking results and the potent antibacterial activities, it could be
Molecular docking study
stated that the selected synthetic compounds could be used as potent drugable antibacterial agents.
© 2021 Elsevier B.V. All rights reserved.

1. Introduction Moreover, any viral infection drastically degrades the immunity-

People of all age groups get decimated each year in each geo-
graphic zone from bacteria as balanced parasites, e.g., suppurative
infections from the Gram-positive bacterium Staphylococcus aureus
[1] and staggering tuberculosis and leprosy bacilli [2]; or from
destructive parasites, namely, diarrhea/ dysentery from enterococci
and Vibrio cholera with instantly triggering of a life-threatening sit-
uation at a blistering pace, despite the use of a plethora of emu-
lating drugs for common and uncommon infectious diseases [3].
Moreover, mortality of children under the age of 5 in low-income
and middle-income countries in South-East Asia, tribal and rural
India, sub-Saharan Africa, Latin America has been always a major
concern of UNICEF and WHO respiratory/chest/urinary tract infec-
tions are the most commonplace infections causing morbidity and
premature mortality [4,5]. Adults often fall into the vicious cycle,
“Poverty begets illness, in turn, illness begets poverty”, in several
developing countries.
∗
Corresponding authors.
E-mail addresses: seetaram.mohapatra@gmail.com (S. Mohapatra),
rnpadhy54@gmail.com (R.N. Padhy).
strength of a body, resulting in the consequent opportunistic bac-
terial infections from the environment or the dormant resident
pathogenic bacteria of the body, as in the COVID-19 pandemic
pneumonia-causing Klebsiella pneumoniae devastating human, for
instance [6]. The most unfortunate situational tragedy in the hu-
man body is that one virulent bacterium causing an infection in-
fects several innards sometimes with ‘toxic shock syndrome’ tak-
ing the total grip of the body till the body is decimated. Thus,
whether for a patient complaining of an infectious urinary/ respira-
tory/wound ailment or if a surgeon after a surgical episode prefers
to prescribe an antibiotic of a higher generation pre-emptively
(called as empiric therapy in ‘antimicrobial stewardship program’)
to be sure that the infection terminates forthwith [7]. The addi-
tion of newer antibacterials and antibiotics have negative conse-
quences in that, a fraction of bacteria can develop resistance to
the administered drug and escape to the human environment [8].
Intrinsically, drug resistance characters are exchanged among total
bacterial flora in the body as well as, in water/air environments
and are spread as multidrug-resistant (MDR) bacteria, both in hos-
pital and community settings [9–13]. From the use of antibiotics
of higher generations, the health domain is impacted gigantically;

