Design, synthesis, in silico studies, and evaluation of novel chalcones and their pyrazoline derivatives for antibacterial and antitubercular activities

Article abstract of DOI:10.1007/s00044-020-02602-8

A new series of naphthyl chalcones (3a–3p) and their pyrazoline derivatives (4a–4h) were synthesized using substituted acetophenones, substituted naphthaldehydes, and hydrazine hydrate as starting materials. All the synthesized compounds were characterize

Full text of DOI:10.1007/s00044-020-02602-8

MEDICINAL
CHEMISTRY
RESEARCH
Medicinal Chemistry Research
https://doi.org/10.1007/s00044-020-02602-8
ORIGINAL RESEARCH
Design, synthesis, in silico studies, and evaluation of novel
chalcones and their pyrazoline derivatives for antibacterial and
antitubercular activities
1
Shivani Pola1 Karan Kumar Banoth2 Murugesan Sankaranarayanan2 Ramesh Ummani3 Achaiah Garlapati
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Received: 8 January 2020 / Accepted: 6 July 2020
© Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract
A new series of naphthyl chalcones (3a–3p) and their pyrazoline derivatives (4a–4h) were synthesized using substituted
acetophenones, substituted naphthaldehydes, and hydrazine hydrate as starting materials. All the synthesized compounds
were characterized by IR, NMR, and mass spectrometric analysis and screened for antimycobacterial activity against
Mycobacterium tuberculosis H37Rv (ATCC 27924) and antibacterial activity against Staphylococcus aureus (MTCC 96),
Bacillus subtilis (MTCC 441), Escherichia coli (MTCC 443) and Klebsiella pneumonia (MTCC 109). Compounds 3b and 3p
exhibited significant antibacterial activity against all the tested bacterial strains. Amongst the synthesized compounds,
compound 4b with 2-hydroxy-5-bromophenyl substitution at 3rd position of pyrazoline showed significant antimycobacter-
ial activity with MIC of 6.25 µM comparable to that of standard isoniazid. The synthesized compounds were further screened
for their cytotoxic activity against the MDA-MB-231 and SKOV3 cell lines. The compounds 3a, 3l, 4b, 4c, 4e, and 4h did
not exhibit any cytotoxicity, and other compounds exhibited IC50 values higher than 8 and 22 µM against MDA-MB-231 and
SKOV3 cell lines, respectively, compared to 1.20 and 1.30 µM shown by standard doxorubicin. To find out the putative
binding mode of significantly active and weakly active compounds, a molecular docking study was also performed. In that,
the most active compound 4b, displayed a hydrogen bond interaction with docking score of −10.50 kcal/mol and energy of
−44.50 weakly active compound 3h did not show any crucial hydrogen bond interaction with the surrounded amino-acid
residues and revealed a docking score of −6.74 and docking energy of −42.50.
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Keywords Chalcones Pyrazolines Mycobacterium Turbidimetry Cytotoxicity Molecular docking.
Introduction
Tuberculosis (TB) is one of the leading causes of global death,
among other infectious diseases. Over the last four decades,
there is no much change in the TB treatment regimen. The
emergence of drug resistance became thought provoking and
demanding the development of regimens (Farah et al. 2015). In
recent times, novel drugs like bedaquiline, delamanid, and a
few repurposed drugs like clofazimine, linezolid, and carba-
penems are being used in TB patients infected with drug-
resistant mycobacterium. Effective treatment for TB mostly
consists of bactericidal and sterilizing drugs and their combi-
nations for a sufficient duration of action, but in many cases,
the current treatment has been failed to show promising anti-
mycobacterial efficacy and permanent cure. However, existing
drugs and newly approved leads gradually becoming unsa-
tisfactory due to low efficacy, high toxicity, drug resistance,
and prolonged duration of therapy (Sharma et al. 2009).
Supplementary information The online version of this article (https://
doi.org/10.1007/s00044-020-02602-8) contains supplementary
material, which is available to authorized users.
* Achaiah Garlapati
achaiah_g@yahoo.co.in
1
University College of Pharmaceutical Sciences,
Kakatiya University, Warangal, Telangana 506009, India
2
Department of Pharmacy, Medicinal Chemistry Research
Laboratory, Birla Institute of Technology and Science,
Pilani Campus, Pilani, Rajasthan 333031, India
3
Centre for Chemical Biology, Indian Institute of Chemical
Technology, IICT, Tarnaka, Hyderabad, Telangana, India

Medicinal Chemistry Research
Chalcones are chemically 1,3-diaryl-2-propen-1-ones, a
group of natural or synthetic compounds consisting of open-
chain flavonoids, comprises two aromatic rings joined by a
three-carbon α, β-unsaturated carbonyl system, precursors for
the synthesis of various flavonoids and isoflavonoids (Lin et al.
2002). Chalcone has become a vital lead molecule for its
valuable pharmacological activities, including antioxidant
(Ahmad et al. 2013), antibacterial (Kumar et al. 2014), anti-
trypanosomal (Patole et al. 2006), antileishmanial (Lopes et al.
2015), anticancer (Casey et al. 2019), antidiabetic (Zhou et al.
2010), and anti-inflammatory (Kumar et al. 2016) activities.
Licochalcone, a naturally occurring flavonoid with chalcone
moiety, exhibited potent antimycobacterial activity against
several strains of mycobacterium and proved that halogenated
chalcones as potent antitubercular agents (Lin et al. 2002).
Sivakumar et al. (2007) developed a series of chalcone deri-
vatives and drawn their structure–activity relationship with
respect to antitubercular activity. In recent findings, chalcone
derivatives showed promising antimycobacterial activity by
selectively inhibiting various targets like Dihydrofolate reduc-
tase (Hans et al. 2010), Tyrosine phosphatase A (Chiaradia
et al. 2012), Enoyl-Acp reductase (He et al. 2006), etc. Gomes
et al. reported a furanyl containing chalcone ((2E)-3-(5-nitro-
furan-2-yl)-1-[4-(piperidin-1-yl)-phenyl]prop-2-en-1-one) as a
promising antitubercular agent with MIC of 0.07 and 0.03 µM
against Rifampicin (rmp resistant) and isoniazid (inh resistant)
strains (Gomes et al. 2017). Fluorine substituted chalcone, (E)-
3-(4-fluorophenyl)-1-(2,4,6-trimethoxyphenyl)prop-2-ene-1-
one was reported as a potent antitubercular agent by Bur-
maoglu et al. (2017). A series of chalcones were synthesized by
the reaction of 2,5-dimethylthiophene with various heterocyclic
aldehydes and evaluated for antibacterial activity (Khan and
Asiri 2017). Among the series, pyrazole containing chalcone
showed better antibacterial activity (MIC of 16 µg/ml) against
S. typhimurium and Escherichia coli than the reference
chloramphenicol.
pyrazoline derivatives has been proved as an attractive scaf-
folds in developing promising leads with potent biological
activities like antidepressant (Marrapu et al. 2011), antic-
onvulsant (Zhou et al. 2010), antibacterial (Lopes et al. 2015),
antifungal (Figueroa-valverde et al. 2017), antiamoebic
(Nayyar et al. 2006), anti-HIV (Sivakumar et al. 2007), and
anticancer (Sharma et al. 2009). Ahmed and Husain (2016)
synthesized a new set of pyrazoline derivatives and found
significant antimycobacterial and antifungal activity.
At present, the scenario of research and focus of Health
organizations and funding agencies is toward the finding of
novel molecules for safe and effective TB treatment with a
shorter duration, and also to encourage researchers toward
discovery and development of new antitubercular drugs (Cas-
taño et al. 2019). Because of the above, a new series of
naphthyl chalcones and the corresponding pyrazoline deriva-
tives were synthesized by standard protocols, characterized and
screened for antibacterial and antitubercular activity. Designing
of the target compound is shown in Fig. 1.
Experimental
Materials and methods
All the chemicals and solvents were procured from Sigma-
Aldrich Pvt. Ltd. The reactions were monitored with the help of
thin-layer chromatography using pre-coated aluminum sheets,
and column chromatography was performed on silica gel
60–100, 250–400 mesh (Merk) for purification of the com-
pounds. The solvent system of ethyl acetate: hexane and
chloroform: methanol of different ratios was used. The spot
were visualized under a UV lamp. Melting points of the syn-
thesized compounds were determined using MEL TEMP
electro thermal apparatus. IR spectra were acquired on the
1
Perkin Elmer FT-IR spectrometer. Both H NMR and 13C
Naphthalenes have been recognized as a new range of
potent antimicrobials effective against an extensive range of
human pathogens. They occupy a central place among med-
icinally essential compounds due to their diverse and exciting
antibiotic properties with minimum toxicity as well as anti-
mycobacterial properties (Rokade et al. 2010). Interestingly, a
set of naphthyl chalcone-based hybrid molecules were devel-
oped and screened by Chiaradia et al. (2012) for their anti-
NMR spectra of the synthesized compounds were performed
with Bruker Avance-II 400 NMR Spectrometer operating at
400 and 100 MHz, respectively, at Andhra University, Visha-
khapatnam; the chemical shifts were reported in ppm units with
respect to TMS as the internal standard. Mass spectra of the
synthesized compounds were recorded with 6545 QTOF MS/
MS at IICT, Hyderabad. Schrodinger software was used for
molecular docking studies at BITS Pilani, Pilani Campus.
tubercular activity.
A
well-organized structure–activity
relationship was derived for inhibition of Mycobacterium tyr-
osine phosphatase A.
Procedure for synthesis of naphthyl chalcones (3a–3p)
In drug discovery and research, heterocyclic compounds
occupy a central role, and nitrogen-containing moieties
demonstrated a diverse range of pharmacological activities.
Pyrazolines, nitrogen-containing heterocyclic compounds have
been investigated extensively for the generation of novel anti-
microbial agents. Various research findings revealed that
Chalcones were prepared by base-catalyzed condensation of a
mixture of the substituted acetophenones and substituted
naphthaldehydes in ethanol. To the ethanolic solution of sub-
stituted acetophenone (2) (0.1 mol), an equimolar quantity of
substituted naphthaldehyde (1) (0.1 mmol) was added. To the
reaction mixture, aqueous potassium hydroxide (5 ml, 60%)

