Journal of Pharmacy And Bioallied Sciences
Journal of Pharmacy And Bioallied Sciences Login  | Users Online: 772  Print this pageEmail this pageSmall font sizeDefault font sizeIncrease font size 
    Home | About us | Editorial board | Search | Ahead of print | Current Issue | Past Issues | Instructions | Online submission




 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 6  |  Issue : 4  |  Page : 253-259  

Antimicrobial screening and one-pot synthesis of 4-(substituted-anilinomethyl)-3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives


1 Department of Pharmaceutical Chemistry, Maharaja Surajmal Institute of Pharmacy, (Affiliated to GGSIP University), Janakpuri, New Delhi, India
2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India

Date of Submission09-Dec-2013
Date of Decision12-Mar-2014
Date of Acceptance25-Mar-2014
Date of Web Publication16-Oct-2014

Correspondence Address:
Dr. Sandhya Bawa
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0975-7406.142956

Rights and Permissions
   Abstract 

Aim: Synthesis of series of 4-(substituted-anilinomethyl-3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives (4a-4k) and their in vitro antifungal and antibacterial screening. Materials and Methods: A series of compounds (4a-4k) was synthesized through direct reductive amination of 3-(naphthalen-2-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde with various substituted aromatic amines using NaBH 4 in the presence of I 2 as reducing agent. The reaction was carried out in anhydrous methanol under neutral conditions at room temperature. The structures of synthesized compounds (4a-4k) were established on the basis of IR, 1 H and 13 C-NMR, and mass spectral data. Results: All 4-(substituted-anilinomethyl-3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives (4a-4k) were tested in vitro for antifungal and antibacterial activities against different fungal and bacterial strains. Most of the compounds exhibited considerable antifungal activity, but poor antibacterial activity against the test strains. Conclusion: In the series compound 4e, 4g, 4j, and 4k, showed excellent antifungal activity against the fungal strain Aspergillus niger (MTCC) 281 and Aspergillus flavus MTCC 277 (% inhibition in the range of 47.7-58.9).

Keywords: Antimicrobial activity, naphthalene, pyrazole, reductive amination


How to cite this article:
Goel N, Drabu S, Afzal O, Bawa S. Antimicrobial screening and one-pot synthesis of 4-(substituted-anilinomethyl)-3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives. J Pharm Bioall Sci 2014;6:253-9

How to cite this URL:
Goel N, Drabu S, Afzal O, Bawa S. Antimicrobial screening and one-pot synthesis of 4-(substituted-anilinomethyl)-3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives. J Pharm Bioall Sci [serial online] 2014 [cited 2020 Nov 27];6:253-9. Available from: https://www.jpbsonline.org/text.asp?2014/6/4/253/142956

Pyrazole and its derivatives constitutes an important class of heterocyclic compounds and has received widespread attention due to their diverse pharmacological activities such as anti-inflammatory - analgesic, [1],[2],[3] antimicrobial, [4],[5] anticancer, [6],[7] antihypertensive, [8],[9] antidiabetic, [10],[11] antidepressant-anticonvulsant, [12],[13] etc. There are numerous pyrazole containing drugs approved by United States Food and Drug Administration for appropriate therapeutic indications some of which includes celecoxib, lonazolac, crizotinib, etc. [Figure 1] presents some of the pyrazole derived therapeutic agents and represent the molecular varsity of pyrazole nucleus. However, some recent studies reported the potential of pyrazole derivatives as dual anti-inflammatory - antimicrobial agents. [14],[15] In view of all these facts and as the continuation of our work on the synthesis of pyrazole derivatives, [16],[17],[18] we undertook the one pot synthesis of naphthyl incorporated pyrazole compounds and their antimicrobial screening.
Figure 1: Chemical structures of various pyrazole containing drugs