https://doi.org/10.1016/j.molstruc.2021.131183
0022-2860/© 2021 Elsevier B.V. All rights reserved.
N.P. Mishra, S. Mohapatra, C.R. Sahoo et al.
consequently, structural modifications of obsolete drugs and intro-
duction of newer safer drugable molecules to pharmaceutics have
been the present trend for control, as examples seen often and
with other chemicals of curio [14]. Progressively evolving infec-
tions with MDR bacteria must be in control with an iron hand with
some eclectic approach(s). Thus it would be appropriated to ver-
ify 2H-chromene-based imidazo[1,2-a]pyridine derivatives as pep-
tide deformylase (PDF) inhibitors since these could be potent in
the control of human pathogenic bacteria [15].
Currently, bacterial PDF is a suitable target and has received at-
tention for its exploration as a ’possible novel antibiotic agent’ [16].
In bacterial cells, PDF is involved in the post-translational modifi-
cation of emerging polypeptides, and in this way, it removes the
formyl group of N-formyl methionine of the nascent protein to af-
ford a mature protein for use in bacterial protein synthesis [17]. In
mammalian cells, PDF was less active in comparison to its bacterial
counterpart, and also mammalian cytosolic protein synthesis does
not produce N-formylated polypeptides [18]. On the other hand,
PDF is a striking and unique target for treating resistant bacteria
as it produced the mature protein in bacterial cells [19].
From the last decade, various types of PDF inhibitors had been
developed by several pharmaceutical companies and academia
such as peptidic and pseudopeptidic analogs [20]. Among differ-
ent pseudopeptidic analogs “actinonin’’, a naturally occurring an-
tibiotic was reported as the first PDF inhibitor in 1962, which had a
modest antibacterial activity against both Gram-positive and Gram-
negative human pathogenic bacteria [17]. However, BB83698 and
LBM415 were the first two PDF inhibitors, which underwent hu-
man clinical trials [21,22]. The non-peptidic PDF inhibitors were
not much explored, as those are expected to be less suscepti-
ble to degradation [23]. By Merck research groups, biaryl acid
analogs were developed and evaluated as a PDF inhibitor against
the Gram-negative bacterium Escherichia coli PDF enzyme [24].
A report of β - sulfonyl and β -sulfinylhydroxamic acid deriva-
tives as PDF inhibitors against E. coli and another Gram-negative
Moraxella catarrhalis focused on the synthesis of various hetero-
cyclic compounds as PDF inhibitors had focused [25]. Further-
more, 5-Bromo-1H-indole-3-acetohydroxamic acid was reported by
another group as a PDF inhibitor [26]. The 2,5-dihydropyrrole
formyl hydroxyamino derivatives were also reported as PDF in-
hibitors [23]. Furthermore, benzofuran-4,5-diones was developed
as non-hydroxamic acid and non-peptidomimetic PDF inhibitor
[27]. Concomitantly, the antibacterial activities of oxazolidine LBM-
415 analogs as PDF inhibitors were reported [28]. A promising
target formyl hydroxyamino derivatives as a potent PDF inhibitor
against drug-resistant bacteria were also developed [29]. Con-
sequently, biphenyl tetrazole-thiazolidinediones were regarded as
novel bacterial PDF inhibitors [30].
As per the literature survey, it was found that there are
different drug molecules used as PDF inhibitors that contain
O/S/N-heterocycles as the core structure; nevertheless, nitrogen-
containing imidazopyridine being an important heterocycle are not
explored yet as PDF inhibitors. Indeed, imidazopyridine is a bio-
logically active compound and exhibits a wide range of biologi-
cal activities such as antibacterial, antifungal, antiviral, antitumor,
and anti-inflammatory activities [31–35]. Other than this, the natu-
rally occurring small pharmacophore 2H-chromene and its deriva-
tives are also known to possess a large spectrum of activities such
as antiallergic, antitumor, antiviral, antioxidant, anti-inflammatory,
antibacterial, and anticancer [36–43]. The high lipophilicity of 2H-
chromene derivatives allows a better cell permeability across the
bacterial cell membrane [44].
Furthermore, some imidazo[1,2-a]pyridine derivatives and
chromene derivatives have shown potent antibacterial activities
which are shown (Fig 1) [45–51]. In present circumstances, hybrid
molecules get more attention as these show more potencies than
2
Journal of Molecular Structure 1246 (2021) 131183
the concerned parent compound. Encouraged by the remark-
able antibacterial properties of both the pharmacophores, some
2H-chromene and imidazo[1,2-a]pyridine derivatives as hybrid
molecules and planned and were designed for study the antibac-
terial activity against the bacteria S. aureus, Streptococcus pyogenes
and E. coli, Klebsiella oxytoca isolated from clinical samples of
patients in Sum hospital, as sizes of zones of inhibition seen in
agar-well diffusion method in vitro, along with the determina-
tion of minimum inhibitory concentration (MIC) values of the
compounds.
2. Result and discussion
2.1. Chemistry
The 2H-chromene-3-carbaldehyde derivatives 11(a–i) and 2-
phenyl-2H-chromene-3-carbaldehyde derivatives 11’(a–h) had been
used as the starting materials. Initially, the 2H-chromene-3-
carbaldehydes 11(a–i) were synthesized by the reaction of sali-
cylaldehydes 9 with acrolein 10 using K2 CO3 in dioxane under
a reflux condition for 2h to afford 2H-chromene-3-carbaldehyde
derivatives 11(a–i) in good to excellent yields. On the other hand,
the 2-phenyl-2H-chromene-3-carbaldehydes 11’(a–h) were synthe-
sized by following oxa-Michael aldol reaction of salicylaldehydes 9
with cinnamaldehyde 10’ in the presence of pyrrolidine in DMSO
at a room temperature for 12 h with a good to excellent yields
(Scheme 1) [52–54].
After the successful synthesis of starting materials, 2H-
chromene-3-carbaldehydes 11(a–i) and 2-phenyl-2H-chromene-3-
carbaldehydes 11’(a–h), the synthesis of the 2H-chromene based
imidazo[1,2-a] pyridine derivatives 13(a–q) via, one-pot aza-Henry
reaction was explored. The individual reactions of substituted 2H-
chromene aldehydes 11(a–i) and 11’(a–h) with 2-aminopyridine 12
and nitromethane in the presence of different catalysts and sol-
vents to establish the feasibility of the strategy and to optimize
the reaction conditions were pursued. Initially, the reaction was
studied in the conventional heating at 40 to 120 °C for 4 to 6 h,
but the desired product was not obtained. Later on, the same re-
action in the ‘microwave irradiation method’ at 40 to 120 °C in
30–60W by varying catalyst loading and solvents was carried out.
However, the reaction of 2H-chromene-3-carbaldehydes 11a and 2-
amino pyridine 12 in the presence of catalyst FeCl3 (10 mol%) in
DMF and nitromethane binary solvent system at 40 °C and 30W in
10 min, no product was formed. Again the reaction was tried at a
slightly higher temperature i.e., 80 °C in a similar reaction condi-
tion which provided slightly better yield (45%) of the product [55].
We studied the reaction in different solvents, the CH3 CN, toluene,
THF, and DMSO (entries1–5, Table 1); but those attempts provided
poor yields of products in comparison with, the use of a mixture
of nitromethane and DMF (entry 6, Table 1). After the standard-
ization of solvent, further, the reaction by increasing the temper-
ature, power, and time were studied. It was noticed that increase
in temperature, microwave power, and time increased the yield of
the reaction; while better effectiveness was achieved with an ex-
cellent yield up to 88% when the reaction proceeded at 100 °C and
60W for 15 min in the presence of FeCl3 (30 mol%); thus, an excel-
lent yield of product was obtained (entry 10, Table 1). Furthermore,
an increase in temperature, the yield was decreased (entry 11–12,
Table 1). Moreover, when the reaction was carried out in a neat
condition without any solvent, comparatively a very poor yield
of the target product had resulted. However, the common Lewis
acids like, AlCl3 , ZnCl2 and CuCl were not effective for this reaction
(entry 15–17, Table 1). The optimal reaction conditions were ob-
tained using 2H-chromene-3-carbaldehydes 11a and 2-amino pyri-
dine 12, in the presence of the catalyst FeCl3 (30 mol%) in DMF
and nitromethane binary solvent system at 100 °C, with 60W in
N.P. Mishra, S. Mohapatra, C.R. Sahoo et al. Journal of Molecular Structure 1246 (2021) 131183

Fig 1. Imidazopyridine (1–6), 2H-chromene based antibacterial agents (7,8), and designed 2H-chromene based imidazo[1,2-a]pyridine derivatives as synthetic targets.

Table 1
Optimization of the reaction conditionsa .

Entry Catalyst(mol%) Solvent Temp(°C) Watt Time(min) yieldb

1 FeCl3 (10%) DMF 40 30 10 n.r

2 FeCl3 (10%) DMF 80 30 10 45%
3 FeCl3 (10%) Toluene 80 30 10 20%
4 FeCl3 (10%) CH3 CN 80 30 10 34%
5 FeCl3 (10%) THF 80 30 10 16%
6 FeCl3 (10%) DMSO 80 30 10 28%
7 FeCl3 (10%) DMF 90 30 10 55%
8 FeCl3 (20%) DMF 90 60 10 63%
9 FeCl3 (30%) DMF 90 60 15 69%
10 FeCl3 (30%) DMF 100 60 15 88%
11 FeCl3 (30%) DMF 110 60 15 74%
12 FeCl3 (30%) DMF 120 60 20 62%
13 FeCl3 (30%) - 100 60 15 14%
14 FeCl3 (30%) - 110 60 20 19%
15 AlCl3 (30%) DMF 100 60 15 5%
16 ZnCl3 (30%) DMF 100 60 15 10%
17 CuCl(30%) DMF 100 60 15 7%
18 - DMF 100 60 15 n.r
a
Reaction conditions: Substituted 2H-chromene aldehydes (1.0 mmol), 2-
aminopyridine (1.2 mmol), FeCl3 (0.3 mmol) in a mixture of nitroalkane and
DMF (1:1) at 100°C in 60W for 15min.
b
Isolated yields, obtained by column chromatography.