Medicinal Chemistry Research
was added gradually drop wise with constant stirring, and the
reaction was continued at room temperature under stirring for
14–16 h. The progress of the reaction was supervised using
TLC. The volume of KOH varied according to the reaction
(Lopes et al. 2015). To the reaction mixture, distilled water and
10% hydrochloric acid were added for precipitation of the
compounds (3a–p). Resulting solids were filtered and recrys-
tallized from ethanol.
1-(2-hydroxyphenyl)-3-(naphthalen-1-yl) prop-2-en-1-one
(3c) Compound 3c obtained as light yellow solid (yield
1
63), mp 56–58 °C. H NMR (CDCl3, 400 MHz, δ, TMS =
0): 12.89 (s, 1H, –OH), 8.83–8.79 (d, 1H, H-α, J =
15.2 Hz), 8.32–8.29 (d, 1H, Ar–H J = 8.4 Hz), 8.04–7.92
(m, 1H, Ar–H), 7.80–7.76 (d, 1H, H-β, J = 15.2 Hz),
7.66–7.49 (m, 4H, Ar–H), 7.09–7.07 (d, 1H, Ar–H, J =
8.4 Hz), 7.00–6.97 (t, 1H, Ar–H, J = 7.6 Hz). 13C NMR
(CDCl3, 100 MHz, δ, TMS = 0): 191.8, 162.9, 135.9,
135.8, 133.8, 133.6, 132.0, 129.8 128.8, 128.3, 126.9,
126.3, 126.0, 124.0, 122.9, 121.8, 121.5, 121.2, 118.0.
Anal. Calcd. MS: 274.02; found m/z: 275 (M+ + 1). IR
(KBr, cm−1): 3442.2 (OH), 3032 (C–H, aromatic),
1634.47 (C=O).
Procedure for synthesis of pyrazolines (4a–4h)
To the solution of appropriate chalcone (3a–3p, 0.01 mol) in
ethanol (10 ml), hydrazine hydrate (0.02 mol) was added. To
the reaction mixture, the catalytic amount of glacial acetic acid
was added and refluxed for 8–10 h. The progress of the reac-
tion was monitored using TLC (Ahmad and Husain 2016).
After the end of the reaction, the crude mixture was poured into
ice-cold water, and separated precipitate was filtered off.
Obtained solid compounds (4a–4h) were purified by column
chromatography/recrystallization.
Plausible mechanism involved in the reactions is shown
in Figs. 2 and 3.
Characterization of synthesized compounds is
given below:
1-(4-methoxyphenyl)-3-(naphthalen-1-yl) prop-2-en-1-one
(3d) Compound 3d obtained as yellow solid (yield 73%),
1
mp 52–54 °C. H NMR (CDCl3, 400 MHz, δ, TMS = 0):
8.65–8.61 (d, 1H, H-α, J = 13.6 Hz), 8.60–8.57 (d, 1H,
Ar–H, J = 9.6 Hz), 8.53–8.46 (m, 2H, Ar–H), 8.08–8.05 (d,
1H, H-β, J = 13.2 Hz), 7.98–7.97 (t, 2H, Ar–H, J = 6.8 Hz),
7.65–7.63 (m, 4H, Ar–H), 3.83 (s, 3H, –OCH3). 13C NMR
(CDCl3, 100 MHz, δ, TMS = 0): 189.5, 136.9, 135.8,
133.6, 133.6, 132.2, 132.0, 132.0, 128.9, 128.8, 128.3,
126.9, 126.3, 126.0, 124.6, 122.9, 122.3. Anal. Calcd. MS:
288.12; found m/z: 289.000 (M+ + 1). IR (KBr, cm−1):
3020.28 (C–H, aromatic), 1649.28 (C=O).
1-(5-bromo-2-hydroxyphenyl)-3-(naphthalen-1-yl)prop-2-
en-1-one (3a) Compound 3a obtained as orange solid
1
(yield 70%), mp 58–60 °C. H NMR (CDCl3, 400 MHz, δ,
TMS = 0): 12.81 (s, 1H, –OH), 8.86–8.82 (d, 1H, H-α, J =
14.8 Hz), 8.30–8.28 (d, 1H, Ar–H, J = 8.4 Hz), 8.08–8.07
(d, 1H, Ar–H, J = 2.4 Hz), 7.95–7.93 (d, 1H, Ar–H, J =
8.0 Hz), 7.70–7.56 (m, 5H, Ar–H & H-β), 7.00–6.98 (d, 1H,
J = 8.8 Hz). 13C NMR (CDCl3, 100 MHz, δ, TMS = 0):
192.8, 162.8, 138.6, 135.8, 134.9, 133.6, 133.5, 132.6,
128.8, 128.3, 126.9, 126.5, 126.0, 124.3, 122.9, 122.6,
121.3, 119.7, 116.5. Anal. Calcd. MS: 353.211; found m/z:
353.000 (M+), 355.000 (M+ + 2). IR (KBr, cm−1): 3468.29
(–OH), 2956.23 (C–H, aliphatic), 1656.27 (C=O).
1-(5-bromo-2-hydroxyphenyl)-3-(2-methoxynaphthalen-1-
yl)prop-2-en-1-one (3e) Compound 3e obtained as yel-
1
lowish orange solid (yield 74%), mp 60–62 °C. H NMR
(CDCl3, 400 MHz, δ, TMS = 0): 12.97 (s, 1H, –OH), 10.92
(s, 1H, Ar–H), 9.31–9.29 (d, 1H, Ar–H, J = 7.2 Hz),
8.68–8.65 (d, 1H, H-α, J = 14.8 Hz), 8.28–7.28 (m, 6H,
Ar–H), 8.07–8.03 (d, 1H, H-β, J = 14.0 Hz), 6.98–6.97 (d,
1H, Ar–H, J = 7.6 Hz). 4.08 (s, 1H, –OCH3). 13C NMR
(CDCl3, 100 MHz, δ, TMS = 0): 192.5, 162.4, 151.2,
145.6, 138.6, 134.5, 130.6, 129.8, 129.7, 128.5, 126.7,
124.2, 122.8, 121.3, 119.7, 119.2, 116.2, 114.8, 56.4. Anal.
Calcd. MS: 383.02; found m/z: 383 (M+), 385 (M+ + 2). IR
(KBr, cm−1): 3456.28 (OH), 2978.23 (C–H, aliphatic),
1649.58 (C=O).
1-(2, 4-dichlorophenyl)-3-(naphthalen-1-yl)prop-2-en-1-one
(3b) Compound 3b obtained as cream solid (yield 68%),
1
mp 62–64 °C. H NMR (CDCl3, 400 MHz, δ, TMS = 0):
8.42–8.38 (d, 1H, H-α, J = 15.6 Hz), 8.14–8.12 (d, 1H,
Ar–H, J = 8.4 Hz), 7.97–7.95 (d, 1H, Ar–H, J = 8 Hz),
7.92–7.87 (m, 2H, Ar–H), 7.63–7.58 (m, 5H, Ar–H & H-β),
7.43–740 (dd, 1H-Ar, J = 2.0 Hz), 7.285–7.28 (d, 1H,
Ar–H, J = 1.6 Hz), 7.24 (s, 1H, Ar–H). 13C NMR (CDCl3,
100 MHz, δ, TMS = 0): 189.6, 146.5, 135.9, 135.1, 133.6,
133.2, 132.7, 132.0, 131.8, 129.5, 128.8, 128.3, 127.5,
126.9, 126.3, 126.1, 124.0, 122.3, 121.5. Anal. Calcd. MS:
327.029; found m/z: 327.000 (M+), 329.000 (M+ + 2). IR
(KBr, cm−1): 3056.95 (C–H, aromatic), 2986.36 (C–H,
aliphatic), 1648.32 (C=O).
1-(2-hydroxyphenyl)-3-(2-methoxynaphthalen-1-yl)prop-2-
en-1-one (3f) Compound 3f obtained as white solid (yield
1
75%), mp 62–64 °C. H NMR (CDCl3, 400 MHz, δ, TMS
= 0): 10.92 (s, 1H, –OH), 8.67–8.64 (d, 1H, H-α, J =
15.6 Hz), 8.31–8.29 (d, 1H, Ar–H, J = 8.8 Hz), 8.11–8.07
(m, 6H, Ar–H & H-β), 7.93–7.32 (m, 6H, Ar–H), 7.26–7.08
(d, 1H, Ar–H, J = 8.4 Hz), 6.98–6.95 (t, 1H, Ar–H, J =
7.6 Hz), 4.11 (s, 3H, –OCH3). 13C NMR (CDCl3, 100 MHz,
δ, TMS = 0): 192.9, 163.2, 150.0, 145.2, 139.6, 138.4,
130.0, 129.8, 129.2, 128.6, 126.7, 124.8, 123.4, 122.7,

