Journal of Chemistry

Volume 2013 (2013), Article ID 542973, 4 pages

http://dx.doi.org/10.1155/2013/542973

Research Article

Green Synthesis and In Vitro Biological Evaluation of Heteroaryl Chalcones and Pyrazolines of Medicinal Interest

Vishal Banewar

Department of Chemistry, Government Vidarbha Institute of Science & Humanities, Amravati 444 604, India

Received 28 May 2013; Revised 11 September 2013; Accepted 19 September 2013

Academic Editor: Naoki Haraguchi

Copyright © 2013 Vishal Banewar. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

Pyrazolines are well known and important nitrogen containing 5-membered heterocyclic compounds. In the present investigation, a series of various heteroaryl chalcones and pyrazolines were synthesized by condensing formylquinolines with diverse ketones. The newly synthesized 2-pyrazolines were characterized on the basis of elemental analysis and spectroscopic data. All of the newly synthesized target compounds were selected by the NCI for in vitro biological evaluation. These active compounds exhibited broad spectrum of various biological activities. Most of the compounds showed potent activity.

1. Introduction

Due to the rapid development of bacterial resistance to antibacterial agents, it is vital to discover novel scaffold for the design and synthesis of new antibacterial agents to help in the battle against pathogenic microorganisms [1–3]. Much research has been carried out with the aim to discover the therapeutic values of thiazole derivatives. A large number of substituted thiazole derivatives were prepared and tested for variety of biological properties [4] such as antimicrobial activity [5, 6]. Amongst the wide variety of heterocycles that have been explored for developing pharmaceutically important molecules such as cyanopyridines [7–9] and triazolopyridines [10–12] have played an important role in medicinal chemistry. They are reported to possess a broad spectrum of biological activity such as potential cardiovascular agents, antiviral [13], CNS depressant [14, 15], bactericidal [16, 17], and ulcer inhibitors [18, 19]. Furthermore, researchers have also revealed that Phenothiazine derivatives constitute an important class of compounds possessing diverse type of biological properties including antiviral [20–22], antiparasitic [23], antiparkinsonian [24, 25], anticonvulsant [26], antihistaminic [27], and anthelmintic [28] properties.

Encouraged by the literature reports and to assess the pharmacological profile of such class of compounds and in continuation with the wok related to the synthesis, spectral studies, and biological properties of pyrazolines, herein we report the synthesis of some novel pyrazolines and then their antibacterial and antifungal activities in the present study.

2. Materials and Methods

Melting points were determined by open capillary and are uncorrected. The purity of the compounds was checked using precoated TLC plates (MERCK, 60F) using chloroform : methanol : water (1 : 4 : 5) solvent system. The plates were visualized under UV light (254 nm). IR spectra were recorded using KBr on Shimadzu FTIR model 8000 spectrophotometer, and 1H NMR spectra were recorded in DMSO on a BRUKER FT-NMR instrument using TMS as an internal standard.

3. Experimental Studies

3.1. General Methods for the Synthesis of Chalcones

The three precursors, 2-chloroquinoline-3-carbaldehyde, 2-chloro-6-nitroquinoline-3-carbaldehyde, and 6-bromo-2-chloroquinoline-3-carbaldehyde, were prepared by the reported method in [29]. Synthesis of the compounds (1a–d, 2a–d, and 3a–d) (Scheme 1), was based on Claisen-Schmidt condensation [30–32].

Scheme 1

A mixture of quinoline-3-carbaldehyde (0.01 mol), ketone a–d (0.10 mol), and aq. NaOH (4 mL, 10%) in methanol (50 mL) was refluxed for 2 h, and the reaction mixture was then kept at 0°C (24 h). Subsequently, it was poured onto ice cold water (200 mL). The precipitates were collected by filtration and washed with cold water followed by cold MeOH. The resulting chalcones were recrystallized from CHCl₃ and obtained in good yield (60–83%) (Table 1). Spectral data (IR, 1H-NMR, and MS) of all the newly synthesized chalcones were in full agreement with the proposed structures.

