1-[3/-(SUBSTITUTED PHENYL) -5/- (AMINO PYRIMIDINE)]- 3- (4/-NITRO PHENYL) 5-(SUBSTITUTED PHENYL)- 2-PYRAZOLINES: SYNTHESIS, CHRACTERISATION AND ANTIMICROBIAL SCREENING
HTML Full Text1-[3/-(SUBSTITUTED PHENYL) -5/- (AMINO PYRIMIDINE)]- 3- (4/-NITRO PHENYL) 5-(SUBSTITUTED PHENYL)- 2-PYRAZOLINES: SYNTHESIS, CHRACTERISATION AND ANTIMICROBIAL SCREENING
Y. A. Hatwar
Department of Chemistry, Rajiv Gandhi College of Engineering, Research and Technology, Chandrapur, Gondwana University - 442403, Maharashtra, India.
ABSTRACT: In the present study eight novel 2-pyrazoline - amino pyrimidine hybrids have been synthesized in order to search new chemical entities with increased pharmacological properties. The targeted analogues were synthesized in four steps; Claisen-schmidt condensation of 4-nitro acetophenone with different benzaldehydes in basic medium to yield precursor chalcone which was cyclised using hydrazine hydrates and acetic acid to form 1-acetyl-2-pyrazoline. These were condensed with substituted benzaldehydes to give corresponding pyrazolyl chalcones, which were cyclised using guanidine carbonate to obtain 2-pyrazoline-amino pyrimidine hybrids. All the synthesized compounds were characterized by elemental and spectral (1H and 13C NMR, FTIR and Mass) analysis. All the compounds have been screened for their anti-bacterial activity against gram positive bacteria (Bacillus substilis, Streptococcus aureus), gram negative bacteria (Pseudomonas aeruginosa, Escherichia coli) and antifungal activity against Aspergillus niger comparable to reference standard ciprofloxacin and fluconazole by agar-well diffusion method. All compounds 4(a-h) exhibited moderate to high activity and showed more pronounced antibacterial activity than antifungal activity. 4h showed dual effect antibacterial as well as antifungal agent.
Keywords: |
Heterocycles, 2-pyrazolines, Chalcones, Amino pyrimidines, Antifungal, Antibacterial
INTRODUCTION: The development of new antimicrobial agents can be partially ascribed both to the increasing emergence of bacterial resistance to antibiotic therapy and to newly emerging pathogens 1. To overcome this rapid development of drug resistance, new agents should preferably consist of chemical characteristics that clearly differ from those of existing agents.
In the process of drug designing to search for new leads is comprises of the synthesis of novel molecules, which resembles the existing biologically active molecules by virtue of the presence of critical structural features. Nitrogen containing heterocycles act as highly functionalized scaffolds in medicinal chemistry and drug discovery. Heterocycles, containing 2-nitrogen atoms, pyrazoline and pyrimidine derivatives have drawn considerable attention of the researcher due to their high therapeutic values.
Pyarazoline derivatives have been reported to possess broad spectrum of pharmacological activities such as antidepressant 2, anticonvulsant activity 3, anticancer 4 - 8, antitubercular 9, 10, anti-inflammatory 11, 12, anti-coagulant 13, anti-amoebic 14, antimalerial 15, 16, antibacterial 17, anti-microbial 10, 18, analgesic 19, cytotoxic 20 - 21, pesticide 22 and pesticidal and fungicidal activities 23. Pyrimidine derivatives exhibited various biological activities such as anti-proliferative 24, anticancer 25, 26, anti-hypertensive 27, antioxidant 28, 29, antiviral 30, anti-inflammatory and analgesic activities 31, 32. Certain pyrimidine derivatives play a significant role in several biological processes and show, anti-leishmanial activities 33 and CNS depressant properties 34. On the basis of above mentioned importance of pyrazolines and pyrimidines efforts have been made to design and synthesize mutual prodrugs containing these nuclei to produce synergistic antimicrobial activity. The synthesized compounds have been subjected for in vitro antimicrobial activity against some selected bacterial and fungal strains.
MATERIALS AND METHODS: All the chemicals and solvents of Sigma Aldrich were AR grade and used without further purification. Melting Points were determined in open glass capillaries in an electrical melting point apparatus and are uncorrected. Purity was checked by thin layer chromatography on silica gel G plates using UV light as visualizing agent. IR spectra were recorded on FTIR spectrophotometer Shimadzu 8201 PC (4000 - 400 cm-1) using KBr pallet technique. 1H and 13C NMR spectra were recorded on Bruker Avance-II 400 MHz NMR spectrometer using DMSO-d6 as a solvent and tetra methyl silane as internal standard. Mass spectra were recorded on Waters, Q-TOF, Micromass (LC-MS spectrometer) and Elemental analyser used for CHN analysis. All the synthesized compounds were screened for their antibacterial and antifungal activity using agar-well diffusion method.