Medicinal Chemistry Research
Fig. 1 Designing approach of
the target compounds
121.6, 121.4, 119.8, 116.2, 114.8, 56.3. Anal. Calcd. MS:
304.339; found m/z: 305.000 (M+ + 1). IR (KBr, cm−1):
3428.96 (OH), 3002.32 (C–H, aromatic), 2856.45 (C–H,
aliphatic), 1652.39 (C=O).
130.4, 129.7, 129.1, 128.6, 126.7, 124.6, 123.8, 122.6,
121.4, 119.35, 116.2, 114.5, 56.3. Anal. Calcd. MS: 367.24;
found m/z: 367.000 (M+), 369.00 (M+ + 2). IR (KBr,
cm−1): 3028.92 (C–H, aromatic), 1649.63 (C=O).
1-(4-bromophenyl)-3-(2-methoxynaphthalen-1-yl)prop-2-
3-(2-methoxynaphthalen-1-yl)-1-(4-methoxyphenyl)prop-2-
en-1-one (3g) Compound 3g obtained as white solid (yield
75%), mp 52–54 °C. H NMR (CDCl3, 400 MHz, δ, TMS
en-1-one (3h) Compound 3h obtained as cream solid
(yield 65%), mp 56–58 °C. H NMR (CDCl3, 400 MHz, δ,
1
1
= 0): 10.95 (s, 1H, –OH), 8.65–8.62 (d, 1H, H-α, J =
15.6 Hz), 8.18–8.09 (d, 1H, Ar–H, J = 8.8 Hz), 7.90–7.72
(m, 6H, Ar–H), 7.37–7.22 (m, 4H, Ar–H & H-β), 7.16–7.05
(d, 1H, Ar–H, J = 8.4 Hz), 6.98–6.95 (t, 1H, Ar–H, J =
7.6 Hz), 3.96 (s, 3H, –OCH3). 13C NMR (CDCl3, 100 MHz,
δ, IMS = 0): 192.6, 163.4, 150.5, 145.2, 139.7, 138.5,
TMS = 0): 8.51–8.47 (d, 1H, H-α, J = 16.0 Hz), 8.30–8.28
(d, 1H, Ar–H J = 8.4 Hz), 8.11–8.09 (d, 2H, Ar–H, J =
8.8 Hz), 7.92–7.88 (m, 2H, Ar–H & H-β), 7.84–7.82 (d, 1H,
Ar–H, J = 8.0 Hz), 7.56–754 (t, 1H, Ar–H, J = 8.0 Hz),
7.44–7.40 (t, 1H, Ar–H, J = 7.6 Hz), 7.36–7.34 (d, 1H,
Ar–H, J = 9.2 Hz), 7.03–7.01 (d, 2H, Ar–H, J = 8.8 Hz),

Medicinal Chemistry Research
Fig. 2 Plausible mechanism for
the napthylchalcones (3a–p)
4.07 (s, 3H, –OCH3), 3.92 (s, 3H,–OCH3). 13C NMR
(CDCl3, 100 MHz, δ, TMS = 0): 190.8, 163.5, 158.5,
143.3, 132.9, 131.8, 131.8, 129.5, 127.9, 127.3, 126.9,
123.8, 122.9, 122.8, 122.7, 118.8, 110.3, 55.9, 55.8. Anal.
Calcd. MS: 318.37; found m/z: 319.000 (M+ + 1). IR (KBr,
cm−1): 3067.45 (C–H, aromatic), 2964.52 (C–H, aliphatic)
1652.23 (–C=O).
NMR (CDCl3, 100 MHz, δ, TMS = 0): 192.8, 162.8, 153.2,
138.8, 135.8, 134.9, 131.2, 126.5, 125.5, 125.3, 124.5,
124.0, 123.3, 123.1, 121.0, 119.7, 116.2, 103.0, 56.2. Anal.
Calcd. MS: 383.24; found m/z: 383 (M+), 385 (M+ + 2). IR
(KBr, cm−1): 3442.42 (OH), 3067.45 (C–H, aromatic),
2956.54 (C–H, aliphatic), 1646.16 (C=O).
1-(4-bromophenyl)-3-(4-methoxynaphthalen-1-yl) prop-2-
1-(5-bromo-2-hydroxyphenyl)-3-(4-methoxynaphthalen-1-
yl) prop-2-en-1-one (3i) Compound 3i obtained as orange
solid (yield 74%), mp 62–64 °C. 1H NMR (CDCl3,
400 MHz, δ, TMS = 0): 12.97 (s, 1H, O–OH), 10.23 (s, 1H,
Ar–H), 9.34–9.31 (d, 1H, Ar–H, J = 8.8 Hz), 8.83–8.79 (d,
1H, H-α, J = 15.2 Hz), 8.32–8.31 (m, 1H), 8.29–8.27 (d,
1H, Ar–H, J = 8.4 Hz), 8.07 (s, 1H, Ar–H), 8.02–8.00 (d,
1H-Ar, J = 8.0 Hz), 7.96–7.94 (d, 1H, Ar–H, J = 8.0 Hz),
en-1-one (3j) Compound 3j obtained as light cream solid
(yield 75%), mp 62–64 °C. H NMR (CDCl3, 400 MHz, δ,
1
TMS = 0): 8.68–8.64 (d, 1H, H-α, J = 15.2 Hz), 8.36–8.31
(m, 1H, Ar–H), 8.26–8.24 (d, 1H, Ar–H, J = 8.4 Hz),
8.08–8.06 (d, 1H, Ar–H, J = 8.8 Hz), 7.96–7.92 (t, 2H,
Ar–H, J = 8.0 Hz), 7.81–7.79 (d, 1H, Ar–H, J = 8.4 Hz),
7.69–7.62 (m, 3H, Ar–H & H-β), 3.98 (s, 3H, –OCH3). 13
C
NMR (CDCl3, 100 MHz, δ, TMS = 0): 189.7, 153.2, 136.9,
135.8, 132.2, 131.8, 130.2, 128.0, 126.5, 125.4, 125.2,
7.74–7.56 (m, 3H, Ar–H & H-β), 4.13 (s, 3H, –OCH3). 13
C

Medicinal Chemistry Research
Fig. 3 Plausible mechanism for
the napthylpyrazoline (4a–h)
124.0, 123.6, 123.6, 121.0, 116.8, 103.9, 56.3.Anal. Calcd.
MS: 367; found m/z: 367.000 (M+), 369.000 (M+ + 2). IR
(KBr, cm−1): 3002.86 (C–H, aromatic), 2989.56 (C–H,
aliphatic), 1652.23 (C=O).
Ar–H, J = 9.6 Hz), 7.23–7.21 (d, 1H, Ar–H, J = 8.8 Hz),
3.83 (s, 3H, –OCH3), 3.78 (s, 3H, –OCH3). 13C NMR
(CDCl3, 100 MHz, δ, TMS = 0): 189.5, 166.6, 153.2,
135.8, 130.0, 130.2, 126.6, 125.3, 125.3, 125.1, 124.2,
123.6, 121.5, 121.0, 116.5, 114.8, 103.2, 56.2, 55.6. Anal.
Calcd. MS: 318.37; found m/z: 319.000 (M+ + 1). IR (KBr,
cm−1): 3002.56 (C–H, aromatic), 2906.56 (C–H, aliphatic),
1643.89 (C=O).
3-(4-methoxynaphthalen-1-yl)-1-(4-methoxyphenyl) prop-
2-en-1-one (3k) Compound 3k obtained as light yellow
solid (yield 78%), mp 62–64 °C. 1H NMR (CDCl3,
400 MHz, δ, TMS = 0): 8.64–8.62 (d, 2H, Ar–H, J =
5.6 Hz), 8.61–8.58 (d, 2H, Ar–H, J = 9.2 Hz), 8.32–8.28 (d,
1H, H-α, J = 15.2 Hz), 7.98–7.95 (d, 1H, H-β, J = 14.8 Hz),
7.56–7.53 (d, 4H, Ar–H, J = 10.4 Hz), 7.280–7.256 (d, 1H,
1-(2-hydroxyphenyl)-3-(4-methoxy naphthalene-1-yl) prop-
2-en-1-one (3l) Compound 3l obtained as yellow solid
1
(yield 74%), mp 60–62 °C. H NMR (CDCl3, 400 MHz, δ,