Click here to view



   Materials and Methods Top


Melting points were determined by the open capillary method with electrical melting point apparatus and are uncorrected. IR spectra were recorded as KBr (pallet) on Nicolet, Protege 460 Fourier transform infrared spectroscopy (FTIR) spectrophotometer and 1 H and 13 C-NMR spectra recorded on Bruker DPX 300 MHz spectrophotometer using DMSO-d 6 or CDCl 3 as a NMR solvent. Tetramethylsilane was used as internal standard and chemical shift data reported in parts per million (in ppm) where s, broad singlet (bs), d, t, and m designated as singlet, bs, doublet, triplet, and multiplet, respectively. Mass spectra-electrospray ionization (MS-ESI) were recorded on a JEOL-AccuTOF JMS-T100LS mass spectrometer with a direct analysis in real time and elemental analysis on C, H, N Analyzer Perkin Elmer 2400. Thin layer chromatography (TLC) was performed to monitor progress of the reaction and purity of the compounds, spot being located under iodine vapor or ultraviolet-light. The synthesis of compounds was achieved as per scheme outlined in [Figure 2].
Figure 2: Route of synthesis for compounds (4a-4k) as Scheme 1. Reagent and conditions: (a) Phenyl hydrazine, abs. EtOH, reflux (b) DMF/POCl3, 55-60°C, warm (c) aromatic amines, NaBH4/I2, MeOH, stirring

Click here to view


Synthesis of 1-[1-(naphthalen-2-yl) ethylidene]- 2-phenylhydrazine (2)

A mixture of 2-acetylnaphthalene 1 (1.7 g or 0.01 mol) and phenyl hydrazine (0.012 mol) was refluxed in round bottom flask containing absolute ethanol (30 ml) for 2.0 h in presence of few drops of acetic acid. The content of the flask was cooled to give solid product which was filtered, washed with water, dried and recrystallized from ethanol as a yellow crystalline solid. The purity of compound was checked by TLC using (thin layer chromatography) (T:E:F, 5:4:1) as mobile phase.

Yield 89%; M.P. 165°C; IR (KBr)/cm: 3348 (NH), 1621 (C=N), 1588 (C=C). 1 H-NMR (300 MHz, DMSO-d 6 ): δ 2.35 (s, 3H, CH 3 ), 7.24-7.33 (m, 4H, Ar-H), 7.42-7.49 (m, 2H, Ar-H), 7.79-7.86 (m, 5H, Ar-H), 7.99 (s, 1H, Ar-H), 8.12-8.22 (d, 1H, Ar-H, J = 8.7 Hz), 10.7 (bs, 1H, NH). C, H, N analysis (C 18 H 16 N 2 , calculated/found %); C 83.04/83.39, H 6.19/6.15, N 10.76/10.82.

Synthesis of 3-(naphthalen-2-yl)-1-phenyl-1H-pyrazole-4- carbaldehyde (3)

To a cold solution of naphthyl hydrazones 2 (3.9 g or 0.015 mol) in DMF (25 ml) was added POCl 3 (5 ml, 39.5 mmol) and resulting mixture was stirred at 55-60°C for 5-6 h. Then the mixture was cooled to room temperature and poured in to ice-cold water. A saturated solution of sodium bicarbonate was added to neutralize the solution. The precipitate so formed was filtered, washed with water, dried and recrystallized from ethanol as a creamy-yellowish/yellowish white crystalline solid.

Yield 68%; M.P. 148°C; IR (KBr)/cm: 1676 (C = O), 1603 (C=N), 1591 (C=C). 1 H-NMR (300 MHz, DMSO-d 6 ): δ 7.38-7.43 (m, 1H, Ar-H), 7.51-7.56 (m, 4H, Ar-H), 7.82-7.85 (m, 3H, Ar-H), 7.89-7.97 (m, 4H, Ar-H), 8.33 (s, 1H, Ar-H), 10.18 (s, 1H, CHO). 13 C-NMR (DMSO-d 6 , 75 MHz) δ: 119.2, 121.8, 124.5, 125.2, 125.9, 127.1, 128.3, 128.8, 130.2, 131.8, 136.4, 137.9, 140.0, 157.9, 183.5 (CHO). MS (ESI): M/z 298 (M) + , 299 (M + 1), 270 (M-28). C, H, N analysis (C 20 H 14 N 2 O, calculated/found %); C 62.68/62.49, H 3.16/3.14, N 7.31/7.35.