General Procedure for Preparation of Compounds:
1) Synthesis of 1-(4/-nitro phenyl)-3-(substituted phenyl) prop-2-en-1-one (1): Equimolar quantity of 4-nitro acetophenone (0.01 mole) and aromatic aldehydes (0.01 mole) were dissolved in minimum amount of alcohol below 25 °C. NaOH (10 ml, 40%) was added drop wise. The reaction mixture was stirred vigorously for 2 - 3 hours and neutralized with concentrated hydrochloric acid. The solid obtained was recrystallized with suitable solvent. Similarly other compounds were also prepared.
2) Synthesis of 1-acetyl-3-(4/-nitro phenyl)-5-(substituted phenyl)-2-pyrazolines (2): A mixture of chalcones (10 mmoles), 99% Hydrazine hydrate (50 mmole) and glacial acetic acid (60 ml) was refluxed for 3 - 6 hour in water bath, then poured on to crushed ice. The resulting solid was washed and crystallized from ethanol to obtained the 2-pyrazoline derivatives.
3) Synthesis of 1-(substituted chalcone)-3-(4/-nitro phenyl)-5-(substituted phenyl)-2-pyrazolines (3): Equimolar quantity of synthesized 1-acetyl-3-(4/-nitro phenyl)-5-(substituted phenyl)-2-pyrazolines (0.01 mole) and different aromatic aldehydes (0.01 mole) were dissolved in minimum amount of alcohol with the dropwise addition of NaOH solution (10 ml, 40%). The reaction mixture was stirred vigorously for 2 - 3 hours and neutralized with concentrated Hydrochloric Acid. The solid obtained was washed with cold water and recrystalised with suitable solvent.
4) Synthesis of 1-(3/-substituted phenyl-5/-amino pyrimidine)- 3- (4/-nitro phenyl)-5 -(substituted phenyl)-2-pyrazolines [4(a-h)]: A mixture of 1-(substituted chalcone)- 3- (4/-nitro phenyl)- 5-(substituted phenyl)- 2- pyrazoline (0.01 mole), guanidine carbonate (0.01 mole) and NaOH (0.01 mole, 0.4 g) was dissolved in DMF (40 ml). The reaction mixture was stirred and refluxed for 5 hours on water bath then poured on to crushed ice. The solid obtained was washed with cold water and purified by recrystalisation from ethanol.
TABLE 1: PHYSICOCHEMICAL CHARACTERIZATION DATA OF SYNTHESIZED COMPOUNDS 4(a-h)
Compound ID | R1 | R2 | Molecular Formula | Molecular Weight | M. P. °C | Yield % | Analysis | ||
C% | H% | N% | |||||||
4a | 4N(CH3)2 | 4-OH | C27H25N7O3 | 495 | 132 | 66 | 65.45
65.44 |
5.05
5.09 |
19.80
19.88 |
4b | 4N(CH3)2 | 4-OCH3 | C28H27N7O3 | 509 | 147 | 70 | 66.01
66.10 |
5.31
5.39 |
19.25
19.32 |
4c | 4N(CH3)2 | 3- NO2 | C27H24N8O4 | 524 | 125 | 71 | 61.83
61.79 |
4.58
4.65 |
21.37
21.39 |
4d | 4N(CH3)2 | 4-N(CH3)2 | C29H30N8O2 | 522 | 110 | 76 | 66.67
66.64 |
5.75
5.78 |
21.46
21.51 |
4e | 3-NO2 | 4-OH | C25H19N7O5 | 497 | 109 | 82 | 60.36
60.30 |
3.82
3.90 |
19.72
19.66 |
4f | 3-NO2 | 4-OCH3 | C26H21N7O5 | 511 | 94 | 76 | 61.06
61.11 |
4.11
4.09 |
19.18
19.21 |
4g | 3-NO2 | 3- NO2 | C25H18N8O6 | 526 | 88 | 67 | 57.03
57.10 |
3.42
3.49 |
21.29
21.22 |
4h | 4-OH | 2,4-(Cl)2 | C25H18N6O3Cl2 | 521 | 135 | 58 | 57.69
57.64 |
3.46
3.44 |
16.15
16.19 |
TABLE 2: THE IN VITRO ANTIMICROBIAL ACTIVITY OF COMPOUNDS, 4(a-h)
S. no. | Derivative | Diameter of zone of inhibition (mm) for organism | ||||
Bacterial Strains | Fungal strains | |||||
Gram negative | Gram positive | |||||
E. coli | P. Aeruginosa | S. Aurius | B. Subtilis | A. niger | ||
1 | 4a | 16 | 20 | 20 | 14 | 19 |
2 | 4b | 17 | 19 | 18 | 15 | 17 |
3 | 4c | 17 | 20 | 19 | 16 | 17 |
4 | 4d | 16 | 22 | 22 | 15 | 19 |
5 | 4e | 15 | 20 | 21 | 18 | 18 |
6 | 4f | 14 | 20 | 19 | 16 | 16 |
7 | 4g | 15 | 19 | 18 | 16 | 17 |
8 | 4h | 21 | 21 | 21 | 20 | 23 |
9 | Ciprofloxacin | 48 | 51 | 41 | 40 | -- |
10 | Fluconazole | -- | -- | -- | -- | 40 |
Diameter of inhibition zone measured in mm, inhibition zone measured including well diameter. 0 - 12 = resistant, 13 - 18 = moderately active, above 19 = highly active.