Medicinal Chemistry Research
TMS = 0): 11.02 (s, 1H, –OH), 8.67–8.64 (d, 1H, H-α, J =
15.6 Hz), 8.31–8.29 (d, 1H, Ar–H, J = 8.8 Hz), 8.11–8.07
(m, 6H, Ar–H & H-β), 7.93–7.32 (m, 6H, Ar–H), 7.26–7.08
(d, 1H, Ar–H, J = 8.4 Hz), 6.98–6.95 (t, 1H, Ar–H, J =
7.6 Hz), 3.82 (s, 3H, –OCH3). 13C NMR (CDCl3, 100 MHz,
δ, TMS = 0): 192.6, 163.5, 153.2, 135.5, 132.9, 131.8,
129.8, 126.9, 125.7, 125.6, 125.1, 124.5, 123.2, 121.8,
121.6, 121.1, 118.3, 116.5, 103.8, 56.2. Anal. Calcd. MS:
304.339; found m/z: 305.000 (M+ + 1). IR (KBr, cm−1):
3020.56 (C–H, aromatic), 1652.56 (C=O).
3-(6-methoxynaphthalen-2-yl)-1-(4-nitrophenyl)prop-2-en-
1-one (3p) Compound 3p obtained as light brown solid
1
(yield 74%), mp 60–62 °C. H NMR (CDCl3, 400 MHz, δ,
TMS = 0): 8.89 (s, 1H, Ar–H), 8.48–8.46 (d, 1H, Ar–H,
J = 8.4 Hz), 8.41–8.39 (d, 1H, Ar–H, J = 7.6 Hz), 8.08
(s, 1H, Ar–H), 8.05–8.03 (d, 1H, Ar–H, J = 5.2 Hz),
7.84–7.33 (m, 4H, Ar–H), 7.64–7.60 (d, 1H, H-α, J =
15.6 Hz), 7.24–7.19 (m, 2H, Ar–H & H-β), 3.98 (s, 3H,
–OCH3). 13C NMR (CDCl3, 100 MHz, δ, TMS = 0):
189.79, 157.65, 153.28, 145.25, 144.32, 138.90, 131.23,
130.95, 129.83, 127.56, 127.08, 126.56, 124.85, 124.42,
121.35, 119.65, 105.85, 55.68. Anal. Calcd. MS: 333.34;
found m/z: 334.23 (M+ + 1). IR (KBr, cm−1): 3016.62
1-(5-bromo-2-hydroxyphenyl)-3-(6-methoxynaphthalen-2-
yl)prop-2-en-1-one (3m) Compound 3m obtained as
1
orange solid (yield 75%), mp 64–66 °C. H NMR (CDCl3,
(C–H,
aromatic),
2978.32
(C–H,
aliphatic),
400 MHz, δ, TMS = 0): 11.02 (s, 1H, –OH), 8.65–8.32 (d,
1H, H-α, J = 14.6 Hz), 8.21–8.09 (d, 1H, Ar–H, J =
8.6 Hz), 8.01–7.78 (m, 6H, Ar–H), 7.65–7.32 (m, 6H, Ar–H
& H-β), 7.26–7.08 (d, 1H, Ar–H, J = 8.4 Hz), 6.88–6.75 (t,
1H, Ar–H, J = 7.6 Hz), 3.78 (s, 3H, –OCH3). 13C NMR
(CDCl3, 100 MHz, δ, TMS = 0): 189.7, 166.5, 157.3,
145.2, 135.9, 131.2, 130.9, 130.2, 129.6, 129.3, 127.5,
127.2, 126.6, 121.5, 119.5, 114.8, 114.2, 105.7, 55.8. Anal.
Calcd. MS: 383.24; found m/z: 383 (M+), 385 (M+ + 2). IR
(KBr, cm−1): 3452.88 (OH), 3089.28 (C–H, aromatic),
2923.63 (C–H, aliphatic), 1662.5 (C=O).
1642.38 (C=O).
3-(4-methoxyphenyl)-5-(naphthalen-1-yl)-4,5-dihydro-1H-
pyrazole (4a) Compound 4a obtained as light brown solid
(yield 65%), mp 114–116 °C. H NMR (CDCl3, 400 MHz, δ,
1
TMS = 0): 8.36–8.34 (d, 2H, Ar–H, J = 8.8 Hz), 8.02–7.99 (d,
2H, Ar–H, J = 11.6 Hz), 7.85–7.11 (t, 1H, Ar–H, J = 8.8 Hz),
7.44–7.41 (m, 3H, Ar–H), 7.26–7.24 (d, 2H, Ar–H, J =
8.4 Hz), 6.95 (1H, –NH-pyrazoline), 4.26–4.21 [1H, H-x
(pyrazoline), J = 8.8 Hz], 3.92 (s, 3H, –OCH3), 3.52–3.47 (dd,
1H, Hb, J = 8.8, 15.2 Hz), 3.215–3.168 (dd, 1H, Ha, J = 9.6,
15.2 Hz). 13C NMR (CDCl3, 100 MHz, δ, TMS = 0): 163.2,
151.2, 137.8, 130.9, 130.5, 128.9, 128.7, 128.5, 126.4, 125.8,
125.6, 122.9, 122.6, 114.6, 55.6, 48.9, 43.2. Anal. Calcd. MS:
302.37; found m/z: 303 (M+ + 1). IR (KBr, cm−1): 3258.56
(NH), 2924.54 (C–H, aliphatic), 1589.34 (C=N), 1398.56
(C–N).
3-(6-methoxynaphthalen-2-yl)-1-(4-methoxyphenyl)prop-2-
en-1-one (3n) Compound 3n obtained as pale yellow
solid (yield 78%), mp 66–68 °C. 1H NMR (CDCl3,
400 MHz, δ, TMS = 0): 7.90 (s, 1H, Ar–H), 7.79–7.73
(m, 4H, Ar–H & H-α), 7.69–7.65 (m, 3H, Ar–H & H-β),
7.214–7.16 (m, 3H, Ar–H), 6.83–6.39 (d, 1H, Ar–H, J =
6.4 Hz), 3.96 (s, 3H, –OCH3), 3.43 (s, 3H, –OCH3). 13C
NMR (CDCl3, 100 MHz, δ, TMS = 0): 189.9, 166.8,
157.2, 145.2, 138.2, 131.2, 130.9, 130.2, 129.5, 127.6,
126.3, 121.5, 119.5, 114.2, 105.6, 55.8, 55.2. Anal.
Calcd. MS: 318.37; found m/z: 319.000 (M+ + 1). IR
(KBr, cm−1): 3025.32 (C–H, aromatic), 2856.95 (C–H,
aliphatic), 1648.32 (C=O).
4-bromo-2-[5-(naphthalen-1-yl)-4,5-dihydro-1H-pyrazol-3-
yl]phenol (4b) Compound 4b obtained as light cream solid
(yield 68%), mp 124–126 °C. H NMR (CDCl3, 400 MHz,
1
δ, TMS = 0):12.81 (s, 1H, –OH), 10.48 (s, 1H, Ar–H),
8.11–7.75 (m, 5H, Ar–H), 7.46–7.39 (m, 4H, Ar–H &
pyrazoline-NH), 3.81–3.74 [dd, 1H, H-x (pyrazoline), J =
8.4 Hz], 3.44–3.41 (dd, 1H, Hb, J = 8.4, 14.2 Hz),
3.23–3.17 (dd, 1H, Ha, J = 10.4, 14.2 Hz). 13C NMR
(CDCl3, 100 MHz, δ, TMS = 0): 161.0, 152.7, 137.8,
135.6, 134.2, 130.9, 130.6, 128.8, 128.6, 126.7, 125.6,
125.4, 122.9, 122.6, 121.4, 119.3, 49.6, 43.3. Anal. Calcd.
MS: 367.24; found m/z: 367.00 (M+), 369.00(M+ + 2). IR
(KBr, cm−1): 3736.29 (OH), 3398.24 (NH), 3042.54 (C–H,
aromatic), 1585.58 (C=N), 1392.45 (C–N).
1-(4-bromophenyl)-3-(6-methoxynaphthalen-2-yl)prop-2-
en-1-one (3o) Compound 3o obtained as yellowish
orange solid (yield 75%), mp 54–56 °C. 1H NMR
(CDCl3, 400 MHz, δ, TMS = 0): 8.00–7.93 (m, 4H,
Ar–H), 7.81–7.78 (m, 3H, Ar–H), 7.69–7.67 (d, 2H,
Ar–H, J = 8.4 Hz), 7.58–7.54 (d, 1H, H-α, J = 15.6 Hz),
7.22–7.17 (m, 2H, Ar–H & H-β), 3.97 (s, 3H, –OCH3).
13C NMR (CDCl3, 100 MHz, δ, TMS = 0): 189.65,
158.20, 145.65, 138.28, 136.92, 132.25, 131.02, 130.06,
129.65, 128.52, 127.50, 127.05, 126.52, 121.30, 119.56,
114.85, 55.8. Anal. Calcd. MS: 367.24; found m/z:
367.00 (M+), 369.00(M+ + 2). IR (KBr, cm−1): 3023.56
(C–H, aromatic), 1646.58 (C=O).
3-(4-bromophenyl)-5-(2-methoxynaphthalen-1-yl)-4,5-dihy-
dro-1H-pyrazole (4c) Compound 4c obtained as white
solid (yield 70%), mp 118–120 °C. 1H NMR (CDCl3,
400 MHz, δ, TMS = 0): 8.02–8.01 (d, 1H, Ar–H, J =
7.2 Hz), 7.99–7.97 (d, 1H, Ar–H, J = 8.0 Hz), 7.72–7.70 (d,
2H, Ar–H, J = 7.2 Hz), 7.58–7.56 (d, 2H, Ar–H, J =