General procedure for the synthesis of compounds (4a-4k)

To a solution of 3-(naphthalen-2-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde 3 (0.29 g, 1.0 mmol) in 10 ml of methanol, substituted aniline (1.2 mmol) was added and then 50 mg iodine (0.05 g, 0.4 mmol) was added with stirring at room temperature. To the stirred solution 55 mg of sodium borohydride (0.055 g, 1.4 mmol) was added slowly, stirring was continued for 3-6 h. The precipitate was formed which was filtered, washed with water, dried and recrystallized from ethanol/methanol to give crystalline product (4a-4k). The progress of reaction and purity of the compound was checked by (TLC), using benzene: acetone (9.5:0.5) as mobile phase.

4-(Anilinomethyl)-3-(2-naphthyl)-1-phenyl-1H-pyrazole (4a)

IR (KBr)/cm: 3402 (N-H), 1620 (C=N), 1595 (C=C), 1029 (C-N), 754 (C-Cl). 1 H-NMR (300 MHz, CDCl 3 ): δ 3.89 (s, 1H, NH, D 2 O-exchangeble), 4.49 (s, 2H, CH 2 ), 6.59-6.62 (d, 2H, Ar-H, J = 8.2 Hz), 6.89-7.01 (m, 3H, Ar-H), 7.27-7.35 (m, 2H, Ar-H), 7.48-7.54 (m, 3H, Ar-H), 7.79-8.01 (m, 5H, Ar-H), 8.06-8.10 (m, 2H, Ar-H), 8.31 (s, 1H, Ar-H). 13 C-NMR (CDCl 3 , 75 MHz) δ: 38.3 (CH 2 ), 114.8, 116.6, 119.2, 120.4, 121.5, 124.2, 125.8, 126.9, 127.1, 128.3, 128.9, 130.9, 137.9 , 138.6, 139.7, 143.8, 149.6. MS (ESI) m/z: 375 (M) + , 376 (M + 1). C, H, N analysis (%, calculated/found); C, 83.17/82.51, H 5.64/5.58, N 11.19/11.23.

4-(4-Chloroanilinomethyl)-3-(2-naphthyl)-1-phenyl-1H-pyrazole (4b)

IR (KBr)/cm: 3410 (N-H), 1625 (C=N), 1606 (C=C), 1032 (C-N). 1 H-NMR (300 MHz, CDCl 3 ): δ 3.82 (s, 1H, NH, D 2 O-exchangeble), 4.46 (bs, 2H, CH 2 ), 6.58-6.62 (d, 2H, Ar-H, J = 8.0 Hz), 7.13-7.17 (d, 2H, Ar-H, J = 7.8 Hz), 7.25-7.31 (m, 2H, Ar-H), 7.44-7.49 (m, 3H, Ar-H), 7.75-7.92 (m, 5H, Ar-H), 8.00-8.04 (m, 2H, Ar-H), 8.24 (s, 1H, Ar-H). C, H, N analysis (%, calculated/found); C 76.18/77.05, H 4.92/4.96, N 10.25/10.32.

3-(2-Naphthyl)-1-phenyl-4-(4-toluidinomethyl)-1H-pyrazole (4c)

IR (KBr)/cm: 3410 (N-H), 1619 (C=N), 1597 (C=C), 1028 (C-N). 1 H-NMR (300 MHz, CDCl 3 ): δ 2.26 (s, 3H, CH 3 ), 3.85 (s, 1H, NH, D 2 O-exchangeble), 4.45 (s, 2H, CH 2 ), 6.62-6.64 (d, 2H, Ar-H, J = 8.4 Hz), 7.01-7.04 (d, 2H, Ar-H, J = 7.8 Hz), 7.25-7.31 (m, 2H, Ar-H), 7.44-7.49 (m, 3H, Ar-H), 7.75-7.92 (m, 5H, Ar-H), 8.00-8.04 (m, 2H, Ar-H), 8.24 (s, 1H, Ar-H). 13 C-NMR (CDCl 3 , 75 MHz) δ: 20.7 (CH 3 ), 38.8 (CH 2 ), 114.7, 119.4, 120.1, 121.8, 125.2, 125.9, 127.5, 128.1, 128.7, 129.6, 130.5, 131.7, 137.4, 138.5, 140.3, 144.8, 149.8. MS (ESI) m/z: 389 (M) + . C, H, N analysis (%, calculated/found); C 83.26/83.68, H 5.95/6.01, N 10.79/10.86.