FIG. 1: COMPARISON OF DIAMETER OF ZONE OF INHIBITION OF 4(a-h) WITH STANDARD “CIPROFLOXACIN” AND “FLUCONAZOLE”
The spectral data of synthesized compound 4(a-h):
4a: 1-[3/-(4//-hydroxy phenyl)-5/-amino pyrimidine]-3-(4/-nitro phenyl)-5-(4/-dimethyl amino phenyl)-2-pyrazoline; IR (KBr, γmax, cm-1): 3533.21, 3415.83 (NH2), 3084.19, 3038.30 (Ar-H), 2903.23, 2830.22 (C-H, asymmetric and symmetric stretching), 1662.12,1599.25 (C=N), 1551.42 (C=C), 1530.81, 1372.42 (Ar-NO2), 1160.28 (C-N); 1H NMR (DMSO) 400 MHz, δ ppm: 9.67 (s, 1H,-OH), 8.19-6.71 (m,13H, Ar-H), 5.62-5.59 (dd, 1H, C5 pyrazoline), 4.67 (s,2H,-NH2), 3.70-3.63 (dd, 1H, C4cis pyrazoline), 3.18-3.14 (dd,1H,C4trans pyrazoline), 3.03 (s, 6H, -N(CH3)2); 13C NMR (DMSO) 100 MHz, δ ppm: 165.20 (C1 pyrimidine), 162.60 (C5 pyrimidine), 158.25 (C3 pyrimidine), 152.43 (C3 pyrazoline), 160.16 - 110.20 (18C, phenyl ring), 92.98 (C2 pyrimidine), 59.61 (C5 pyrazoline), 41.08 (C4 pyrazoline), 40.03 (N(CH3)2); Mass Spectra: MS: m/z 495 (M+).
4b: 1-[3/-(4//-methoxy phenyl)-5/-amino pyrimidine]-3-(4/-nitro phenyl)-5-(4/-dimethyl amino phenyl)-2-pyrazoline; IR (KBr, γmax, cm-1): 3514.26, 3421.92 (NH2), 3089.91, 3033.18 (Ar-H), 2938.60, 2841.70 (C-H, asymmetric and symmetric stretching), 1663.92, 1598.35 (C=N), 1549.21 (C=C), 1535.71, 1372.14 (Ar-NO2), 1155.12 (C-N); 1H NMR (DMSO) 400 MHz, δ ppm: 8.22-6.66(m, 13H, Ar-H), 5.61-5.54 (dd, 1H, C5 pyrazoline), 4.38 (s, 2H, -NH2), 3.69-3.62 (dd, 1H, C4cis pyrazoline), 3.21-3.16 (dd, 1H, C4trans pyrazoline), 3.05 (s, 6H, -N(CH3)2); 13C NMR (DMSO) 100 MHz, δ ppm: 164.98 (C1 pyrimidine), 162.69 (C5 pyrimidine), 158.33 (C3 pyrimidine), 151.98 (C3 pyrazoline), 158.33 – 110.60 (18C, phenyl ring), 93.07 (C2 pyrimidine), 59.72 (C5 pyrazoline), 55.32 (1C, -OCH3), 41.09 (C4 pyrazoline), 40.23 (N(CH3)2); Mass Spectra: MS: m/z 509 (M+).