Medicinal Chemistry Research
7.2 Hz), 7.54–7.52 (d, 1H, Ar–H, J = 8.0 Hz), 7.46–7.44 (d,
1H, Ar–H, J = 8.8 Hz), 7.04–7.01 (m, 2H, Ar–H), 6.92 (s,
1H, –NH-pyrazoline), 4.25–4.19 [dd, 1H, H-x (pyrazoline),
J = 7.8 Hz], 3.96–3.90 (dd, 1H, Hb, J = 7.8, 11.2 Hz), 3.83
(s, 3H, –OCH3), 3.21–3.16 (dd, 1H, Ha, J = 8.4, 11.2 Hz).
13C NMR (CDCl3, 100 MHz, δ, TMS = 0): 153.2, 151.7,
135.6, 132.6, 131.4, 129.2, 128.6, 128.0, 126.3, 125.4,
124.6, 123.5, 118.4, 111.6, 56.2, 43.5, 43.3. Anal. Calcd.
MS: 381.27; found m/z: 381 (M+), 383 (M+ + 2). IR (KBr,
cm−1): 3442.96 (NH), 3070.63 (C–H, aromatic), 1566.44
(C=N), 1376.98 (C–N).
8.4, 12.8 Hz), 3.16–3.08 (dd, 1H, Ha, J = 10.4, 12.8 Hz).
13C NMR (CDCl3, 100 MHz, δ, TMS = 0): 162.9, 155.2,
151.7, 133.5, 132.3, 129.6, 128.8, 128.7, 126.1, 124.8,
124.7, 124.0, 123.8, 114.5, 104.9, 56.2, 55.8, 49.4, 43.2.
Anal. Calcd. MS: 333.40; found m/z: 334.00 (M+ + 1). IR
(KBr, cm−1): 3249.65 (NH), 2987.29 (C–H, aliphatic),
1569.56 (C=N).
3-(4-bromophenyl)-5-(6-methoxynaphthalen-2-yl)-4,5-dihy-
dro-1H-pyrazole (4g) Compound 4g obtained as pale
yellow solid (yield 74%), mp 142–144 °C. 1H NMR
(CDCl3, 400 MHz, δ, TMS = 0): 7.76–7.71 (t, 4H,
Ar–H, J = 9.2, 9.6 Hz), 7.58–7.40 (m, 5H, Ar–H),
7.18–7.15 (m, Ar–H, –NH-pyrazoline), 5.12–5.07 (q,
1H, H-x J = 10.8, 8.8 Hz), 3.97 (s, 1H, –OCH3),
3.55–3.49 (dd, 1H, Hb, J = 10.8, 16 Hz), 3.15–3.09 (dd,
1H, Ha, J = 8.8, 16 Hz). 13C NMR (CDCl3, 100 MHz, δ,
TMS = 0): 157.7, 151.4, 134.1, 132.0, 131.9, 129.7,
129.3, 128.8, 128.7, 126.0, 124.7, 122.8, 119.1, 105.7,
55.3, 52.3, 41.1. Anal. Calcd. MS: 381.24; found m/z:
381 (M+), 383 (M+ + 2). IR (KBr, cm−1): 3442.96
(NH), 3070.63 (C–H, aromatic), 2924.13 (C–H, ali-
phatic), 1612 (C=N).
4-bromo-2-(5-(2-methoxynaphthalen-1-yl)-4,5-dihydro-1H-
pyrazol-3-yl)phenol (4d) Compound 4d obtained as pale
yellow solid (yield 75%), mp 132–134 °C. 1H NMR
(CDCl3, 400 MHz, δ, TMS = 0): 11.28 (s, 1H, –OH), 8.48
(s, 1H, Ar–H), 8.39–8.37 (d, 1H, Ar–H, J = 8.4 Hz),
8.00–7.98 (d, 1H, Ar–H, J = 8.0 Hz), 7.83–7.78 (t, 1H-Ar,
J = 10.2 Hz), 7.44–7.416 (m, 3H, Ar–H & –NH-pyrazo-
line), 6.993–6.973 (d, 1H-Ar, J = 8.0 Hz), 6.93–6.89 (t, 1H-
Ar, J = 9.2 Hz), 6.80 (s, 1H, –NH), 4.11–4.07 [t, 1H, H-x
(pyrazoline), J = 8.4 Hz], 3.95 (s, 3H, –OCH3), 3.75–3.68
(dd, 1H, Hb, J = 11.2, 8.4 Hz), 3.22–3.16 (dd, 1H, Ha, J =
10.8, 11.2 Hz). 13C NMR (CDCl3, 100 MHz, δ, TMS = 0):
162.5, 153.2, 151.6, 135.3, 134.5, 133.6, 129.5, 128.3,
128.0, 126.3, 124.3, 123.5, 121.0, 119.3, 118.5, 115.8,
111.6, 55.8, 44.2, 43.8. Anal. Calcd. MS: 397.27; found m/
z: 397 (M+), 399 (M+ + 2). IR (KBr, cm−1): 3286.98 (NH),
2989.56 (C–H, aliphatic), 1554.56 (C=N).
4-bromo-2-(5-(6-methoxynaphthalen-2-yl)-4,5-dihydro-1H-
pyrazol-3-yl)phenol (II-4h) Compound 4h obtained as light
brown solid (yield 74%), mp 152–154 °C. 1H NMR
(CDCl3, 400 MHz, δ, TMS = 0): 11.28 (s, 1H, –OH),
7.76–7.71 (m, 2H, Ar–H), 7.58–7.47 (m, 4H, Ar–H),
7.19–7.14 (m, 3H, Ar–H), 6.86 (s, 1H, –NH-pyrazoline),
5.12–5.07 [t, 1H, H-x (pyrazoline), J = 8.4 Hz], 3.98 (s, 1H,
–OCH3), 3.55–3.49 (dd, 1H, Ha, J = 8.4, 12 Hz), 3.15–3.09
(dd, 1H, Hb, J = 9.6, 12 Hz). 13C NMR (CDCl3, 100 MHz,
δ, TMS = 0): 161.56, 156.28, 151.75, 135.62, 134.28,
132.80, 132.68, 129.56, 129.35, 128.56, 126.65, 124.20,
121.05, 119.56, 115.85, 105.25, 55.65, 51.28, 42.95. Anal.
Calcd. MS: 397.27; found m/z: 397 (M+), 399 (M+ + 2). IR
(KBr, cm−1): 3269.56 (NH), 2896.24 (C–H, aromatic),
1572.64 (C=N) (Table 1).
3-(4-bromophenyl)-5-(4-methoxynaphthalen-1-yl)-4,5-dihy-
dro-1H-pyrazole (4e) Compound 4e obtained as white
solid (yield 68%), mp 128–130 °C. 1H NMR (CDCl3,
400 MHz, δ, TMS = 0): 8.11–8.39(m, 10H, Ar–H), 6.19 (s,
1H, –NH-pyrazoline), 5.74–5.69 [t, 1H, H-x (pyrazoline),
J = 10.4 Hz], 4.14 (s, 3H, –OCH3), 3.81–3.74 (dd, 1H, Ha,
J = 10.4, 16 Hz), 3.23–3.17 (dd, 1H, Hb, J = 8.4, 16 Hz).
13C NMR (CDCl3, 100 MHz, δ, TMS = 0): 156.2, 152.1,
135.6, 133.8, 132.3, 131.7, 129.6, 128.5, 126.2, 125.4,
124.8, 124.0, 123.8, 104.9, 56.3, 49.4, 43.2. Anal. Calcd.
MS: 381.27; found m/z: 381 (M+), 383 (M+ + 2). IR (KBr,
cm−1): 3328.29 (NH), 2956.65 (C–H, aliphatic),
1562.68 (C=N).
In vitro antibacterial activity
The MIC for antibacterial activity of synthesized com-
pounds was determined by the serial dilution technique
using Mueller–Hinton nutrient broth, and ciprofloxacin was
used as standard. The stock solution of test compounds
(4 mg/ml) was prepared in dimethylformamide (DMF) and
sterilized by membrane filtration method using 0.22-µm
pore size polycarbonate sterile membrane (Nuclepore) fil-
ters. Various concentrations of test compounds were pre-
pared in the range of 1–1000 μg/ml by serial dilution. The
total four bacterial strains used for screening antibacterial
activity were Staphylococcus aureus (MTCC 96), Bacillus
5-(4-methoxynaphthalen-1-yl)-3-(4-methoxyphenyl)-4,5-
dihydro-1H-pyrazole (4f) Compound 4f obtained as cream
solid (yield 65%), mp 112–114 °C. 1H NMR (CDCl3,
400 MHz, δ, TMS = 0): 8.47–8.00 (m, 3H, Ar–H),
7.87–7.84 (d, 1H, Ar–H, J = 9.6 Hz), 7.98–7.89 (m, 4H,
Ar–H), 7.69–7.67 (d, 1H, Ar–H, J = 7.6 Hz), 7.19–7.17 (d,
1H, Ar–H, J = 8.0 Hz), 6.91 (s, 1H, –NH-pyrazoline),
4.56–4.14 [t, 1H, H-x, pyrazoline, J = 8.4 Hz] 3.96 (s, 3H,
–OCH3), 3.93 (s, 3H, –OCH3), 3.49–3.42 (dd, 1H, Hb, J =