4-(4-Bromoanilinomethyl)-3-(2-naphthyl)-1-phenyl-1H-pyrazole (4d)

IR (KBr)/cm: 3420 (N-H), 1639 (C=N), 1590 (C=C), 1031 (C-N). 1 H-NMR (300 MHz, CDCl 3 ): δ 3.88 (s, 1H, NH, D 2 O-exchangeble), 4.50 (s, 2H, CH 2 ), 6.64-6.65 (d, 2H, Ar-H, J = 8.6 Hz), 7.12-7.15 (d, 2H, Ar-H, J = 8.0 Hz), 7.29-7.35 (m, 2H, Ar-H), 7.43-7.47 (m, 3H, Ar-H), 7.77-7.96 (m, 5H, Ar-H), 8.01-8.04 (m, 2H, Ar-H), 8.27 (s, 1H, Ar-H). C, H, N analysis (%, calculated/found); C 68.73/69.07, H 4.44/4.51, N 9.25/9.33.

4-(3-Chloroanilinomethyl)-3-(2-naphthyl)-1-phenyl-1H-pyrazole (4e)

IR (KBr) cm -1 : 3416 (N-H), 1629 (C=N), 1589 (C=C), 1047 (C-N). 1 H-NMR (300 MHz, CDCl 3 ): δ 3.88 (s, 1H, NH, D 2 O-exchangeble), 4.51 (s, 2H, CH 2 ), 6.60-6.64 (m, 2H, Ar-H), 6.94-6.97 (m, 1H, Ar-H), 7.05-7.08 (m, 1H, Ar-H), 7.21-7.26 (m, 2H, Ar-H), 7.42-7.53 (m, 3H, Ar-H), 7.80-7.98 (m, 5H, Ar-H), 8.04-8.09 (m, 2H, Ar-H), 8.30 (s, 1H, Ar-H). C, H, N analysis (%, calculated/found); C 76.18/76.65, H 4.92/4.97, N 10.25/10.30.

4-(4-Methoxyanilinomethyl)-3-(2-naphthyl)-1-phenyl-1H-pyrazole (4f)

IR (KBr)/cm -1 : 3389 (N-H), 1610 (C=N), 1593 (C=C), 1027 (C-N), 751 (C-Cl). 1 H-NMR (300 MHz, CDCl 3 ): δ 3.76 (s, 3H, OCH 3 ), 3.83 (s, 1H, NH, D 2 O-exchangeble), 4.40 (bs, 2H, CH 2 ), 6.59-6.62 (d, 2H, Ar-H, J = 8.4 Hz), 6.93-6.96 (d, 2H, Ar-H, J = 7.8 Hz), 7.27-7.33 (m, 2H, Ar-H), 7.45-7.53 (m, 4H, Ar-H), 7.79-7.95 (m, 4H, Ar-H), 8.02-8.07 (m, 2H, Ar-H), 8.28 (s, 1H, Ar-H). C, H, N analysis (%, calculated/found); C 79.97/78.28, H 5.72/5.75, N 10.36/10.42.

4-(4-Fluoroanilinomethyl)-3-(2-naphthyl)-1-phenyl-1H-pyrazole (4g)

IR (KBr)/cm: 3410 (N-H), 1635 (C=N), 1596 (C=C), 1034 (C-N), 728 (C-Cl). 1 H-NMR (300 MHz, CDCl 3 ): δ 3.86 (s, 1H, NH, D 2 O-exchangeble), 4.47 (s, 2H, CH 2 ), 6.63-6.66 (d, 2H, Ar-H, J = 8.4 Hz), 7.07-7.12 (m, 2H, Ar-H), 7.30-7.36 (m, 2H, Ar-H), 7.43-7.50 (m, 3H, Ar-H), 7.68-7.72 (m, 1H, Ar-H), 7.809-7.94 (m, 4H, Ar-H), 8.03-8.08 (m, 2H, Ar-H), 8.27 (s, 1H, Ar-H). C, H, N analysis (%, calculated/found); C 79.37/79.11, H 5.12/5.10, N 10.68/10.73.