15min. The completion of the reaction was monitored by TLC and
the reaction mixture was extracted with a mixture of ethyl ac-
etate and water. The organic layer was separated and was made
to dry over anhydrous Na2 SO4; further, the products were evapo-
rated under reduced pressure. The crude reaction mixture was pu-
rified by column chromatography. The structures of 2H-chromene-
based imidazo[1,2-a]pyridine derivatives 13a were established by
1 H NMR, 13 C NMR, and mass spectroscopy.
With the optimized reaction conditions in hand, to broaden the
scope of this protocol, the reaction by varying substituents were
tried in 2H-chromene-3-carbaldehydes 11(a–i) and 2-phenyl-2H-
chromene-3-carbaldehydes 11’(a–h) separately (Scheme 2). Both
electron-rich and electron-deficient substituents on 2H-chromene-
3-carbaldehydes reacted efficiently with 2-aminopyridine to afford
the desired products 13(a–q) with comparatively good to excel-
lent yields. The methoxy and ethoxy groups on 2H-chromene-
3-carbaldehydes and 2-phenyl-2H-chromene-3-carbaldehydes gave
the corresponding products, namely 13(b–d), and 13(k–n) in good
to high yields (80–86%). Slightly decrease in the yield at 73-
78% was noticed when halogenated and naphthyl 2H-chromene-

3
N.P. Mishra, S. Mohapatra, C.R. Sahoo et al.
Scheme 1. Synthesis of 2H-chromene-3-carbaldehydes 11(a–i) and 2-Phenyl-2H-
chromene-3- carbaldehydes 11’(a–h).
3-carbaldehydes and 2-phenyl-2H-chromene-3-carbaldehydes were
used as a starting material. However, in proceeding with the re-
action with simple 2-phenyl-2H-chromene-3-carbaldehydes 11’a, a
better yield (87%) of 13j was obtained. Structures of the synthe-
sized compounds, 13(a–q) were confirmed by 1 H NMR, 13 C NMR,
and mass spectroscopy (Table 2).
The probable mechanism of the reaction is presented in
Scheme 3. as, the reaction of 2-aminopyridine 12 and chromene
aldehyde 11 forms imine A, which underwent aza-Henry reaction
by CH3 NO2 and FeCl3 to produce intermediate B. Thereafter, tau-
tomerization of the intermediate B gave intermediate C, which un-
derwent an intramolecular cyclization to give intermediate D. Fi-
nally, the 2H-chromene based imidazo[1,2-a]pyridine derivative 13
was resulted by the subsequent eliminations of both water and
HNO [55].
2.2. Biological evaluation
2.2.1. Antibacterial study
The binding affinity of the synthesized compounds 13(a–q) was
studied in silico with PDF. The results suggested that the com-
pounds 13e, 13g, 13h, 13i, and 13n with good binding affinity val-
ues as docking scores of 8.1 kCal/mol, -8.3 kCal/mol, -8.2 kCal/mol,
-8.7 kCal/mol, and -8.3 kCal/mol, respectively in case of E. coli;
while in case of S. aureus, docking scores of -6.6, -7.9, -7.8, -
Scheme 2. Synthesis of 2H-chromene based imidazo[1,2-a]pyridine derivatives 13(a–q)
4
Journal of Molecular Structure 1246 (2021) 131183
8.0 and,-8.0 kCal/mol were noted. Furthermore, we have stud-
ied the antibacterial activity of all synthesized compounds 13(a-q)
against Gram-ve and Gram+ve bacterium and antibacterial results
revealed that these compounds were active against E. coli, K. oxy-
toca, S. aureus, and S. pyogenes (Table 3). Among all, compounds
13e, 13g, 13h, 13i, and 13n had better antibacterial activity. Partic-
ularly, the compound 13i was potentially active against E. coli, with
18 mm, as the zone of inhibition in the agar well diffusion method,
and 16 μg/mL was the MIC value, comparable to that of the stan-
dard drug Ciprofloxacin MIC value 28 μg/mL for each. Indeed, the
compounds containing the naphthyl group had significant antibac-
terial activity [56,57].
2.2.2. Structure-activity relationships (SAR studies)
In compounds, 13o, 13p, 13q, 13k,13l and 13m (2-phenyl
chromene based imidazo[1,2-a]pyridine) in presence of halogens
and methoxy group in different positions of the benzene ring of
benzopyran had less binding interactions with peptide deformy-
lase of both Gram-negative and Gram-positive bacteria like E. coli
and S. aureus; but the presence of the ethoxy group in 13n caused
increased binding interactions, so that 13n had a better antibac-
terial activity towards both human pathogens E. coli and S. au-
reus with MIC values, 20 and 24 μg/mL, respectively. Surprisingly,
in compounds, 13e, 13g, 13h, and 13i the phenyl group is absent
in the 2-position of benzopyran), but with the presence of halo-
gens and naphthyl substituents in different positions of the ben-
zene ring of benzopyran had a comparatively more binding inter-
action with peptide deformylase of both Gram-negative and Gram-
positive bacteria such as E. coli and S. aureus. Moreover, the pres-
ence of methoxy and bromo groups in the benzene ring of ben-
zopyran showed comparatively a lesser binding interaction with
the peptide deformylase. Compounds 13e, 13g, 13h, and 13i, how-
ever, had better antibacterial activities towards both E. coli and S.
aureus with higher MIC values. But at the naphthyl group at 5, 6
positions of the benzene ring of 2H-chromene having imidazo[1,2-
a]pyridine, the 13i caused a higher antibacterial activity against E.
coli, and with the MIC value 16 μg/mL.
2.3. Computational studies
To comprehend the mechanism of inhibition PDF enzyme,
molecular docking studies were performed between the newly
synthesized 2H-chromene based imidazo[1,2-α ]pyridine deriva-
tives, 13(a–q), against the PDF enzyme of E. coli (PDBID:1DFF), as
well as, of S. aureus (PDBID:1LMH) [58]. The molecular docking
studies signified the binding modes of action and the structural
optimizations of the synthesized compounds. The docking scores
of the newly synthesized compounds, 13(a–q) ranged from, -7.3
to -8.7 kCal/mol in the case of E. coli (PDBID:1DFF), and -6.2 to
-8.0 kCal/mol in the case of S. aureus (PDBID:1LMH). The docking
N.P. Mishra, S. Mohapatra, C.R. Sahoo et al. Journal of Molecular Structure 1246 (2021) 131183

Table 2
Substrate scope for the synthesis of 2H-chromene based imidazo[1,2-α ]pyridine deriva-
tives 13(a–q) by the microwave method.