Medicinal Chemistry Research
OD600 values using TECAN Infinite 200 PROTM (Tecan
Instruments, Switzerland). Positive controls were included
in every assay plate using stock solutions of INH (10 mg/
ml, HiMedia) and rmp (10 mg/ml, HiMedia) to achieve the
final concentration of 0.5, 1, 2, 4, 8, and 16 mg/ml for INH
and 0.25, 0.5, 1, 2, 4, and 8 mg/ml for rmp. Additional
controls DMSO (solvent without compound) and medium
without inoculums were included in all the assay plates
avoiding intra assay variability. The results were analyzed
as the percentage of growth inhibition. All experiments
were carried out in triplicates, and results were reported as
minimum inhibitory concentration (MIC) in µM.
Table 1 Derivatives of the synthesized compounds
Compound
–R
–R1
Compound
–R
–R1
3a
3b
3c
3d
3e
3f
H
H
H
H
5-Br, 2-OH 3m
6-OMe 5-Br, 2-OH
6-OMe 4-OMe
6-OMe 4-Br
2,4-diCl
2-OH
3n
3o
3p
4-OMe
6-OMe 4-NO2
2-OMe 5-Br, 2-OH 4a
H
H
4-OMe
2-OMe 2-OH
2-OMe 4-Br
2-OMe 4-OMe
4b
4c
4d
5-Br, 2-OH
3g
3h
3i
2-OMe 4-Br
2-OMe 5-Br, 2-OH
4-OMe 4-Br
4-OMe 5-Br, 2-OH 4e
3j
4-OMe 2-OH
4-OMe 4-Br
4-OMe 4-OMe
4f
4-OMe 4-OMe
6-OMe -4-Br
3k
3l
4g
4h
6-OMe -5-Br, 2-OH
In vitro cytotoxic studies
subtilis (MTCC 441), E. coli (MTCC 443), Klebsiella
pneumonia (MTCC 109). A standard protocol was followed
to evaluate antibacterial activity (Malothu et al. 2015). Test
compounds at various concentrations were added to the
sterile culture medium in a sterilized borosilicate test tube
and bacterial strain inoculated at 106 CFU/ml concentration.
The tubes were incubated at 37 °C for 24 h and then
examined for the presence or absence of visible growth of
the test organisms. The MIC values were determined by
considering the lowest concentration of the test compound,
where the tubes remained clear, indicating that the bacterial
growth was completely inhibited at this concentration.
Simultaneously, controls were maintained by employing
DMF to observe the solvent effects. SAR is presented in
“Results and discussion.”
Cell lines used in this study were purchased from the ATCC.
The synthesized compounds were evaluated for their in vitro
antiproliferative activity in two different human cancer cell
lines by Resazurin assay (Rachakonda et al. 2013). MDA-
MB-231 (breast cancer cell lines) and SKOV3 (ovarian cancer
cell lines) were grown in Dulbecco’s modified Eagle medium
(containing 10% FBS in a humidified atmosphere of 5% CO2
at 37 °C) containing nonessential amino acids. The cell lines
were grown in their respective media and seeded into 96-well
microtiter plates in 100 µl aliquots at plating densities
depending on the doubling time of individual cell lines. The
microtiter plates were incubated at 37 °C, 5% CO2, 95% air,
and 100% relative humidity for 24 h before the addition of
test compounds and standard. Four concentrations of test
compounds (0.1, 1, 10, and 100 µM) were evaluated as per
the NCI cell line screening protocol, and each was done in
triplicate well. The assay was terminated by the addition of
50 µl of Resazurin solution and incubated for 60 min at 37 °C.
The Fluorescence Intensity was read on a multimode plate
reader (TECAN Infinite 200 PRO™) at a wavelength of
560 nm excitation/590 nm emission. The potency
of compounds is expressed in IC50 and presented in
Table 4.
Antimycobacterial screening assay
Antimycobacterial activity of the synthesized compounds
was performed with Mycobacterium tuberculosis strain
(American Type Culture Collection (ATCC) 27924) using
growth inhibition assay by turbidimetry (Rachakonda et al.
2013). Isolated single colonies of M. tuberculosis from
7H10 agar plate were grown overnight in Middlebrook 7H9
medium (0.47% Middlebrook 7H9 broth base, 10% ADS,
0.2% glycerol, and 0.1% Tween-80) to mid-exponential
phase at 37 °C. Subsequently, 5 ml of Middlebrook 7H9
broth were inoculated with the overnight grown culture and
In silico prediction of physicochemical and ADMET
parameters
Physicochemical parameters of the designed compounds were
in silico predicted using the Qik-prop module of Schrödinger.
Various parameters predicted were; molecular weight (M.
Wt.), total solvent-accessible volume, number of hydrogen
bond donor (HBD), number of hydrogen bond acceptor
(HBA), Vander wall polar surface area of nitrogen and oxy-
gen atoms, octanol/water partition coefficient (log P), aqueous
solubility (Log S), predicted apparent Caco-2 cell perme-
ability in nm/s (PCaco), apparent Madin Darby Canine Kid-
ney permeability and percentage of human oral absorption.
The detailed predicted values were presented in Table 5.
͌
allowed to grow at 37 °C to early log phase (OD600 03).
For the antimycobacterial assay, 98 µl of 1:1000-folds
dilution of secondary culture was dispensed into a 96-well
microtiter plate. To each well, 2 µl of the test compound in
DMSO was added to attain a final concentration in the range
of 1–100 µM and allowed to grow at 37 °C for 7 days.
240 µl of sterile water was added to each well of the per-
ipheral rows of 96-well plates to minimize media evapora-
tion during incubation. Bacterial growth was assessed after
7 days of incubation by measuring turbidity at 600 nm

Medicinal Chemistry Research
Molecular docking studies
the atoms of the protein. Glide docking score was used to
determine the best-docked confirmation from the output.
The interactions of these docked conformations were
investigated further using XP visualizer.
Molecular docking studies were carried out using Schrö-
dinger software (Version 2019-1, Schrodinger) installed on
Intel Xenon W 3565 processor and Ubuntu enterprise ver-
sion 14.04 as an operating system. Targeted ligands were
drawn using ChemDraw 18.0. The results of the docking
study were analyzed with the help of XP Visualiser (Ver-
sion 2019-1, Schrödinger).
Molecular docking of the titled compounds
The ENR from M. tuberculosis is one of the critical enzymes
involved in the mycobacterial fatty acid elongation cycle and
has been validated as an effective antimycobacterial target. The
crystal structure of ENR from M. tuberculosis (strain ATCC
25618/H37Rv) (PDB-4TZK) (https://www.rcsb.org/structure/
4TZK) was retrieved from Protein data bank with a resolution
of 1.62 Å. The selected target contains a single-A chain with
269 sequence length residues with one co-crystal ligand (1-
cyclohexyl-n-(3,5)-5-oxopyrrolidine-3-carboxamide) and one
co-factor NAD. A molecular docking study was performed to
understand the putative binding pattern of ligand at the active
site of the target protein. The binding interactions of the sig-
nificantly active and weakly active compounds with the target
protein were analyzed. Before the analysis, the protocol was
validated by checking the RMSD between docked pose and the
X-ray co-crystallized pose.
Ligand preparation
The ligands used as input for docking study were sketched
using ChemDraw software and cleaned up the structures for
bond alignment. Then the ligands were incorporated into the
workstation, and the energy was minimized using OPLS3e
force field in Ligprep (Version 2019-1, Schrödinger). This
minimization helps to assign bond orders, the addition of
hydrogens to the ligands, and conversion of 2D to 3D structure
for further docking studies. The generated output file (best
conformations of the ligands) was further used for docking
studies.
Protein preparation
Validation of the docking protocol
Protein was prepared using the protein preparation wizard
(Version 2019-1, Schrödinger). Hydrogen atom was added to
the proteins, and charges were assigned. Generated Het states
using Epik at pH 7.0 2.0. Pre-processed the protein and
refined, modified the protein by analyzing the workspace;
water molecules and other heteroatoms were examined, non-
significant atoms were excluded from the crystal structure of
the protein. Finally, the protein was minimized by using the
OPLS3e force field. A grid was created by considering the co-
crystallized ligand present in the active site of the selected
target of enoyl-acyl carrier protein reductase (ENR) from M.
tuberculosis (PDB-4TZK).
The precision of the docking study was determined by
finding the lowest energy conformation of the co-crystallized
ligand and resembles an experimental binding mode as
determined by X-ray crystallography. The docking procedure
was authenticated by removing the co-crystallized ligand
from the binding site of the protein and re-docking the same
co-crystallized ligand in the active binding site. The
hydrogen-bonding interaction and RMSD between the
anticipated confirmation and the observed X-ray crystal-
lographic conformation were used for validation. The RMSD
for the targeted protein was found to be 0.5 Å (Fig. 4) and
indicated that the docking protocol could be reliable for
further study to carry out the docking of titled compounds.
Receptor grid generation
A receptor grid was generated around the protein by picking
the inhibitory ligand (X-ray pose of the ligand in the protein).
The centroid of the ligand was selected to create a grid box
around it, and the Vander Waals radius of receptor atoms was
scaled to 1.00 Å with a partial atomic charge of 0.25.
Results and discussion
Target compounds (3a–3p and 4a–4h) were synthesized, as
mentioned in Scheme 1.
Chalcones were prepared by base-catalyzed condensa-
tion of a mixture of the substituted acetophenones and
substituted aldehydes (i.e., substituted naphthaldehydes) in
alcohol. To a solution of substituted acetophenone (2)
(0.1 mol) in ethanol (10 ml), substituted naphthaldehyde (1)
(0.1 mol) was added. To this, aqueous solution potassium
hydroxide (60%, 5 ml) was added gradually with constant
stirring and continued stirring at room temperature for
Docking studies
Docking studies of the significantly active and weakly
active molecules were performed by using the Glide module
in Schrödinger. All docking calculations were performed
using Extra Precision (XP) mode. A scaling factor of 0.8
and a partial atomic charge of less than 0.15 was applied to

Medicinal Chemistry Research
Fig. 4 Overlay view of re-
docked pose of co-crystal ligand
(pink) with its X-ray pose
(white) inside the enoyl-acyl
carrier protein reductase (4TZK)
(RMSD-0.5 Å)
Scheme 1 Synthesis of naphthyl
chalcones and pyrazolines (3a–p
& 4a–h; Nature of substituents,
R, R1 used is given in Table 1)
16–24 h. The separated solid was filtered and washed with
ice-cold water (2 × 50 ml) until the swashing was neutral to
litmus. Crude chalcones (3a–3p) were recrystallized from
ethanol and dried at room temperature. To the solution of
appropriate chalcone (3), hydrazine hydrate (0.02 mol) in
ethanol was added and refluxed for 8–10 h. The progress of
the reaction was monitored using TLC. After completion of
the reaction, the mixture was poured into ice-cold water,
and the crude product was separated and filtered. The crude
products were purified by column chromatography/
recrystallization to get the corresponding pyrazolines in
pure form (4a–4h).
The structures of the synthesized compounds were con-
1
firmed by spectral analysis like FT-IR, H NMR, 13C NMR,
ESI-MASS. IR spectra of chalcones (3a–3p) showed char-
acteristic absorption bands between 1642–1662 cm−1 due to
carbonyl (C=O) stretching. Absorption bands between
2856–2989 cm−1 indicate the presence of aliphatic C–H bonds.
Aromatic C–H stretching was observed in the range of
3002–3089 cm−1. One of the olefinic protons of the chalcone