3-(2-Naphthyl)-4-(4-nitroanilinomethyl)-1-phenyl-1H-pyrazole (4h)

IR (KBr)/cm: 3421 (N-H), 1632 (C=N), 1601 (C=C), 1039 (C-N), 765 (C-Cl). 1 H-NMR (300 MHz, CDCl 3 ): δ 3.84 (s, 1H, NH, D 2 O-exchangeble), 4.51 (s, 2H, CH 2 ), 6.60-6.63 (d, 2H, Ar-H, J = 8.4 Hz), 7.01-7.06 (m, 2H, Ar-H), 7.30-7.36 (m, 2H, Ar-H), 7.44-7.52 (m, 3H, Ar-H), 7.79-7.94 (m, 5H, Ar-H), 8.01-8.06 (m, 2H, Ar-H), 8.24 (s, 1H, Ar-H). C, H, N analysis (%, calculated/found); C 74.27/74.51, H 4.79/4.82, N 13.32/13.37.

3-(2-Naphthyl)-1-phenyl-4-(3-toluidinomethyl)-1H-pyrazole (4i)

IR (KBr)/cm: 3426 (N-H), 1612 (C=N), 1598 (C=C), 1039 (C-N). 1 H-NMR (300 MHz, CDCl 3 ): δ 2.25 (s, 3H, CH 3 ), 3.84 (s, 1H, NH, D 2 O-exchangeble), 4.51 (bs, 2H, CH 2 ), 6.58-6.61 (m, 2H, Ar-H), 6.89-6.93 (m, 1H, Ar-H), 7.01-7.04 (m, 1H, Ar-H), 7.25-7.29 (m, 2H, Ar-H), 7.42-7.54 (m, 3H, Ar-H), 7.78-7.96 (m, 5H, Ar-H), 8.01-8.05 (m, 2H, Ar-H), 8.27 (s, 1H, Ar-H). C, H, N analysis (%, calculated/found); C 83.26/83.04, H 5.95/5.94, N 10.79/10.83.

4-(3-Chloro-4-fluoroanilinomethyl)-3-(2-naphthyl)-1-phenyl-1H-pyrazole (4j)

IR (KBr)/cm: 3432 (N-H), 1636 (C=N), 1604 (C=C), 1035 (C-N). 1 H-NMR (300 MHz, CDCl 3 ): δ 3.85 (s, 1H, NH, D 2 O-exchangeble), 4.52 (s, 2H, CH 2 ), 6.63-6.66 (m, 2H, Ar-H), 6.89-6.93 (m, 1H, Ar-H), 7.01-7.04 (m, 1H, Ar-H), 7.25-7.29 (m, 2H, Ar-H), 7.42-7.54 (m, 3H, Ar-H), 7.78-7.96 (m, 4H, Ar-H), 8.01-8.05 (m, 2H, Ar-H), 8.27 (s, 1H, Ar-H). C, H, N Analysis (%, calculated/found); C 72.98/72.74, H 4.48/4.50, N 9.82/8.87.

4-(3,4-Dichloroanilinomethyl)-3-(2-naphthyl)- 1-phenyl-1H-pyrazole (4k)

IR (KBr)/cm: 3438 (N-H), 1620 (C=N), 1603 (C=C), 1033 (C-N). 1 H-NMR (300 MHz, CDCl 3 ): δ 3.89 (s, 1H, NH, D 2 O-exchangeble), 4.60 (s, 2H, CH 2 ), 6.62-6.65 (m, 2H, Ar-H), 6.90-6.93 (m, 1H, Ar-H), 7.03-7.07 (m, 1H, Ar-H), 7.25-7.31 (m, 2H, Ar-H), 7.41-7.46 (m, 2H, Ar-H), 7.80-7.97 (m, 5H, Ar-H), 8.02-8.06 (m, 2H, Ar-H), 8.24 (s, 1H, Ar-H). C, H, N analysis (%, calculated/found); C 70.28/70.14, H 4.31/4.28, N 9.46/9.50.