Serial no Compound Time (min) Yield(%)

1 15 88

2 15 85

3 15 84

4 15 82

5 15 78

6 15 77

7 15 73

8 15 75

(continued on next page)

5
N.P. Mishra, S. Mohapatra, C.R. Sahoo et al. Journal of Molecular Structure 1246 (2021) 131183

Table 2 (continued)

Serial no Compound Time (min) Yield(%)

9 15 74

10 15 87

11 15 86

12 15 85

13 15 83

14 15 80

15 15 79

(continued on next page)

6
N.P. Mishra, S. Mohapatra, C.R. Sahoo et al.
Table 2 (continued)
Serial no Compound
16
17
Scheme 3. Proposed reaction mechanism of 2H-chromene based imidazo[1,2-a]pyridine.
scores and binding interactions are presented (SI-Table 1). Found
from docking studies of compounds 13e, 13g, 13h, 13i, and 13n
that those possess some higher negative docking score values, viz.,
-8.1 kCal/mol, -8.3 kCal/mol, -8.2 kCal/mol, -8.7 kCal/mol, and -
8.3 kCal/mol, respectively in case of E. coli; while, in case of S.
aureus, docking scores were lesser, -6.6 kCal/mol, -7.9 kCal/mol,
-7.8 kCal/mol, -8.0 kCal/mol and,-8.0 kCal/mol for the respective
five compounds, in succession. The binding energy values of all
compounds signify that compounds were held in the active pocket
of PDF of the target bacteria, E. coli, and S. aureus. The inter-
actions of compounds with PDF occur through hydrogen bond-
ing, alkyl, π -π interaction, π - donor hydrogen bonding and π -σ
7
Journal of Molecular Structure 1246 (2021) 131183
Time (min) Yield(%)
15 77
15 72
interactions. The binding interaction of the most active PDF in-
hibitor 13i is presented (Fig 2). The compound 13i held into the
active pockets of PDF enzymes of both E. coli and S. aureus formed
several hydrophobic and Van der Waals interactions with amino
acid residues, such as His132, Cys129, Ile44, Gly89, Arg97, Leu91of
E. coli, with Glu185, Val59, His154, Val151 of S. aureus, respec-
tively with binding score -8.7 kCal/mol and -8.0 kCal/mol (Table 4).
From the 3D-interaction of the synthesized 2H-chromene-based
imidazo[1,2-α ]pyridine derivatives; it was found that the com-
pound 13i containing the naphthyl group was important for the
PDF-inhibitibitory activity and consequently possesses a potent an-
tibacterial activity.
N.P. Mishra, S. Mohapatra, C.R. Sahoo et al. Journal of Molecular Structure 1246 (2021) 131183

Fig. 2. Structure-activity relationship of chromene based imidazopyridines.

Fig. 3. Docking study of compound 13i with E. coli and binding interaction with PDF (PDBID:1DFF).

8
N.P. Mishra, S. Mohapatra, C.R. Sahoo et al. Journal of Molecular Structure 1246 (2021) 131183

Table 3
Antimicrobial activities of synthesized 2H-chromene based imidazo[1,2-a]pyridine derivatives.

Compound E. coli K. oxytoca S. aureus S. pyogenes

name
ZI (mm) MIC (μg/mL) ZI (mm) MIC (μg/mL) ZI (mm) MIC (μg/mL) ZI (mm) MIC (μg/mL)

13a 12 36 12 36 13 32 13 36
13b 13 32 12 36 13 32 13 36
13c 12 36 13 36 12 36 14 32
13d 14 28 13 36 13 36 13 32
13e 16 24 14 32 15 24 14 28
13f 14 28 13 36 13 32 13 32
13g 17 20 14 32 17 20 15 28
13h 16 24 14 28 16 24 14 24
13i 18 16 15 24 17 20 16 28
13j 14 28 12 32 14 28 13 32
13k 13 28 11 36 13 32 12 32
13l 14 24 12 36 13 32 12 36
13m 13 28 11 36 13 32 13 32
13n 17 20 15 28 16 24 14 28
13o 14 28 11 36 12 32 13 32
13p 13 32 11 36 12 32 13 32
13q 13 32 11 36 12 32 13 32
Std 17 28 18 24 28 28 18 20

ZI: Zone of inhibition; MIC: minimum inhibitory concentration; Std: Standard, Ciprofloxacin.

Fig. 4. Docking study of compound 13i with S. aureus and binding interaction with PDF (PDBID:1LMH).

Table 4
Docking score (kCal/mol) and binding interactions of compound 13i with peptide deformylase.

Testedcompound Docking score (kCal/mol) and binding interactions with peptide deformylase

E. coli (PDBID:1DFF) S. aureus (PDBID:1LMH)

13i -8.7 -8.0
HIS132, CYS129, ILE44, GLY89, ARG97, LEU91 GLU185, VAL59, HIS154, VAL151

3. Conclusion ghoulish bacterial pathogens, S. aureus, S. pyogenes, E. coli, and K.

Herein, a simple and novel one-pot, microwave-assisted syn-
thesis of 2H-chromene based imidazo[1,2-a]pyridines are reported,
and evaluated for antibacterial activities along with the MIC values
of the compounds, against human pathogenic representative two
Gram-positive and Gram-negative bacteria. The results indicated
that these selected during the synthesis of these compounds could
be suggested as potent compounds with antibacterial potency for
two reasons namely, (1) molecular docking results of these com-
pounds and PDF individually landed at encouraging docking score
results, (2) the in vitro antibacterial screening by agar-well diffu-
sion method followed by MIC assay had too encouraging outcomes.
Thus, it would not be out of place to state that the clinical frater-
nity is in search of such novel synthetic potent molecules for the
oxytoca as used in vitro for this study. Moreover, the compounds
13e, 13g, 13h, 13i, and 13n could be suggested for further studies
in pharmacological drug development attempts.
4. Experimental
4.1. Instrumentation
All reagents and solvents were purchased from commercial sup-
pliers. 2-aminopyridine, nitromethane, FeCl3 , and all solvents were
purchased from Sigma-Aldrich. Substituted 2H-chromene aldehy-
des were synthesized in the laboratory. Progress of the reaction
was monitored by TLC on silica gel 60 F254 -coated TLC plates
(Merck KGaA, Darmstadt, Germany) and was visualized by Short-