Table 1: Physical properties of synthesized compounds.

Compound
–R
(a–d)
Molecular formula
Yield %
Elemental analysis

C
H
O
N
Cl
Br

1a
H
a
C₁₅H₁₂ClNO
83
69.91 (69.27)
4.69 (4.71)
6.21 (5.85)
5.43 (5.92)
13.76 (14.25)

1b
H
b
C₁₆H₁₄ClNO
75
70.72 (70.54)
5.19 (5.76)
5.89 (5.34)
5.15 (5.47)
13.05 (12.89)

1c
H
c
C₁₈H₁₁ClN₂O₃
71
63.82 (62.96)
3.27 (3.75)
14.17 (14.76)
8.27 (7.75)
10.47 (10.78)

1d
H
d
C₁₈H₁₂ClNO
62
73.60 (73.10)
4.12 (4.37)
5.45 (5.20)
4.77 (5.25)
12.07 (12.08)

2a
NO₂
a
C₁₅H₁₂N₂O₃
75
67.16 (67.25)
4.51 (4.25)
17.89 (17.75)
10.44 (10.75)

2b
NO₂
b
C₁₆H₁₄N₂O₃
80
68.07 (68.05)
5.00 (5.10)
17.00 (17.06)
9.92 (9.79)

2c
NO₂
c
C₁₈H₁₁N₃O₅
63
61.89 (61.78)
3.17 (3.08)
22.90 (22.76)
12.03 (12.38)

2d
NO₂
d
C₁₈H₁₂N₂O₃
64
71.05 (71.25)
3.97 (3.67)
15.77 (15.96)
9.21 (9.12)

3a
Br
a
C₁₅H₁₂BrNO
64
59.62 (59.61)
4.00 (4.10)
5.29 (5.31)
4.64 (4.61)

26.44 (26.37)

3b
Br
b
C₁₆H₁₄BrNO
60
60.78 (60.67)
4.46 (4.67)
5.06 (5.10)
4.43 (4.12)

25.27 (25.44)

3c
Br
c
C₁₈H₁₁BrN₂O₃
62
56.42 (56.12)
2.89 (2.87)
12.53 (12.23)
7.31 (7.45)

20.85 (21.33)

3d
Br
d
C₁₈H₁₂BrNO
82
63.92 (63.90)
3.58 (3.60)
4.73 (4.65)
4.14 (4.20)

23.63 (23.65)

2-(2-Chloroquinoline-3-yl-methylene)-cyclopentanone. IR (KBr) cm⁻¹: 1648 (C=O), 1592 (C=C). 1H-NMR (CDCl₃) δ: 1.44 (2H, m, –CH₂), 1.96 (2H, t, –CH₂), 2.94 (2H, t, –CH₂), 7.26 (1H, s, =CH-ylene), 7.43–8.33 (5H, quinoline Ar-H). MS (m/z): 257 (M+, 100%).

2-(2-Chloroquinoline-3-yl-methylene)-cyclohexanone. IR (KBr) cm⁻¹: 1656 (C=O), 1562 (C=C). 1H-NMR (CDCl₃) δ: 1.61 (2H, m, –CH₂), 1.96 (2H, t, –CH₂), 2.45 (2H, t, –CH₂), 3.12 (2H, s, –CH₂), 6.27 (1H, s, =CH-ylene), 7.43–8.33 (5H, quinoline Ar-H). MS (m/z): 271 (M+, 100%).

3-(2-Chloroquinoline-3-yl)-1-(4-nitrophenyl)-propenone. IR (KBr) cm⁻¹: 1644 (C=O), 1542 (C=C). 1H-NMR (CDCl₃) δ: 8.07–8.38 (4H, Ar-H), 7.56 (1H, d, ), 7.90 (1H, d, ), 7.13–8.50 (5H, quinoline Ar-H). MS (m/z): 338 (M+, 100%).