Antimicrobial activity

The newly synthesized compounds were screened for their antifungal and antibacterial activities against the test organism viz. Candida albicans Microbial Type Culture Collection (MTCC)-183, Aspergillus niger MTCC 281, Aspergillus flavus MTCC 277, Escherichia coli National Collection of Type Cultures (NCTC) 10418, Staphylococus aureus NCTC 6571, Pseudomonas aeruginosa NCTC 10662 in DMSO by cup plate method. [19],[20] Potato dextrose agar and nutrient agar were used as culture medium for antifungal and antibacterial activity respectively. Using an agar punch, wells were made on these seeded agar plates and dilution of 500 μg/ml of test compounds in DMSO was added into each well, labeled previously. A control was also prepared using solvent DMSO. The petri plate were prepared and maintained at 30° for 72 h for fungi and at 37°C for 24 h for bacteria. Each experiment was repeated twice and the average of the two independent determinations was recorded. Antimicrobial activity was determined by measuring zone of inhibition and results were reported as percentage inhibition and calculated as 100 (C − T)/C, where C is the average diameter of fungal or bacterial growth on the control plate and T is the average diameter of fungal or bacterial growth on test plate. Activity of each compound was compared with standard fluconazole (100 μg/ml) for antifungal and ciprofloxacin (100 μg/ml) for antibacterial activity. Results of antimicrobial activity have been summarized in [Table 1].
Table 1: Antifungal and antibacterial activity data of 4-(substituted-anilinomethyl)-3-(2-naphthyl)-1-phenyl-1H-pyrazole (4a– 4k)

Click here to view



   Results and Discussion Top


Chemistry

The various secondary amines (4a-4k) were synthesized by direct reductive amination using NaBH 4 in the presence of I 2 as reducing agent. [16] The reaction was carried out by simply stirring 1.0 equivalent of pyrazolyl carboxaldehyde 3 and 1.2 equivalents of aromatic amine in methanol in the presence of the NaBH 4 /I 2 reagent. The iodine catalyzed the in situ formation of an imine at room temperature that was ultimately reduced in situ to the secondary amine by NaBH 4 . The structures of all the newly synthesized compounds were elucidated on the basis of IR and 1 H-NMR data. In addition, 13 C-NMR and mass spectral data of some of the compounds was also carried out in support of these proposed structures. Elemental analysis of compounds was found to be satisfactory and within the range of ± 0.4%. In the FTIR spectra of all the compounds (4a-4k) the absorption bands were observed in the range of 1589-1606/cm corresponding to C=C. The NH stretching and C-N stretching vibrations of -CH 2 NH- were observed in range of 3389-3420/cm and 1027-1047/cm, respectively. The functional group transformation of -CHO of compound 3 into -CH 2 NH- in compounds 4a-4k was established on the basis of IR, 1 H, 13 C NMR, and mass spectral data. In FTIR, the characteristic carbonyl C=O stretching band, which was observed at 1676/cm in compound 3 disappeared in FTIR spectra of compounds (4a-4k). In the 1 H-NMR spectra of compound three aldehydic proton resonated as a singlet at δ value 10.18, which disappeared in spectra of compounds 4a-4k and a new signal was observed at high up field δ value 4.40-4.52 integrating for two protons. The signal due to the NH proton was observed at δ value 3.82-3.89. The methylene group of -CH 2 NH- appeared as a singlet and/or bs due to coupling effect of NH proton whereas the NH signal was observed as a bs. Furthermore, in the 13 C-NMR spectrum of the compound 3 the signal due to the carbonyl carbon was observed at δ value 183.5 ppm. No carbonyl carbon signal was found in the 13 C-NMR spectra of two prototype compounds 4a and 4c and a new signal due to methylene carbon of -CH 2 NH- appeared at δ value 38.3 and 38.8, respectively. The above spectral analysis suggested the successful reductive amination of pyrazole carbaldehyde three. The physicochemical data of compounds (4a-4k) is presented in [Table 2]. The fact was further supported by MS (ESI) spectra of selected compounds 4a and 4c. In 1 H-NMR, the protons of naphthalene and phenyl rings were observed in aromatic region as multiplets due to coupling and overlapping of signals. While a singlet integrating for one proton appeared at δ value 8.24-8.31 arising due to H-5 proton of the pyrazole nucleus. These data are in agreement with structures assigned to the compounds (4a-4k). The spectral detail of individual compound (4a-4k) has been given in experimental section.
Table 2: Physicochemical data of 4-(substituted-anilinomethyl)-3-(2-naphthyl)-1-phenyl-1H-pyrazole (4a-4k)