9
N.P. Mishra, S. Mohapatra, C.R. Sahoo et al.
UV light at 254 nm. The proton nuclear magnetic resonance (1 H
and 13 C NMR) spectra were recorded on a JEOL 400 MHz NMR
spectrometer. Chemical shifts (δ ) are reported in parts per million,
downfield from the internal standard (TMS, δ = 0.00 ppm) rela-
tive to residual CDCl3 (1 H: δ = 7.26 ppm, 13 C: δ = 77.00 ppm)
as an internal reference. Coupling constants (J) were reported in
Hertz (Hz). Peak multiplicity was indicated as follows: s-singlet, d-
doublet, t-triplet, q-quartet, m-multiplet, and dd-doublet of a dou-
blet. Melting points were recorded with an electrothermal digi-
tal melting point apparatus measured on a Stuart SPM10 melt-
ing point instrument. High-resolution mass spectra (HRMS) were
recorded at IIT, Madras as well as, NISER, Bhubaneswar. CHN anal-
ysis were recorded at central laboratory-OUAT, Bhubaneswar. The
final product was synthesized using a CEM microwave synthesizer
(model No-908010).
4.2. General procedure for the synthesis of compound 13(a–q)
A mixture of substituted 2H-chromene aldehydes(1.0mmol), 2-
aminopyridine (1.2 mmol), and FeCl3 (0.3mmol) in a mixture of ni-
troalkane and DMF (1:1) was taken in a clean dry microwave tube
and was placed under microwave irradiation at 60W,100 °C for
15 min. The progress of the reaction was monitored by TLC. Af-
ter completion of the reaction, the reaction mixture was diluted
with ethyl acetate and the product was extracted with water. The
organic layer was separated, dried over anhydrous Na2 SO4, and
evaporated under reduced pressure. The crude reaction mixture
was purified by column chromatography to furnish the desired 2H-
chromene based imidazo[1,2-a]pyridines 13(a–q) with good to high
yield (72–88%).
4.2.1. 4.2.1.2-(2H-chromen-3-yl)imidazo[1,2-a]pyridine(13a)
Brown solid; m.p. 198–200 °C; 1 H NMR(400 MHz, CDCl3 , δ
ppm) δ 5.20 (s, 2H), 6.76–6.79 (m, 1H), 6.85 (d, 1H, J = 8Hz),
6.91–6.94 (m, 1H), 7.12–7.13 (m, 2H), 7.15–7.21 (m, 1H), 7.27 (s,
1H), 7.59–7.60 (m, 2H), 8.08 (d, 1H, J = 6.8 Hz); 13 C NMR (100
MHz, CDCl3 , δ ppm): 66.1, 108.4, 112.5, 115.5, 117.3, 120.1, 121.6,
122.8, 125.3, 125.6, 127.2, 129.0, 142.2, 145.7, 153.6 . ESI-HRMS:
m/z [M + H]+ calcd for C16 H12 N2 O: 249.0950; found: 249.0872.
Calcd%: C, 77.40; H, 4.87; N, 11.28; Found% C, 77.38; H, 4.85; N,
11.25.
4.2.2.
4.2.2.2-(6-methoxy-2H-chromen-3-yl)imidazo[1,2-a]pyridine(13b)
Brick red solid; m.p. 196-201 °C; 1 H NMR(400 MHz, CDCl3 , δ
ppm) δ 3.78 (s, 3H), 5.14 (s, 2H), 6.68–6.70 (m, 2H), 6.78–6.81 (m,
2H), 7.17–7.21 (m, 1H), 7.24–7.26 (m, 1H), 7.57–7.60 (m, 2H), 8.08
(d, J = 6.4 Hz, 1H); 13 C NMR (100 MHz, CDCl3 , δ ppm): 55.7, 66.1,
108.6, 112.2, 112.5, 114.0, 116.0, 117.3, 120.2, 123.6, 125.4, 125.6,
126.6, 142.1, 145.7, 147.6, 154.3. ESI-HRMS: m/z [M + H]+ calcd for
C17 H14 N2 O2 : 279.1055; found:279.1262. Calcd%: C, 73.37; H, 5.07;
N, 10.07; Found% C, 73.33; H, 5.06; N, 10.05.
4.2.3.
4.2.3.2-(7-methoxy-2H-chromen-3-yl)imidazo[1,2-a]pyridine(13c)
Deep brown solid; m.p. 194-198 °C, 1 H NMR(400 MHz, CDCl3 ,
δ ppm) δ 3.79 (s, 3H), 5.17 (s, 2H), 6.45–6.49 (m, 2H), 6.75–6.77
(m, 1H), 7.03 (d, J = 7.6 Hz, 1H), 7.16–7.22 (m, 2H), 7.55–7.59 (m,
2H), 8.07 (d, J = 6.8 Hz, 1H); 13 C NMR (100 MHz, CDCl3 , δ ppm):
55.4, 66.2, 101.5, 107.4, 107.9, 112.4, 116.0, 117.1, 120.0, 122.5, 125.2,
125.5, 127.9, 142.5, 145.6, 154.9, 160.7. ESI-HRMS: m/z [M + H]+
calcd for C17 H14 N2 O2 : 279.1055; found:279.1113. Calcd%: C, 73.37;
H, 5.07; N, 10.07; Found% C, 73.36; H, 5.06; N, 10.07.
10
Journal of Molecular Structure 1246 (2021) 131183
4.2.4.
4.2.4.2-(8-ethoxy-2H-chromen-3-yl)imidazo[1,2-a]pyridine(13d)
Brick red solid; m.p. 197–199 °C,1 H NMR(400 MHz, CDCl3 , δ
ppm) δ 1.47 (t, J = 6.8 Hz, 3H), 4.13 (q, J = 6.8 Hz, 2H), 5.24 (s,
2H), 6.77–6.87 (m, 4H), 7.16–7.20 (m, 1H), 7.27 (s, 1H), 7.58–7.60
(m, 2H), 8.08 (d, J = 6.8 Hz, 1H); 13 C NMR (100 MHz, CDCl3 , δ