4c: 1-[3/-(3//-nitro phenyl)-5/-amino pyrimidine]-3-(4/-nitro phenyl)-5-(4/-dimethyl amino phenyl)-2-pyrazoline; IR (KBr, γmax, cm-1): 3532.45, 3406.88 (NH2), 3086.20, 3049.28 (Ar-H), 2961.19, 2865.20 (C-H, asymmetric and symmetric stretching), 1663.72,1599.46 (C=N), 1551.52 (C=C), 1540.48, 1371.92 (Ar-NO2), 1158.31 (C-N); 1H NMR (DMSO) 400 MHz, δ ppm: 8.65-6.68 (m, 13H, Ar-H), 5.64-5.58 (dd, 1H, C5 pyrazoline), 4.40 (s, 2H, -NH2), 3.68-3.60 (dd, 1H, C4cis pyrazoline), 3.23-3.19 (dd, 1H, C4trans pyrazoline), 3.04 (s, 6H, -N(CH3)2); 13C NMR (DMSO) 100 MHz, δ ppm: 165.04 (C1 pyrimidine), 162.60 (C5 pyrimidine), 157.87 (C3 pyrimidine), 152.08 (C3 pyrazoline), 151.48 – 110.55 (18C, phenyl ring), 93.67 (C2 pyrimidine), 59.80 (C5 pyrazoline), 41.20 (C4 pyrazoline), 40.09 (N(CH3)2); Mass Spectra: MS: m/z 524 (M+).
4d: 1-[3/-(4//-dimethyl amino phenyl)- 5/- amino pyrimidine]- 3- (4/- nitro phenyl)- 5- (4/-dimethyl amino phenyl)-2-pyrazoline; IR (KBr, γmax, cm-1): 3549.43, 3415.78 (NH2), 3085.90, 3041.21 (Ar-H), 2921.62, 2862.38 (C-H, asymmetric and symmetric stretching), 1663.62, 1598.64 (C=N), 1554.61 (C=C), 1532.81, 1371.62 (Ar-NO2), 1161.44 (C-N); 1H NMR (DMSO) 400 MHz, δ ppm: 8.23-6.72 (m, 13H, Ar-H), 5.66-5.62 (dd, 1H, C5 pyrazoline), 4.52 (s, 2H, -NH2), 3.66-3.61 (dd, 1H, C4cis pyrazoline), 3.20-3.15 (dd, 1H, C4trans pyrazoline), 3.04 (s, 12H, [-N(CH3)2]2); 13C NMR (DMSO) 100 MHz, δ ppm: 165.10 (C1 pyrimidine), 162.58 (C5 pyrimidine), 158.01 (C3 pyrimidine), 152.18 (C3 pyrazoline), 151.60-110.62 (18C, phenyl ring), 92.78 (C2 pyrimidine), 59.77 (C5 pyrazoline), 41.10 (C4 pyrazoline), 40.23 (N(CH3)2); Mass Spectra: MS: m/z 522 (M+).
4e: 1-[3/-(4//-hydroxy phenyl)-5/-amino pyrimidine] -3-(4/-nitro phenyl)-5-(3/-nitro phenyl)-2-pyrazoline; IR (KBr, γmax, cm-1): 3522.28, 3423.92 (NH2), 3269.51 (Ar-OH), 3086.23, 3034.91 (Ar-H), 1662.79,1596.92 (C=N), 1562.11 (C=C), 1535.82, 1369.19 (Ar-NO2), 1163.40 (C-N); 1H NMR (DMSO) 400 MHz, δ ppm: 8.86 (s, 1H,-OH), 8.23-6.78 (m,13H,Ar-H), 5.64-5.60 (dd, 1H, C5 pyrazoline), 4.48 (s, 2H, -NH2), 3.69-3.63 (dd, 1H, C4cis pyrazoline), 3.19-3.14 (dd, 1H, C4trans pyrazoline); 13C NMR (DMSO) 100 MHz, δ ppm: 164.99 (C1 pyrimidine), 162.68 (C5 pyrimidine), 158.32 (C3 pyrimidine), 152.23 (C3 pyrazoline), 160.17-115.68 (18C, phenyl ring), 92.96 (C2 pyrimidine), 59.72 (C5 pyrazoline), 41.09 (C4 pyrazoline); Mass Spectra: MS: m/z 497 (M+).