Click here to view


Antifungal activity

All the 1H-pyrazolyl amines derivatives (4a-4k) of Scheme 1 displayed variable growth inhibitory effects against the test organism at concentration of 500 μg/ml in DMSO as shown in [Table 1] and [Figure 3]. Among the series of compounds (4a-4k), compounds 4b, 4d, 4e, and 4g showed good antifungal activity against C. albicans. The growth inhibitory effect of compounds (4a-4k) was more prominent against the fungal strain A. niger MTCC 281 and A. flavus MTCC 277. In this series compound 4e, 4g, 4j, and 4k, showed excellent antifungal activity against the fungal strain A. niger MTCC 281 and A. flavus MTCC 277 (% inhibition in the range of 47.7-58.9). While, rest of the compounds such as 4a, 4c, 4d, 4f, and 4i, displayed moderate antifungal activity. Only one derivative 4h expressed weak antifungal activity.
Figure 3: Bar diagram showing antifungal activity of compounds (4a-4k) against fungal strain Candida albicans, Aspergillus niger and Aspergillus flavus

Click here to view


Antibacterial activity

All the 1H-pyrazolyl amine derivatives (4a-4k) of Scheme 1 were also evaluated for antibacterial activity against the strains E. coli NCTC 10418, S. aureus NCTC 6571, P. aeruginosa NCTC 10662 at concentration of 500 μg/ml in DMSO by cup plate method. Results of antibacterial study are presented in [Table 1] and careful examination of [Table 1] and [Figure 4] revealed that most of molecules of Scheme 1 (4a-4k ) exhibited moderate to weak antibacterial activity against the test organism E. coli NCTC 10418, S. aureus NCTC 6571 at the concentration of 500 μg/ml. Compounds were completely inactive against the strain P. aeruginosa NCTC 10662.
Figure 4: Bar diagram showing antibacterial activity of compounds (4a-4k) against bacterial strain Escherichia coli, Staphylococus aureus and Pseudomonas auroginosa

Click here to view



   Conclusion Top


In the present study, one-pot synthesis 4- (substituted- anilinomethyl-3-(2-naphthyl)-1-phenyl-1H-pyrazoles (4a-4k) using NaBH4/I 2 as reducing agent. The current process offers advantages such as good yield, simple procedure, use easily available reagents, etc., The antimicrobial screening of these compounds against a panel of bacterial and fungal strains showed that compounds were more active toward the fungal strains compared to the bacterial strains, In this series compound 4e, 4g, 4j, and 4k, showed excellent antifungal activity against the fungal strain A. niger MTCC 281 and A. flavus MTCC 277 (47.7-58.9% inhibition).


   Acknowledgments Top


The author (NG) expresses sincere thanks to Maharaja Surajmal Institute of Pharmacy, Janakpuri, New Delhi for providing necessary facilities. Thanks are due to CDRI, Lucknow, India and IIT for recording spectral data.

 
   References Top

1.
Sugiura S, Ohno S, Ohtani O, Izumi K, Kitamikado T, Asai H, et al. Synthesis and antiinflammatory and hypnotic activity of 5-alkoxy-3-(N-substituted carbamoyl)-1-phenylpyrazoles. J Med Chem 1977;20:80-5.  Back to cited text no. 1
    
2.
Penning TD, Talley JJ, Bertenshaw SR, Carter JS, Collins PW, Docter S, et al. Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: Identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benze nesulfonamide (SC-58635, celecoxib). J Med Chem 1997;40:1347-65.  Back to cited text no. 2
    
3.
Hengen O, Siemer H, Doppstadt A. A new compound with analgesic and antiphlogistic effects. Arzneimittelforschung 1958;8:421-3.  Back to cited text no. 3
    