ppm): 14.9, 64.5, 66.2, 108.5, 112.5, 113.5, 117.3, 119.6, 120.1, 121.2,
124.6, 125.3, 125.5, 125.6, 142.1, 142.7, 145.7, 146.8. ESI-HRMS:
m/z [M + H]+ calcd for C18 H16 N2 O2 : 293.1212; found: 293.1286.
Calcd%:C, 73.95; H, 5.52; N, 9.58; Found% C, 73.94; H, 5.50; N, 9.58.
4.2.5.
4.2.5.2-(6-chloro-2H-chromen-3-yl)imidazo[1,2-a]pyridine(13e)
Brown solid; m.p. 204–208 °C; 1 H NMR(400 MHz, CDCl3 , δ
ppm) 5.21 (s, 2H), 6.77–6.81 (m, 2H), 7.05-7.08 (s, 2H), 7.19–7.23
(m, 2H), 7.58–7.62 (m, 2H), 8.09 (d, J = 7.2 Hz, 1H); 13 C NMR
(100 MHz, CDCl3 , δ ppm): 66.2, 108.8,112.7, 116.8, 117.4, 118.9,
124.2, 125.5, 125.6, 126.3, 126.5, 126.9, 128.5, 141.7, 145.8, 152.1.
ESI-HRMS: m/z [M + H]+ calcd for C16 H11 ClN2 O: 283.0560; found:
283.0634. Calcd%: C, 67.97; H, 3.92; N, 9.91; Found% C, 67.95; H,
3.91; N, 9.90.
4.2.6.
4.2.6.2-(6-bromo-2H-chromen-3-yl)imidazo[1,2-a]pyridine(13f)
Brown solid; m.p. 207–209 °C; 1 H NMR (400 MHz, CDCl3 , δ
ppm) 5.20 (s, 2H), 6.73 (d, J = 7.6 Hz, 1H), 6.78–6.81 (m, 1H), 7.17–
7.26 (m, 4H),7.58–7.61 (m, 2H), 8.08 (d, J = 6.4 Hz, 1H); 13 C NMR
(100 MHz, CDCl3 , δ ppm): 66.2, 108.8, 112.7, 113.6, 117.2, 117.4,
118.7, 124.7, 125.5, 125.6, 126.8, 129.3, 131.4, 141.7, 145.7, 152.6.
ESI-HRMS: m/z [M + H]+ calcd for C16 H11 BrN2 O: 327.0055; found:
327.0131. Calcd%: C, 58.74; H, 3.39; N, 8.56; Found% C, 58.71; H,
3.36; N, 8.55.
4.2.7.
4.2.7.2-(6,8-dibromo-2H-chromen-3-yl)imidazo[1,2-a]pyridine
(13g)
Deep red solid; m.p. 211–213 °C; 1 H NMR(400 MHz, CDCl3 , δ
ppm) 5.32 (s, 2H), 6.79–6.82 (m, 1H), 7.16 (d, J = 2.4 Hz, 1H), 7.17–
7.18 (m, 1H), 7.20-7.24 (m, 1H), 7.46 (d, J = 2.0 Hz, 1H), 7.58–7.61
(m, 2H), 8.09–8.11 (m, 1H); 13 C NMR (100 MHz, CDCl3 , δ ppm):
66.9, 109.0, 110.3, 112.8, 113.5, 117.5, 118.2, 125.5, 125.7, 125.8,
127.4, 128.6, 134.0, 141.1, 145.8, 149.5. ESI-HRMS: m/z [M + H]+
calcd for C16 H10 Br2 N2 O: 406.9139; found: 406.9210. Calcd%: C,
47.33; H, 2.48; N, 6.90; Found% C, 47.30; H, 2.46; N, 6.88.
4.2.8.
4.2.8.2-(6,8-dichloro-2H-chromen-3-yl)imidazo[1,2-a]pyridine(13h)
Brown solid; m.p. 207–208 °C; 1 H NMR (400 MHz, CDCl3 , δ
ppm) 5.30 (s, 2H), 6.79–6.83 (m, 1H), 6.99 (d, J =2Hz, 1H), 7.16–7.19
(m, 2H), 7.22–7.24 (m, 1H), 7.59–7.61 (m, 2H), 8.10 (d, J = 7.2 Hz,
1H); 13 C NMR (100 MHz, CDCl3 , δ ppm): 66.7, 109.0, 112.8, 117.4,
118.2, 121.2, 125.0, 125.6, 125.7, 126.1, 127.4, 128.6, 141.0, 145.8,
147.9. ESI-HRMS: m/z [M + H]+ calcd for C16 H10 Cl2 N2 O: 317.0170;
found: 317.0257. Calcd%: C, 60.59; H, 3.18; N, 8.83; Found% C,
60.58; H, 3.15; N, 8.82.
4.2.9.
4.2.9.2-(3H-benzo[f]chromen-2-yl)imidazo[1,2-a]pyridine(13i)
Brown solid; m.p. 209–211 °C; 1 H NMR (400 MHz, CDCl3 , δ
ppm) 5.27 (s, 2H), 6.80-6.83 (m, 1H), 7.14 (d, J = 8.8 Hz, 1H),
7.19–7.23 (m, 1H), 7.36–7.39 (m, 1H), 7.49-7.53 (m, 1H), 7.63–7.68
(m, 3H), 7.76 (d, J = 8.4 Hz, 1H), 7.99 (s, 1H), 8.11 (d, J = 6.4
Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H); 13 C NMR (100 MHz, CDCl3 , δ
ppm): 66.1, 108.6, 112.5, 116.0, 116.4, 117.3, 117.3, 121.9,123.8, 123.9,
125.4, 125.6, 126.6,128.5,129.3, 129.6, 130.2, 142.6, 145.8, 152.0.
ESI-HRMS: m/z [M + H]+ calcd for C20 H14 N2 O: 299.1106; found:
N.P. Mishra, S. Mohapatra, C.R. Sahoo et al.
299.1178. Calcd%: C, 80.52; H, 4.73; N, 9.39; Found% C, 80.50; H,
4.70; N, 9.38 .
4.2.10.
4.2.10.2-(2-phenyl-2H-chromen-3-yl)imidazo[1,2-a]pyridine(13j)
Brown solid; m.p. 198-200 °C; 1 H NMR (400 MHz, CDCl3 , δ
ppm) 6.31 (s, 1H), 6.69-6.72 (m, 1H), 6.76 (d, J = 8 Hz,1H), 6.86–
6.90 (m, 1H), 7.05–7.09 (m, 1H), 7.14-7.21 (m, 2H), 7.25–7.30 (m,
4H), 7.49–7.50 (m, 2H), 7.56 (d, J = 9.2 Hz, 1H), 7.65 (s, 1H), 7.92
(d, J = 6.4 Hz, 1H); 13 C NMR (100 MHz, CDCl3 , δ ppm): 77.3, 109.2,
112.3, 116.3, 117.2, 120.9, 121.4, 122.4, 125.3, 125.6, 126.9, 127.1,
127.9, 128.6, 128.7, 129.3, 138.8, 142.6, 145.5, 151.7. ESI-HRMS: m/z
[M + H]+ calcd for C22 H16 N2 O: 325.1263; found: 325.1339. Calcd%:
C, 81.46; H, 4.97; N, 8.64; Found% C, 81.44; H,4.95; N, 8.61.