4f: 1-[3/-(4//-methoxy phenyl)-5/-amino pyrimidine]-3-(4/-nitro phenyl)-5-(3/-nitro phenyl)-2-pyrazoline; IR (KBr, γmax, cm-1): 3521.02,3413.82 (NH2), 3089.80, 3042.72 (Ar-H), 2719.62, 2678.23 (C-H, asymmetric and symmetric stretching), 1662.82, 1596.12 (C=N), 1550.11 (C=C), 1542.11, 1372.12 (Ar-NO2), 1161.90 (C-N); 1H NMR (DMSO) 400 MHz, δ ppm: 8.22-6.85 (m, 13H, Ar-H), 5.62-5.58 (dd, 1H,C5 pyrazoline), 4.36 (s, 2H, -NH2), 3.71-3.65 (dd, 1H, C4cis pyrazoline), 3.80 (s, 3H, -OCH3), 3.20-3.15 (dd, 1H, C4trans pyrazoline); 13C NMR (DMSO) 100 MHz, δ ppm: 164.89 (C1 pyrimidine), 162.48 (C5 pyrimidine), 158.22 (C3 pyrimidine), 152.44 (C3 pyrazoline), 159.92-114.02 (18C, phenyl ring), 92.94 (C2 pyrimidine), 59.60 (C5 pyrazoline), 55.45 (1C, -OCH3), 41.23 (C4 pyrazoline); Mass Spectra: MS: m/z 511 (M+).
4g: 1-[3/-(3//-nitro phenyl)-5/-amino pyrimidine]-3-(4/-nitro phenyl)-5-(3/-nitro phenyl)-2-Pyrazoline; IR (KBr, γmax, cm-1): 3531.47, 3441.16 (NH2), 3079.99, 3049.19 (Ar-H), 1662.89, 1599.20 (C=N), 1559.23 (C=C), 1535.11, 1375.21 (Ar-NO2), 1160.82 (C-N); 1H NMR (DMSO) 400 MHz, δ ppm: 8.78-7.74 (m, 13H, Ar-H), 5.62-5.58 (dd, 1H, C5 pyrazoline), 4.41 (s, 2H, -NH2), 3.69-3.63 (dd, 1H, C4cis pyrazoline), 3.20-3.15 (dd, 1H, C4trans pyrazoline); 13C NMR (DMSO) 100 MHz, δ ppm: 164.90 (C1 pyrimidine), 162.70 (C5 pyrimidine), 158.42 (C3 pyrimidine), 152.62 (C3 pyrazoline), 148.97-121.44 (18C, phenyl ring), 93.67 (C2 pyrimidine), 59.66 (C5 pyrazoline), 41.34 (C4 pyrazoline); Mass Spectra: MS: m/z 526 (M+).
4h: 1- [3/- (2//,4//-dichloro phenyl)- 5/- amino pyrimidine]- 3- (4/- nitro phenyl)- 5- (4/- hydroxy phenyl)-2-pyrazoline; IR (KBr, γmax, cm-1): 3539.82, 3419.32 (NH2), 3315.61 (Ar-OH), 3088.20, 3058.19 (Ar-H), 1662.90,1598.21 (C=N), 1553.25 (C=C), 1538.18, 1379.20 (Ar-NO2), 1160.80 (C-N); 728.14 (C-Cl) 1H NMR (DMSO) 400 MHz, δ ppm: 9.3 (s, 1H, -OH), 8.20-6.68 (m, 12H, Ar-H), 5.61-5.57 (dd, 1H, C5 pyrazoline), 4.24 (s, 2H, -NH2), 3.66-3.60 (dd, 1H, C4cis pyrazoline), 3.19-3.14 (dd, 1H, C4trans pyrazoline); 13C NMR (DMSO) 100 MHz, δ ppm: 164.80 (C1 pyrimidine), 162.77 (C5 pyrimidine), 158.47 (C3 pyrimidine), 152.44 (C3 pyrazoline), 157.78-116.22 (18C, phenyl ring), 93.44 (C2 pyrimidine), 59.88 (C5 pyrazoline), 41.22 (C4 pyrazoline); Mass Spectra: MS: m/z 520 (M+).
Pharmacology:
Evaluation of Antimicrobial Activity: The in vitro antimicrobial studies were carried out by agar well diffusion method 35, 36. Preparation of nutrient broth, subculture and agar medium were done as per standard procedure. Each petri dish containing Muller-Hinton agar medium was inoculated with one bacterial culture by spreading the suspension of the organism with a sterile glass rod with a bended tip. For fungal culture potato-dextrose-agar (PDA) medium was used. In each plate wells of 10 mm diameter were made at equal distances using sterile cork borer. Each test compound (5 mg) was dissolved in dimethyl sulfoxide (5 ml) to give a concentration of 1000 μg/ml. All the compounds and standard were tested at (0.2 ml) 200 μg dose level and DMSO used as a control. One well was filled with 0.2 ml of standard drug and DMSO dissolved compounds were added into the other wells by using sterile pipettes simultaneously. The standard antibiotics ciprofloxacin for antibacterial activity and fluconazole for antifungal activity were also prepared at a concentration of 1000 μg/ml in sterilized distilled water and tested against the pathogen. The plates were incubated at 37 °C for 24 hour for bacteria and at 28 °C for 48 hour for fungi. After appropriate incubation the diameter of zone of inhibition of each well was measured. Duplicated were maintained and the average values were calculated for eventual anti-microbial activity.