Medicinal Chemistry Research
Table 2 In vitro antibacterial activity of compounds (II-3a–4h)
appeared as a doublet in the range δ 8.07–8.86 ppm with a J
value of 13–18 Hz, and another olefinic proton appeared as a
doublet or multiplet in the range of δ 7.21–8.03 ppm. The
coupling constant (J) of 12–18 Hz indicates the trans (E)
configuration of the chalcone double bond. All the aromatic
protons appeared in the range of δ 6.8–10.2 ppm. A singlet
observed for one proton in the range of δ 3.72–3.96 ppm
indicates the presence of the –OCH3 group in the compounds
3e–3p.Incompound 3a, the –OH proton appeared as a broad
singlet at δ 12.88 ppm. 13C NMR spectra showed a signal due
to carbonyl (C=O) carbon in the range between δ
189–192 ppm. The ESI-Mass (m/z) spectra of chalcones having
halogens showed [M]+ and [M + 2]+ isotopic peaks. The
chalcones with bromine (3a, 3e, 3g, 3i, 3j, 3m, and 3o)
exhibited [M]+ and [M + 2]+ peaks in 1:1 ratio.
Comp. code
Gram (+) ve organism Gram (−) ve organism
(µg/ml) (µg/ml)
S. aureus B. subtilis E. coli
K. pneumonia
MTCC 96 MTCC 441 MTCC 443 MTCC 109
II-3a
II-3b
II-3c
II-3d
II-3e
II-3f
64
72
18
35
32
16
132
74
33
77
64
32
77
32
72
128
34
28
16
28
72
65
16
18
16
77
32
40
2
33
28
132
66
34
69
38
36
65
35
64
132
65
34
24
36
69
38
48
34
14
69
15
38
4
32
65
24
15
69
77
66
69
II-3g
II-3h
II-3i
135
71
120
74
35
42
II-3j
144
162
155
135
36
149
178
139
120
34
The IR spectra of corresponding pyrazolines (4a–4h) have
shown absorption bands at 3286–3420 cm−1 due to the pre-
sence of –NH (pyrazoline). Absorption bands between
2924–2989 cm−1 indicate the presence of aliphatic C–H
groups, aromatic C–H stretching was observed at
3042–3070 cm−1. Absorption bands observed between
II-3k
II-3l
II-3m
II-3n
II-3o
II-3p
II-4a
II-4b
II-4c
II-4d
II-4e
II-4f
148
38
132
44
1
1540–1589 cm−1 were due to –C=N stretching. H NMR
spectra of pyrazolines showed doublet of doublet in the range
of δ 4.12–5.24 ppm assignable to one of the pyrazoline ring
proton (Hx). Two doublets of doublets in the range of δ
3.32–3.85 & 3.09–3.43 ppm indicate the presence of two
nonequivalent protons of the pyrazoline ring (Hb and Ha). A
singlet for one proton in the range of δ 6.8–7.1 ppm was due to
the presence of pyrazoline –NH. All other aromatic protons
appeared in the range of δ 7.1–10.2 ppm. 13C NMR spectra
have shown signals in the range of δ 40–163 ppm. Pyrazoline
carbons observed between δ 41–56 ppm. In compounds 4c–4h,
signals were observed between δ 54–56 ppm due to the pre-
sence of the –OCH3 group. All other carbons of the aromatic
ring were observed in the region between δ 102–163 ppm. The
mass ESI-MS (m/z) spectra of compounds 4b, 4c, 4d, 4e, 4g
have shown isotopic peaks at [M]+ & [M + 2]+ in the ratio of
1:1 due to the presence of bromine. Compound 4a, 4f and 4h
have shown molecular ion peaks at [M + 1]+.
228
209
120
150
208
68
184
214
128
158
169
64
II-4g
II-4h
Ciprofloxacin
218
209
4
248
185
4
compared to the standard, ciprofloxacin. Among all the
synthesized chalcones and their pyrazoline derivatives,
compound 3d with the 4-methoxy group on phenyl ring
exhibited the highest potency with MIC of 24 and 15 µg/ml
against S. aureus and B. subtilis. However, with the intro-
duction of an additional –OCH3 groups at 2′ and 4′ posi-
tions on naphthalene ring as in compounds 3h and 3l
resulted in a decrease in potency with MIC of 71, 74, and
155, 139 µg/ml against the two same organisms. However,
the potency of compound 3d showed MIC of 74, 66 µg/ml
against Gram −ve bacteria E. coli, and K. pneumoniae, but
the additional methoxy group at 2nd position of naphthalene
ring (3h) resulted in increase in potency by nearly two times
exhibiting MIC of 32 and 36 µg/ml against the two Gram
−ve organisms. Compound 3j, with the 4-methoxy group
on naphthalene ring, 2-hydroxy substituent on phenyl ring
(R = 4-OMe, R′ = 2-OH) showed potency equal to that of
3h (4-OMe and 2′-OMe) against Gram −ve organisms (E.
coli and K. pneumoniae) with MIC of 32 and 35 µg/ml. But
In vitro antibacterial activity
All the synthesized compounds were primarily screened for
the antibacterial activity for two Gram +ve strains and two
Gram −ve strains to ascertain the antibacterial susceptibility
of the synthesized molecules. The results (Table 2) indi-
cated that all compounds showed low antimicrobial activity
against both the tested strains with MIC values in the range
of 14–248 µg/ml when compared to the standard drug
ciprofloxacin. Compound 3d & 4e exhibited significant
activity against Gram +ve strains and Gram −ve organisms
with MIC of 24, 15, and 16, 14 µg/ml, respectively. How-
ever, all the compounds showed less potency when

Medicinal Chemistry Research
Table 3 In vitro antimycobacterial activity of compounds (II-3a–4h)
Table 4 In vitro cytotoxicity of the compounds (II-3a–4h) (IC50–µM)
Comp. code
R
R1
MIC (µM)
Comp. code
MDA-MB-231 (µM SD)
SKOV3 (µM SD)
II-3a
II-3b
II-3c
H
5-Br, 2-OH
2,4-dICl
2-OH
95.8
53.69
49.8
83.6
82.7
92.5
65.2
100
II-3a
II-3b
II-3c
II-3d
II-3e
II-3f
NA
NA
H
36.72 4.28
74.3 14.25
26.8 2.56
41.55 5.68
22.42 2.56
11.9 1.89
41.2 4.56
NA
11.2 1.52
12.9 1.98
17.65 1.86
13.44 1.56
35.74 6.56
34.8 3.52
35.72 4.28
NA
H
II-3d
II-3e
H
4-OMe
5-Br, 2-OH
2-OH
2-OMe
2-OMe
2-OMe
2-OMe
4-OMe
4-OMe
4-OMe
4-OMe
6-OMe
6-OMe
6-OMe
6-OMe
H
II-3f
II-3g
II-3h
II-3i
4-Br
II-3g
II-3h
II-3i
4-OMe
5-Br, 2-OH
2-OH
66.05
70
II-3j
II-3j
37.44 3.56
39.58 4.58
41.45 5.62
38.22 3.98
43.89 4.56
42.75 4.85
22.8 2.86
71.8 14.56
NA
12.02 3.82
34.77 5.85
35.6 6.28
17.82 1.86
11.04 1.45
13.84 1.32
64.4 9.86
12.5 1.85
37.5 5.28
NA
II-3k
II-3l
4-Br
76.8
44.77
45.67
50.99
73.2
42.3
44.65
6.25
42.3
73.3
33.8
42.6
27.7
62.35
5.86
0.3
II-3k
II-3l
4-OMe
5-Br, 2-OH
4-OMe
4-Br
II-3m
II-3n
II-3o
II-3p
II-4a
II-4b
II-4c
II-3m
II-3n
II-3o
II-3p
II-4a
II-4b
II-4c
II-4d
II-4e
II-4f
4-NO2
4-OMe
5-Br, 2-OH
4-Br
H
2-OMe
2-OMe
4-OMe
4-OMe
6-OMe
6-OMe
–
NA
II-4d
II-4e
5-Br-2-OH
4-Br
NA
NA
NA
NA
II-4f
4-OMe
4-Br
164.56 24.56
64.8 12.56
NA
8.52 1.32
34.2 5.62
41.56 7.24
1.20 0.28
II-4g
II-4h
Isoniazid
Rifampicin
II-4g
II-4h
Doxorubicin
5-Br, 2-OH
–
1.38 0.15
–
–
Values represented as (Mean SD, n = 3)
additional 5-bromo substituent as in 3i (R = OMe and R′ =
5-Br, 2-OH) resulted in a decrease in potency by nearly half
with the MIC values of 77 and 65 µg/ml against the two
Gram −ve bacteria. In pyrazoline derivatives (4a–h),
compound 4f with 4 and 4′ dimethoxy substitution has
exhibited the highest potency with 68 and 64 µg/ml against
two Gram +ve bacteria (S. aureus and B. subtilis). Inter-
estingly, the least potent compound 4e (R = 4-OMe & R′ =
4-Br) against Gram +ve bacteria (MIC = 218 & 248 µg/ml)
exhibited highest potency against the Gram −ve bacteria (E.
coli and K. pneumoniae) with MIC values of 16 and 14 µg/
ml respectively. In general, chalcone showed better activity
against Gram +ve bacteria than the pyrazoline showed
greater potency against Gram −ve organisms. For instance,
compound 3k (R = 4-OMe & R′ = 4-Br) showed MIC of
72 & 64 µg/ml, against the two Gram −ve bacteria and its
pyrazoline analog, 4e exhibited grater potency with MIC of
16 and 14 µg/ml against the same organisms.
6.25–100 µM. Among the series, compound 4b with 5-
Bromo-2-hydroxy substitution on phenyl ring possessed
significant activity with MIC of 6.25 µM, comparable to the
standard inh with MIC of 5.86 µM.
In vitro cytotoxicity study
Cytotoxicity studies were performed against MDA-MB-231
& SKOV3 cell lines. All the compounds (3a–4h) exhibited
low cytotoxicity with the IC50 values in the range of
8.52–164.56 µM, and values were presented in Table 4. The
most active compound against Mtb H37R 4b was found to be
nontoxic to MDA-MB-231 (breast cancer cells) and less toxic
to SKOV3 (ovarian cancer cells) with IC50 of 37.5 µM.
In silico prediction of physicochemical and drug-
likeness parameters
Physicochemical properties of a compound play a vital role
in drug absorption, distribution metabolism, and excretion.
All the synthesized molecules were further evaluated for their
drug-likeness behavior through ADME (absorption, dis-
tribution, metabolism, and excretion) properties. Their
molecular weights were <725 Daltons with <6 HBDs and
<20 HBAs (Table 5) fulfilling the criteria of Lipinski’s rule of
five and was found to be in the satisfactory range for
In vitro antimycobacterial activity
The title compounds were also screened for in vitro anti-
mycobacterial activity against H37Rv strain, and results
were presented in Table 3. The results indicated that the
compounds 3a–p and 4a–h possessed significant anti-
mycobacterial activity with MIC in the range of