4.2.11. 4.2.11.2-(8-methoxy-2-phenyl-2H-chromen-3-yl)imidazo[1,2-
a]pyridine(13k)
Brown solid; m.p. 198–201o C; 1 H NMR (400 MHz, CDCl3 , δ
ppm) 3.78 (s, 3H), 6.38 (s, 1H), 6.71–6.75 (m, 2H), 6.81–6.85 (m,
2H), 7.13–7.17 (m, 1H), 7.24–7.28 (m, 3H), 7.35 (s, 1H), 7.53-7.58
(m, 3H), 7.65 (s, 1H), 7.95 (d, J = 7.2 Hz, 1H); 13 C NMR (100
MHz, CDCl3 , δ ppm): 56.4, 76.8, 109.4, 112.4, 112.8, 117.3, 119.7,
120.9, 121.2, 123.4, 125.5, 125.7, 127.2, 128.0, 128.6, 128.7, 138.8,
140.8, 142.7, 145.7, 148.3. ESI-HRMS: m/z [M + H]+ calcd for
C23 H18 N2 O2 : 355.1368; found: 355.1420. Calcd%: C, 77.95; H, 5.12;
N, 7.90; Found% C, 77.90; H, 5.06; N, 7.85.
4.2.12. 4.2.12.2-(6-methoxy-2-phenyl-2H-chromen-3-
yl)imidazo[1,2-a]pyridine(13l)
Brown solid; m.p. 197–199o C; 1 H NMR (400 MHz, CDCl3 , δ
ppm) 3.76 (s, 3H), 6.25 (s, 1H), 6.61–6.65 (m, 1H), 6.68–6.73 (m,
2H), 6.76 (d, J = 2.8 Hz, 1H), 7.13–7.17 (m, 1H), 7.24–7.29 (m, 3H),
7.33 (s, 1H), 7.47–7.49 (m, 2H), 7.56 (d, J = 9.2 Hz, 1H), 7.62(s,
1H), 7.94 (d, J = 6.0 Hz, 1H); 13 C NMR (100 MHz, CDCl3 , δ ppm):
55.6, 76.7, 109.3, 112.0, 112.3, 114.5, 116.9, 117.2, 121.0, 123.2, 125.4,
125.6, 127.8, 127.9, 128.5, 128.6, 138.6, 142.6, 145.5, 145.6, 154.1.
ESI-HRMS: m/z [M + H]+ calcd for C23 H18 N2 O2 : 355.1368; found:
355.1457. Calcd%: C, 77.95; H, 5.12; N, 7.90; Found% C, 77.92; H,
5.11; N, 7.88.
4.2.13. 4.2.13.2-(7-methoxy-2-phenyl-2H-chromen-3-
yl)imidazo[1,2-a]pyridine(13m)
Brown solid; m.p. 196–198 °C; 1 H NMR (400 MHz, CDCl3 , δ
ppm) 3.73 (s, 3H), 6.28 (s, 1H), 6.35 (d, J = 2.4 Hz, 1H), 6.45
(dd, J = 2.4 Hz, J = 8.0 Hz, 1H), 6.69 (t, J = 7.2 Hz, 1H), 7.10–
7.15 (m, 2H), 7.27–7.29 (m, 4H), 7.49–7.56 (m, 3H), 7.61 (s, 1H),
7.93 (d, J = 6.8 Hz, 1H); 13 C NMR (100 MHz, CDCl3 , δ ppm):
55.3, 76.7, 102.1, 107.4, 108.7, 112.1, 115.7, 117.1, 120.7, 124.0, 125.2,
125.5, 127.8, 127.9, 128.6, 128.7, 138.9, 142.9, 145.5, 153.0, 160.9.
ESI-HRMS: m/z [M + H]+ calcd for C23 H18 N2 O2 : 355.1368; found:
355.1417. Calcd%: C, 77.95; H, 5.12; N, 7.90; Found% C, 77.93; H,
5.09; N, 7.88.
4.2.14. 4.2.14.2-(8-ethoxy-2-phenyl-2H-chromen-3-yl)imidazo[1,2-
a]pyridine(13n)
Brown solid; m.p. 199–201 °C; 1 H NMR (400 MHz, CDCl3 , δ
ppm) δ 1.32 (t, J = 6.8 Hz, 3H), 3.98 (q, J = 6.8 Hz, 2H), 6.37 (s, 1H),
6.70–6.75 (m, 2H), 6.79–6.86 (m, 2H), 7.14-7.18 (m, 1H), 7.24–7.25
(m, 3H), 7.36 (s, 1H), 7.53–7.58 (m, 3H), 7.65 (s, 1H), 7.96 (d, J = 6.8
Hz, 1H); 13 C NMR (100 MHz, CDCl3 , δ ppm): 14.8, 65.0, 76.7, 109.2,
112.3, 114.9, 117.2, 119.8, 120.9, 121.1, 123.7, 125.4, 125.6, 127.1,
127.9, 127.9, 128.4, 128.4, 128.5, 138.8, 141.4, 142.8, 145.6, 147.4.
ESI-HRMS: m/z [M + H]+ calcd for C24 H20 N2 O2 : 369.1525; found:
369.1601. Calcd%: C, 78.24; H, 5.47; N, 7.60; Found% C, 78.22; H,
5.45; N, 7.59.
11
Journal of Molecular Structure 1246 (2021) 131183
4.2.15. 4.2.15.2-(6-bromo-2-phenyl-2H-chromen-3-yl)imidazo[1,2-
a]pyridine(13o)
Brown solid; m.p. 195–197 °C; 1 H NMR (400 MHz, CDCl3 , δ
ppm) 6.31 (s, 1H), 6.64 (d, J = 8.4 Hz, 1H), 6.71-6.74 (m, 1H),
7.13–7.19 (m, 2H), 7.27–7.28 (m, 4H), 7.34 (s, 1H), 7.46–7.48 (m,
2H), 7.56–7.58 (m, 2H), 7.95 (d, J = 6.8 Hz, 1H); 13 C NMR (100
MHz, CDCl3 , δ ppm): 76.7, 109.6, 112.5, 113.5, 117.3, 118.1, 119.6,
124.5, 125.5, 125.6, 127.9, 127.9, 128.2, 128.7, 128.7, 128.9, 129.3,
131.8, 138.3, 142.1, 145.6, 150.8. ESI-HRMS: m/z [M+H]+ calcd
for C22 H15 BrN2 O: 403.0368; found: 403.0203. Calcd%: C, 65.52; H,
3.75; N, 6.95; Found% C, 65.50; H, 3.72; N, 6.94.
4.2.16. 4.2.16.2-(6-chloro-2-phenyl-2H-chromen-3-yl)imidazo[1,2-
a]pyridine(13p)
Brown solid; m.p. 197-199o C; 1 H NMR(400 MHz, CDCl3 , δ ppm)
6.31 (s, 1H), 6.68-6.74 (m, 2H), 7.01 (dd, J = 2.8 Hz, J = 8.8 Hz,
1H), 7.15–7.19 (m, 2H), 7.27–7.29 (m, 3H), 7.34 (s, 1H), 7.45–7.49
(m, 2H), 7.56–7.58 (m, 2H), 7.95 (d, J = 6.8 Hz, 1H); 13 C NMR (100
MHz, CDCl3 , δ ppm): 76.7, 109.6, 112.4, 117.3, 117.7, 119.7, 123.9,
125.5, 125.6, 126.1, 126.4, 127.9, 127.9, 128.3, 128.7, 128.8, 128.8,