RESULT AND DISCUSSION: The reaction sequence leading to the synthesis of targeted analogue 4(a-h) are outline in Scheme 1. These compounds were characterized by IR, 1H NMR, 13C NMR, mass spectra and elemental analysis. The physicochemical characterization data of synthesized compound 4(a-h) were given in Table 1. Elemental analysis showed that the percentage of nitrogen, hydrogen and carbon was found experimentally is equivalent to the calculated values in all compounds. The IR spectra showed 2 peaks in the region 3550–3400 cm-1 due to NH2 group and no C=O stretching. Ar-H vibrations are also observed in the region 3100-3030 cm-1. The peaks were found in the region 1664-1549 cm-1 due to C=N and C=C groups.
The 1H NMR (DMSO) spectra showed multi-plates in the range δ8.8-6.6 ppm due to aromatic protons. Singlet at δ4.4, δ3.8, δ3.04 ppm and δ9.6-δ8.5 ppm due to –NH2 of pyrimidine ring, -OCH3, –N(CH3)2, and –OH substituents at phenyl ring respectively. The 13C NMR (DMSO) spectra showed peaks in the range of δ41.10, δ59.60 and δ92.7 ppm for C4- pyrazoline, C5-pyrazoline and C5-pyrimidine respectively. IR peaks proved the presence of particular functional groups and mass spectra helps to find the molecular weight of the synthesized compounds. The molecular ion peaks were equivalent to the molecular weight of proposed compounds. Hence m/z value confirms the molecular weight of respective synthesized compound.
The synthesized pyrazoline derivatives 4(a-h) were evaluated for antimicrobial activity against bacterial and fungal strains by agar well diffusion method. The micro-organisms selected for antibacterial activity was Bacillus substilis, Streptococcus aureus: gram positive strain and Pseudomonas aeruginosa, Escherichia coli: gram negative strain. Aspergillus niger was selected for antifungal activity. All compounds emerged as active and showed moderate to high activity against both bacterial and fungal strains. 4h is highly active for all micro-organisms selected for study. All compounds were highly active for Pseudomonas aeruginosa and Streptococcus aureus. 4a, 4b, 4c, 4d, 4e, 4f, 4g are moderately active for Escherichia coli and Bacillus substilis. 4a, 4d and 4h showed high activity for Aspergillus niger whereas others are moderately active. Thus it can be observed that all compounds exhibited higher antibacterial activity as compared to antifungal activity Table 2. Comparison of diameter of zone of inhibition of 4(a-h) with standard “Ciprofloxacin” and “Fluconazole” are represented in Fig. 1.
SCHEME 1: SYNTHESIS OF 1-[3/-(SUBSTITUTED PHENYL)-5/-(AMINO PYRIMIDINE)]-3-(4/ NITRO PHENYL)-5-(SUBSTITUTED PHENYL)-2-PYRAZOLINES
CONCLUSION: All compounds were found to be sensitive against all selected microorganisms and showed moderate to high activity. 4h was found to be most effective against all selected microorganisms. The antibacterial activity was found to be better than antifungal activity.
ACKNOWLEDGEMENT: Authors is thankful to director SAIF / CIL, Punjab University Chandigarh for providing spectral and analytical data and the department of chemistry RCERT Chandrapur, Gondwana University Gadchiroli for providing laboratory facilities.
CONFLICT OF INTEREST: There is no conflict of interest.
REFERENCES:
- Desai NC, Rajpara KM and Joshi VV: Synthesis and characterization of some new quinoline based derivatives endowed with broad spectrum antimicrobial potency. Bioorganic and Medicinal Chemistry Letters 2012; 22: 6871-6875.
- Upadhyay S, Tripathi AC, Paliwal S and Saraf SK: 2-pyrazoline derivatives in neuropharmacology: Synthesis, ADME prediction, molecular docking and in vivo biological evaluation. EXCLI Journal 2017; 16: 628–649.
- Beyhan N, Kocyigit-Kaymakcioglu B, Gümrü S, Aricioglu F: Anticonvulsant of pyrazoline: Synthesis and anticonvulsant activity of some 2-pyrazolines derived from chalcones. Arabian Journal of Chemistry 2017; 10(2): S2073-S2081.
- Kumar V, Kaur K, Karelia DN, Beniwal V, Gupta GK, Sharma AK and Gupta AK: Synthesis and biological evaluation of some 2-(3,5-dimethyl-1H-pyrazol-1-yl)-1-arylethanones: antibacterial, DNA photocleavage and anticancer activities. Eur J Med Chem 2014; 81: 267-276.