Medicinal Chemistry Research
Table 5 Predicted in silico
ADMET properties of
compounds (II-3a–4h)
e
Comp. code
M.wta
SASAb
HBDc
HBAd
Log Po/w
log Sf
PCacog
Roth
II-3a
II-3b
II-3c
II-3d
II-3e
II-3f
II-3g
II-3h
II-3i
353.01
327.209
274.02
288.12
383.24
304.339
367.24
318.37
383.04
304.33
367.24
318.37
383.24
318.37
367.236
333.337
302.37
367.24
381.26
397.26
381.2
569.839
570.648
540.87
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
2
1
2
1
1
1
2
1.75
2
5.124
5.474
4.541
4.667
5.197
4.636
5.268
4.778
5.237
4.636
5.268
4.707
5.176
4.702
5.244
3.899
4.567
4.329
5.182
4.555
5.223
4.718
4.168
4.555
−5.622
−5.859
−4.736
−4.816
−5.259
−5.336
−5.501
−4.839
−5.891
−4.489
−5.501
−5.198
−6.08
2308.36
5
4
5
5
6
6
5
6
6
6
5
6
6
6
5
6
1
1
1
2
1
2
1
2
5398.527
2310.791
5330.844
3198.171
3190.689
5709.185
5853.907
2303.857
3190.689
5709.185
3724.134
1604.953
3724.134
3724.849
440.982
1.75
2.75
2.5
572.758
579.994
557.153
591.076
603.21
2.5
2.75
3.5
613.35
2.5
II-3j
II-3k
II-3l
557.153
591.076
622.156
623.362
622.156
613.369
624.862
572.503
570.594
606.316
633.115
605.754
615.613
608.321
633.115
2.5
2.75
3.5
II-3m
II-3n
II-3o
II-3p
II-4a
II-4b
II-4c
II-4d
II-4e
II-4f
II-4g
II-4h
2.5
3.5
−5.198
−5.924
−5.188
−5.542
−5.642
−6.493
−6.371
−6.483
−5.892
−5.284
−6.371
2.75
3.75
2.75
2.75
2.75
3.5
4026.854
1727.006
4027.43
1508.746
4255.892
4015.556
4028.16
2.75
3.5
332.40
381.27
397.27
3.5
3.5
1508.746
aMolecular weight, in Da (range for 95% of drugs: 130–725 Da)
bTotal solvent-accessible volume in cubic angstroms using a probe with a 1.4 Å radius. (500–2000)
cNo: of Hydrogen bonds donated by the molecule (range for 95% of drugs: 0–6)
dNo: of Hydrogen bonds accepted by the molecule (range for 95% of drugs: 2–20)
ePredicted octanol/water partition coefficient log P (acceptable range: –2.0 to 6.5)
fPredicted aqueous solubility; S in mol/L (acceptable range: –6.5 to 0.5)
gApparent Caco-2 permeability (nm/s) (<25 poor, >500 great)
hNumber of nontrivial (not CX3), nonhindered (not alkene, amide, small ring) rotatable bonds. (0–15)
evaluation of the drug-likeness behavior of the molecules. All
other parameters, like octanol/water partition coefficient and
solubility are in between the acceptable range only.
The co-crystallized ligand showed a significant docking
score (−11.20) and binding energy (−67.00) (Table 6). By
keen inspection of 2D and 3D representation of the co-
crystallized ligand (Figs. 5, 6), a hydrogen bond found with
the amino-acid residue TYR-158 (distance 2.78 Å) of protein.
Apart from hydrogen bond interaction, the co-crystallized
ligand also exhibited one aromatic bond interaction with the
amino-acid residue PRO-156 (distance 2.56 Å) and one water
hydrogen-bonding interaction. All these interactions made
the co-crystallized ligand more stable in the active site of the
target protein with a significant docking score. Significantly
active molecule 4b displayed a docking score of −10.50 and
energy of −44.50. The molecule showed a significant
docking score because pyrazole hydrogen offered a hydrogen
bond interaction with the surrounded water molecule (Figs. 7,
8). This hydrogen makes the compound more significant, and
in the in vitro analysis, also the compound exhibited sig-
nificant MIC with 6.25 µM when compared to 5.86 µM
shown by the standard inh.
Apparent Caco-2 permeability of all the compounds
except compound 3p was found to be in the acceptable range.
However, compound 3p showed moderate permeability with
P-CACO-2 permeability of 440.98 (nm/s). The rotatable
bonds for the compounds were in the reasonable range only.
Overall, the predicted physicochemical values indicated that
the maximum number of titled analogs possessed the values
that are well-matched with the optimum range values, and
overall the compounds possessed the drug-likeness behavior.
Molecular docking studies
In order to find out the putative binding mode of significantly
active and weakly active compounds, a molecular docking
study was performed, and the results were given in Table 6.
Before the docking studies, validation of the protein was done
by checking the RMSD and found to be 0.5 Å indicating that
the docking protocol was justified.
Weakly active compound 3h did not show any crucial
hydrogen bond interaction with the surrounded amino-acid

Medicinal Chemistry Research
Table 6 Results of docking
studies and the amino-acid
residues involved in the
interactions
Comp. code
Hydrogen bond
Aromatic bond
Glide score
Glide energy
Co-crystal ligand (PDB-4TZK)
Significantly active molecule-II-4b
Weakly active molecule-II-3h
TYR-158 H2O
PRO-156
–
−11.20
−10.50
−6.74
−67.00
−44.50
−42.50
H2O
–
Pro-156
Fig. 5 3D representation of the
co-crystal ligand in the active
site of the target 4TZK
Fig. 6 2D representation of the
co-crystal ligand in the active
site of the target 4TXK
Fig. 7 3D representation of the
significantly active compound
4b in the active site of the
target 4TZK

Medicinal Chemistry Research
Fig. 8 2D representation of the
significantly active compound
4b in the active site of the
target 4TZK
Fig. 9 3D representation of the
weakly active compound 3 h in
the active site of the target 4TZK
Fig. 10 2D representation of the
weakly active compound 3 h in
the active site of the target 4TZK
residues. However, it revealed an aromatic bond interaction
with the amino-acid residue PRO-156 and displayed
the docking score of −6.7 and docking energy of −42.50
(Figs. 9, 10). Due to a lack of hydrogen bond interaction
with the target protein, the compound 3h might have shown
less in vitro activity against M. tuberculosis with MIC of
100 µM.
Conclusion
A series of naphthyl chalcones and their pyrazoline deriva-
tives were synthesized by standard protocol. All the synthe-
sized compounds have shown significant antibacterial
activity. Among the series, compound 4b found to exhibit
potent activity against M. tuberculosis with the MIC of

Medicinal Chemistry Research
6.28 µM, and in docking studies, it revealed good hydrogen
bond interaction with surrounded amino-acid residues. All the
compounds in the series have shown minimal to moderate
cytotoxicity; however, compound 4b was found to be non-
toxic to MDA-MB-231 cell lines. In summary, our results on
the biological screening and in silico studies of the synthe-
sized compounds offered an ethical framework that may lead
to the discovery of new potent antitubercular agents.
with antitubercular activity. Eur J Med Chem 137:126–138.
https://doi.org/10.1016/j.ejmech.2017.05.026
Hans RH, Guantai EM, Lategan C et al. (2010) Synthesis, antimalarial and
antitubercular activity of acetylenic chalcones. Bioorg Med Chem
Lett 20:942–944. https://doi.org/10.1016/j.bmcl.2009.12.062
He X, Alian A, Stroud R, Montellano PRO De (2006) Pyrrolidine
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biological evaluation of novel chalcones as anti bacterial agents.
Arab J Chem 10:S2890–S2895. https://doi.org/10.1016/j.arabjc.
2013.11.018
Acknowledgements One of the authors thankful to the Central Mass
Division, IICT, Hyderabad for providing mass spectrometry, Mole-
cular Biology Department for providing the antimycobacterial activity.
BKK and SM thankful to the Department of Biotechnology, Indo-
Spain, New Delhi (Ref. No: BT/IN/Spain/39/SM/2017-2018).
Kumar D, Ahmad I, Shukla A, Khan F (2014) QSAR and docking
studies on chalcone derivatives for antitubercular activity against
M. tuberculosis H 37 Rv. J Chemom 1–24. https://doi.org/10.
1002/cem.2606.
Kumar RK, Sharma RSK, Kumar DR et al. (2016) ISSN 0975-413X
CODEN (USA): PCHHAX characterization, synthesis and bio-
logical evaluation of naphthalene based piperazines as anti bac-
terial agents. Der Pharma Chem 8:374–379
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
Lin Y, Zhou Y, Flavin MT et al. (2002) Chalcones and flavonoids as
anti-tuberculosis agents. Bioorg Med Chem 10:2795–2802
Lopes T, Ventura B, Calixto SD et al. (2015) Antimycobacterial and
anti-inflammatory activities of substituted chalcones focusing on
an anti-tuberculosis dual treatment approach. Molecules
20:8072–8093. https://doi.org/10.3390/molecules20058072
Malothu N, Bhandaru JS, Kulandaivelu U et al. (2015) Synthesis,
in vitro antimycobacterial evaluation and docking studies of some
new 5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4
(3H)-one Schiff Bases. Bioorg Med Chem Lett 4. https://doi.org/
10.1016/j.bmcl.2015.12.083.
Publisher’s note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.
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