128.9, 138.3, 142.1, 145.5, 150.2. ESI-HRMS: m/z [M + H]+ calcd
for C22 H15 ClN2 O: 359.0873; found: 359.0979. Calcd%: C, 73.64; H,
4.21; N, 7.81; Found% C, 73.61; H, 4.19; N, 7.79.
4.2.17. 4.2.17.2-(8-bromo-6-chloro-2-phenyl-2H-chromen-3-
yl)imidazo[1,2-a]pyridine(13q)
Brown solid; m.p. 201–204 °C; 1 H NMR (400 MHz, CDCl3 , δ
ppm) 6.45 (s, 1H), 6.74–6.77 (m, 1H), 7.09 (d, J= 2 Hz,1H), 7.18–7.22
(m, 2H),7.27–7.28 (m, 3H), 7.41 (s, 1H), 7.49–7.51 (m, 2H), 7.55 (s,
1H), 7.59 (d, J = 9.2 Hz, 1H), 7.98 (d, J = 6.8 Hz, 1H); 13 C NMR (100
MHz, CDCl3 , δ ppm): 77.3, 109.9, 110.9, 112.6, 117.4, 119.4, 125.1,
125.6, 125.7, 125.8, 126.6, 127.8, 127.8, 128.6, 128.6, 128.9, 129.2,
131.5, 137.7, 141.9, 145.7, 147.4. Calcd%: C, 60.37; H, 3.22; N, 6.40;
Found% C, 60.35; H, 3.20; N, 6.38.
4.3. Antibacterial assay
2H-chromene based imidazo[1,2-a]pyridines derivatives were
studied in vitro for antibacterial assay against Gram -ve (E. coli and
K. oxytoca) and Gram +ve (S. aureus and S. pyogene) bacteria for
the zone sizes of inhibitions and MIC assays. Preliminarily, these
cited bacterial strains were procured from CRL, Institute of Medi-
cal Science, and SUM Hospital. Then, bacterial strains were inocu-
lated followed by incubated for 24–48 h. By the by, sterile media
was allowed to aliquot each Petri plates further solidifying, con-
comitantly each well was loaded with test samples at 60μl. There-
after plates were incubated for 24h at 37 ˚C to the estimation of
the zone of inhibition. Moreover, MIC assay was assessed previ-
ously reported [53], 96-well plate with various concentrations at
20 0,10 0,75,50,40,36,32,28,24,20,16,12,8,4 and 2μg/ml. These plates
were allowed to aliquot nutrient broth, bacterial suspension, and
various concentrated test samples. Consequently, individual wells
were treated with TTC dye for monitoring bacterial growth inhibi-
tion [54].
4.4. Molecular docking study
Firstly, 2H-chromene based imidazo [1,2-α ]pyridines derivatives
13(a–q) were drawn virtually by using ChemDraw-v12.0 and each
structure was correctly 2D-geometric optimization with clean-up
errors. Then, each structure was 3D optimized and energy min-
imization by ChemSketch-v2015 and open Babel-v2.4. Concomi-
tantly, the crystal structure of bacterial protein-peptide deformy-
lase (PDBID 1DEF and 1LMH) was retrieved from the protein data
N.P. Mishra, S. Mohapatra, C.R. Sahoo et al.
bank, then removal of heteroatoms and missing side-chains. More-
over, a molecular docking study was performed using Autodock-
v4.2 of this prepared ligand (derivatives) and proteins by integu-
ment of Lamarckian algorithm with each run for 270 0 0 genera-
tions. All the confirmed docking runs were analyzed and the gen-
erated complex was analyzed by BIOVIA DS-v4.5 for intermolecular
residue interactions [55].
Declaration of Competing Interest
The authors declare the following financial interests/personal
relationships which may be considered as potential competing in-
terests:
CRediT authorship contribution statement
Nilima Priyadarsini Mishra: Conceptualization, Methodology,
Writing – original draft. Seetaram Mohapatra: Conceptualiza-
tion, Supervision, Project administration. Chita Ranjan Sahoo: Re-
sources, Software. Bishnu Prasad Raiguru: Data curation. Sabita
Nayak: Writing – review & editing. Subhrakant Jena: Formal anal-
ysis. Rabindra Nath Padhy: Conceptualization.
Acknowledgments
The author NPM acknowledges INSPIRE program
(DST/INSPIRE/03/2015/004518, New Delhi) for providing finan-
cial supports in the form of INSPIRE FELLOWSHIP. The author SRM
is grateful to the CSIR, New Delhi, for the financial support No-
02(0381)/19/EMR-II, for the work.
Supplementary materials
Supplementary material associated with this article can be
found, in the online version, at doi:10.1016/j.molstruc.2021.131183.
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