- Havrylyuk D, Zimenkovsky B, Vasylenko O, Craig WD, Smee DF, Grellier P and Lesyk R: Synthesis and biological activity evaluation of 5-pyrazoline substituted 4-thiazolidinones. Eur J Med Chem 2013; 66: 228-237.
- Monteiro A, Gonçalves LM and Santos Maria MM: Synthesis of novel spiropyrazoline oxindoles and evaluation of cytotoxicity in cancer cell lines. Eur J Med Chem 2014; 79: 266-272.
- Kumar V, Kaur K, Karelia DN, Beniwal V, Gupta GK, Sharma AK and Gupta AK: Synthesis and biological evaluation of some 2-(3,5-dimethyl-1H-pyrazol-1-yl)-1-arylethanones: Antibacterial, DNA photocleavage and anticancer activity. Eur J Med Chem 2014; 81: 267-276.
- Jadhav SA, Kulkarni KM, Patil PB, Dhole VR and Patil SS: Design, synthesis and biological evaluation of some novel pyrazoline derivatives. Der Pharma Chemica 2016; 8(3): 38-45.
- Ahmad A, Husain A, Khan SA, Mujeeb M and Bhandari A: Synthesis, antimicrobial and antitubercular activities of some novel pyrazoline derivatives. Journal of Saudi Chemical Society 2016; 20(5): 577-584.
- Desai SS, Sastry VG, Malpani A and Singh K: Synthesis, characterization, antimicrobial and antitubercular activity of Some Pyrazoline derivatives from Chalcones bearing indane-1, 3-dione as nucleus. International Journal of Research and Development in Pharmacy and Life Science 2017; 6(2): 2530-2534.
- Mahdi MF, Raauf AMR and Mohammed NM: Synthesis, characterization and preliminary pharmacological evaluation of new non‐steroidal anti‐inflammatory pyrazoline derivatives. European Journal of Chemistry 2015; 6(4): 461‐
- Fernandes J, Revanasiddappa BC, Ishwarbhat K, Kumar MV, D’Souza L and Alva SS: Synthesis and in-vitro Anti-Inflammatory Activity of Novel Pyrazoline Derivatives. Research J. Pharm. and Tech. 2017; 10(6): 1679-1682.
- Mohammad A, Abdul RB, Fareeda A and Amir A: Synthesis, spectral studies and antiamoebic activity of new 1- N- substituted thiocarbamoyl-3 -phenyl- 2-pyrazolines. European Journal of Medicinal Chemistry 2009; 44: 417-425.
- Parveen H, Mukhtar S and Azam A: Novel Ferrocenyl Linked Pyrazoline Analogs as Potent Antiamoebic Agents. Journal of Heterocyclic Chemistry 2016; 53(2): 473–478.
- Marella A, Shaquiquzzaman M, Akhter M, Verma G, Alam MM: Novel pyrazole-pyrazoline hybrids endowed with thioamide as antimalarial agents: their synthesis and 3D-QSAR studies. J Enzyme Inhib Med Chem 2015; 30(4): 597-606.
- Marella A, Akhter M, Shaquiquzzaman M, Tanwar O, Verma G, Alam MM: Synthesis, 3D-QSAR and docking studies of pyrimidine nitrile-pyrazoline: a novel class of hybrid antimalarial agents. Medicinal Chemistry Research 2015; 24(3): 1018–1037
- Chaudhary J, Patel K and Patel CN: Synthesis and biological screening of some cinnoline derivatives. International Journal of Uiversal Pharmacy and Biosciences 2014; 3(3): 128-140.
- Bhat IK and Jainey PJ: Antimicrobial studies of some substituted pyrazoline derivatives derived from acetyl hydrazines. Asian J Pharm Clin Res 2014; 7(4): 237-239.
- Dipankar B, Panneerselvam P and Asish B: Synthesis, Characterization and Evaluation of Analgesic, Anti-Inflammatory, Ulcerogenic Potential of Some 2-Pyrazoline Derivatives. Der Pharma Chemica 2012; 4(4): 1679-1688.
- Monteiro A, Gonçalves LM and Maria MM: Synthesis of novel spiro pyrazoline oxindoles and evaluation of cyto toxicity in cancer cell lines. European Journal of Medicinal Chemistry 2014; 79: 266-272.
- George RF, Fouad MA and Gomaa IEO: Synthesis and cytotoxic activities of some pyrazoline derivatives bearing phenyl pyridazine core as new apoptosis inducers. European Journal of Medicinal Chemistry 2016; 112: 48-59.
- Kini S and Gandhi AM: Novel 2-pyrazoline derivatives as potential antibacterial and antifungal agents. Indian Journal of Pharmaceutical Science 2008; 70(1): 105–108.