3-(2-Chloroquinoline-3-yl)-1-phenyl Propenone. IR (KBr) cm⁻¹: 1654 (C=O), 1581 (C=C). 1H-NMR (CDCl₃) δ:  7.45–7.81 (5H, Ar-H), 7.60 (1H, d, ), 7.82 (1H, d, ), 7.23–7.92 (5H, quinoline Ar-H). MS (m/z): 293 (M+, 100%).

2-(2-Nitroquinoline-3-yl-methylene)-cyclopentanone. IR (KBr) cm⁻¹: 1650 (C=O), 1560 (C=C). 1H-NMR (CDCl₃) δ: 1.41 (2H, m, –CH₂), 1.85 (2H, t, –CH₂), 2.73 (2H, t, –CH₂), 7.51 (1H, s, =CH-ylene), 7.70–8.82 (5H, quinoline Ar-H). MS (m/z): 268 (M+, 100%).

2-(2-Nitroquinoline-3-yl-methylene)-cyclohexanone. IR (KBr) cm⁻¹: 1656 (C=O), 1553 (C=C). 1H-NMR (CDCl₃) δ: 1.53 (2H, m, –CH₂), 1.87 (2H, t, –CH₂), 2.82 (2H, t, –CH₂), 3.05 (2H, s, –CH₂), 6.61 (1H, s, =CH-ylene), 7.41–8.27 (5H, quinoline Ar-H). MS (m/z): 282 (M+, 100%).

1-(4-Nitrophenyl)-3-(2-nitroquinolin-3-yl)-propenone. IR (KBr) cm⁻¹: 1654 (C=O), 1548 (C=C). 1H-NMR (CDCl₃) δ: 8.21–8.48 (4H, Ar-H), 7.51 (1H, d, ), 7.85 (1H, d, ), 7.11–8.51 (5H, quinoline Ar-H). MS (m/z): 349 (M+, 100%).

3-(2-Nitroquinolin-3-yl)-1-phenyl Propenone. IR (KBr) cm⁻¹: 1656 (C=O), 1587 (C=C). 1H-NMR (CDCl₃) δ: 7.21–7.73 (5H, Ar-H), 7.51 (1H, d, ), 7.90 (1H, d, ), 7.29–7.76 (5H, quinoline Ar-H). MS (m/z): 304 (M+, 100%).

2-(2-Bromo-quinoline-3-yl-methylene)-cyclopentanone. IR (KBr) cm⁻¹: 1665 (C=O), 1590 (C=C). 1H-NMR (CDCl₃) δ: 1.46 (2H, m, –CH₂), 1.64 (2H, t, –CH₂), 2.41 (2H, t, –CH₂), 7.50 (1H, s, =CH-ylene), 7.48–8.60 (5H, quinoline Ar-H). MS (m/z): 301 (M+, 100%).

2-(2-Bromo-quinoline-3-yl-methylene)-cyclohexanone. IR (KBr) cm⁻¹: 1656 (C=O), 1553 (C=C). 1H-NMR (CDCl₃) δ: 1.60 (2H, m, –CH₂), 1.95 (2H, t, –CH₂), 2.44 (2H, t, –CH₂), 3.11 (2H, s, –CH₂), 6.26 (1H, s, =CH-ylene), 7.48–8.54 (5H, quinoline Ar-H). MS (m/z): 315 (M+, 100%).

3-(2-Bromoquinolin-3-yl)-1-(4-nitrophenyl)-propenone. IR (KBr) cm⁻¹: 1634 (C=O), 1556 (C=C). 1H-NMR (CDCl₃) δ: 8.01–8.24 (4H, Ar-H), 7.58 (1H, d, ), 7.92 (1H, d, ), 7.45–8.16 (5H, quinoline Ar-H). MS (m/z): 382 (M+, 100%).

3-(2-Bromoquinolin-3-yl)-1-phenyl Propenone. IR (KBr) cm⁻¹: 1645 (C=O), 1556 (C=C). 1H-NMR (CDCl₃) δ: 7.42–7.84 (5H, Ar-H), 7.43 (1H, d, ), 7.76 (1H, d, ), 7.65–7.86 (5H, quinoline Ar-H). MS (m/z): 338 (M+, 100%).