- Koçyiğit-Kaymakçıoğlu B, Beyhan N, Tabanca N, Ali A, Wedge DE, Duke SO, Bernier UR and Khan IA: Discovery and structure activity relationships of 2-pyrazolines derived from chalcones from a pest management perspective. Medicinal Chemistry Research 2015; 24(10): 3632–3644.
- Awadallan FM, Gary AP, Gary BD, Keeton AB and Canzoneri JC: Synthesis of some di-hydro pyrimidine based compound bearing pyrazoline moiety and evaluation of their anti-proliferative activity-an article. European Journal of Medicinal Chemistry 2013; 70: 273-279.
- Mohamed MM, Khalil AK, Abbass EM and El-Naggar AM: Design, synthesis of new pyrimidine derivatives as anticancer and antimicrobial agents. Synthetic Communication 2017; 47(16): 1441-1457.
- Verma AK, Singh AK, Islam MM: Synthesis, Characterization and Evaluation of Pyridopyrimidine Carboxylate Derivatives as Potential Antimicrobial and Anticancer Agents. International Journal of Pharmacy and Pharmaceutical Sciences 2014; 6(6): 341-345.
- Cannito A, Perrissin M, Luu-Duc C, Huguet F, Gaultier C and Narcisse G: Synthèse et propriétés pharmacologiques de quelques thiéno[2, 3 -d]pyrimidin- 4- one 2-thiones. European Journal of Medicinal Chemistry 1990; 25: 635-639.
- Dudhe R, Sharma PK and Verma PK: Pyrimidine containing furanose derivative having antifungal, antioxidant, and anticancer activity. Organic and Medicinal Chemistry Letters 2014; 4(3): 1-18.
- Mohamed MS, Youns MM and Ahmed NM: Novel indolyl-pyrimidine derivatives: synthesis, antimicrobial, and antioxidant evaluations. Medicinal Chemistry Research 2014; 23(7): 3374-3388.
- Pertusati F, Serafini S, Albadry N, Snoeck R and Andrei G: Phosphonoamidate prodrugs of C5-substituted pyrimidine acyclic nucleosides for antiviral therapy. Antiviral Research 2017; 143: 262-268.
- El-Din El-Ansary AK, Taher AT, El-Hamed El-Rahmany AA and El Awdan S: Synthesis, anti-inflammatory, analgesic and antipyretic activities of novel pyrano[2,3-c]pyrazoles and related fused ring derivatives. Journal of American Science 2014; 10(10): 284-294.
- Bhat IK and Kumar A: Pyrimidines as potent cytotoxic and anti-inflammatory agents. Asian J Pharm Clin Res 2017; 10(6): 237-239.
- Patle SK, Kawathekar N, Zaveri M and Kamaria P: Synthesis and evaluation of 2,4,6-trisubstituted pyrimidine derivatives as novel antileishmanial agents. Med Chem Res 2013; 22: 1756–1761.
- Mathew B, Suresh J and Anbazhagan S: Development of novel (1-H) benzimidazole bearing pyrimidine-trione based MAO-A inhibitors: Synthesis, docking studies and antidepressant activity. Journal of Saudi Chemical Society 2016; 20(1): S132-S139.
- Raghavendra R and Neelagund S: Partial purification and bio chemical characterization of anti-microbial and analgesic novel bio active protein (substances) from silkworm (Bombyxmori) fical matter. International Journal of Biomedical and Pharmaceutical Sciences 2009; 3: 74-78.
- Samshuddin S, Narayana B, Kunhanna B and Sarojani: Antimicrobial, analgesic, DPPH scavenging activities and molecular docking study of some 1, 3, 5-tri aryl-2-pyrazolines. Medicinal Chemistry Research 2012; 21: 2012-2022.
How to cite this article:
Hatwar YA: 1-[3/-(substituted phenyl) -5/- (amino pyrimidine)]- 3- (4/-nitro phenyl) 5-(substituted phenyl)- 2-pyrazolines: synthesis, chracterisation and antimicrobial screening. Int J Pharm Sci Res 2018; 9(2): 642-49.doi: 10.13040/IJPSR.0975-8232.9(2).642-49.
All © 2013 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
Article Information
26
642-649
544
1093
English
IJPSR
Y. A. Hatwar
Department of Chemistry, Rajiv Gandhi College of Engineering, Research and Technology, Chandrapur, Gondwana University, Maharashtra, India.
yogi16h@gmail.com
27 May, 2017
19 September, 2017
21 October, 2017
10.13040/IJPSR.0975-8232.9(2).642-49
01 February, 2018