4. Antibacterial Screening

Antimicrobial activity was carried out by cup-plate agar diffusion method at a concentration of 50 μg/mL in solvent DMF. The purified products were screened for their antibacterial activity. The nutrient agar slant prepared by the usual method was incubated at 37 ± 5°C for 24 h. The zone of inhibition was measured in mm. The antimicrobial activity of the synthesized compounds was compared with standard drugs.

All series of compounds nearly exhibit the same antimicrobial activities against all the four bacterial strains, that is, B. subtilis, B. pumilius, E. coli, and S. aureus (Table 2). Among all series of compounds, 1a, 2b, and 3c exhibit strong antibacterial activity. Introduction of aromatic ketone increases the activity against all microorganisms. It is further increased by the incorporation of NO₂ group at the fourth position of aromatic ketone. Amongst the aliphatic ketone, five membered compounds show decrease in activity (1a–1c) in comparison with six membered compounds (2b–2d). In general, aromatic introduction in the compounds enhances the activity, while activity is suppressed by introduction of aliphatic group in the compounds.

Table 2: Antimicrobial activity of synthesized compounds.

Zone (mm) (50 μg)
Compounds

1a
1b
1c
1d
2a
2b
2c
2d
3a
3b
3c
3d

B. subtilis
4
5
5
6
4
6
5
5
5
4
6
5

B. pumilus
4
5
5
5
—
5
5
—
5
5
7
5

E. coli
4
4
4
4
4
4
4
4
4
—
4
5

S. aureus
—
—
—
5
—
5
4
6
5
4
4
6

5. Antifungal Screening

The antifungal activities of the compounds 1a–d, 2a–d, and 3a–d have been assayed at the concentration of 200 μg/disc assays against four plants pathogenic and moulds fungi. The inhibitory effects of compounds against these organisms are given in Table 3. The screening results indicate that the compound shows good to moderate antifungal activities to the tested fungi against Curvularia eryostides, Drecheslera tetrameda, Fusarium cicerg, and Bipolaris sorokenia.

Table 3: Antifungal activity of synthesized compounds.

Zone (mm)
Compounds

1a
1b
1c
1d
2a
2b
2c
2d
3a
3b
3c
3d

Curvularia  eragrostidis
10
08
09
16
08
06
12
09
10
12
08
10

Drechslera  tetramera
12
14
12
02
12
08
10
13
08
10
07
11

Fusarium  ciceri
14
10
11
12
10
12
12
12
15
11
15
16

Bipolaris  sorokiniana
07
14
06
16
06
06
16
07
12
13
16
05

All the compounds show promising antifungal activity against all fungi except Bipolaris sorokiniana (Table 3). All the compounds show strong activity against Drechslera tetramera and Fusarium ciceri compared with that of the other two fungi. As in the case of antimicrobial, introduction of aromatic group enhances the activity of 2c, 2d, 3c, and 3d. Introduction of NO₂ group at fourth position increases the activity of 1c, 2c, and 3c.

Introduction of electron withdrawing group shows remarkable difference in biological activity (both antimicrobial and antifungal).

No systematic change has been observed in antibacterial and antifungal activity for the rest of the compounds.

6. Conclusion

All the synthesized compounds were characterized with their physical and spectral data. The antifungal and antibacterial screening of the synthesized pyrazolines were found to be active.

This research study reports the successful synthesis of new heteroaryl pyrazoline. It also reports antimicrobial and antifungal studies of synthesized compounds. The biological study revealed that compounds showed moderate to good activity.

Acknowledgments

The author is thankful to the Department of Chemistry, Government Vidarbha Institute of Science & Humanities, Amravati, Maharashtra, India, and Director of Garware Lab, Department of Chemistry, Pune University, Pune, for 1H NMR spectral characterization.

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