4.
Tanitame A, Oyamada Y, Ofuji K, Fujimoto M, Iwai N, Hiyama Y, et al. Synthesis and antibacterial activity of a novel series of potent DNA gyrase inhibitors. Pyrazole derivatives. J Med Chem 2004;47:3693-6.  Back to cited text no. 4
    
5.
Gilbert AM, Failli A, Shumsky J, Yang Y, Severin A, Singh G, et al. Pyrazolidine-3,5-diones and 5-hydroxy-1H-pyrazol-3 (2H)-ones, inhibitors of UDP-N-acetylenolpyruvyl glucosamine reductase. J Med Chem 2006;49:6027-36.  Back to cited text no. 5
    
6.
Balbi A, Anzaldi M, Macciò C, Aiello C, Mazzei M, Gangemi R, et al. Synthesis and biological evaluation of novel pyrazole derivatives with anticancer activity. Eur J Med Chem 2011;46:5293-309.  Back to cited text no. 6
    
7.
Li X, Lu X, Xing M, Yang XH, Zhao TT, Gong HB, et al. Synthesis, biological evaluation, and molecular docking studies of N,1,3-triphenyl-1H-pyrazole-4-carboxamide derivatives as anticancer agents. Bioorg Med Chem Lett 2012;22:3589-93.  Back to cited text no. 7
    
8.
Bonesi M, Loizzo MR, Statti GA, Michel S, Tillequin F, Menichini F. The synthesis and angiotensin converting enzyme (ACE) inhibitory activity of chalcones and their pyrazole derivatives. Bioorg Med Chem Lett 2010;20:1990-3.  Back to cited text no. 8
    
9.
Monge A, Aldana I, Alvarez T, Losa MJ, Font M, Cenarruzabeiti E, et al. 1-Hydrazino-4-(3,5-dimethyl-1-pyrazolyl)-5H-pyridazino[4,5-b] indole. A new antihypertensive agent. Eur J Med Chem 1991;26:655-8.  Back to cited text no. 9
    
10.
Cottineau B, Toto P, Marot C, Pipaud A, Chenault J. Synthesis and hypoglycemic evaluation of substituted pyrazole-4-carboxylic acids. Bioorg Med Chem Lett 2002;12:2105-8.  Back to cited text no. 10
    
11.
Wu D, Jin F, Lu W, Zhu J, Li C, Wang W, et al. Synthesis, structure-activity relationship, and pharmacophore modeling studies of pyrazole-3-carbohydrazone derivatives as dipeptidyl peptidase IV inhibitors. Chem Biol Drug Des 2012;79:897-906.  Back to cited text no. 11
    
12.
Abdel-Aziz M, Abuo-Rahma Gel-D, Hassan AA. Synthesis of novel pyrazole derivatives and evaluation of their antidepressant and anticonvulsant activities. Eur J Med Chem 2009;44:3480-7.  Back to cited text no. 12
    
13.
Ruhoðlu O, Ozdemir Z, Caliþ U, Gümüþel B, Bilgin AA. Synthesis of and pharmacological studies on the antidepressant and anticonvulsant activities of some 1,3,5-trisubstituted pyrazolines. Arzneimittelforschung 2005;55:431-6.  Back to cited text no. 13
    
14.
Bekhit AA, Hymete A, El-Din A Bekhit A, Damtew A, Aboul-Enein HY. Pyrazoles as promising scaffold for the synthesis of anti-inflammatory and/or antimicrobial agent: A review. Mini Rev Med Chem 2010;10:1014-33.  Back to cited text no. 14
    
15.
Bekhit AA, Abdel-Aziem T. Design, synthesis and biological evaluation of some pyrazole derivatives as anti-inflammatory-antimicrobial agents. Bioorg Med Chem 2004;12:1935-45.  Back to cited text no. 15
    
16.
Bawa S, Ahmad F, Kumar S. One-pot synthesis of diphenyl pyrazolylmethylanilines via reductive amination using NaBH 4 /I 2 and their antimicrobial screening. Monatsh Chem 2011;142:637-42.  Back to cited text no. 16
    
17.
Bawa S, Kumar S, Drabu S, Panda BP, Kumar R. Synthesis and antimicrobial activity of 2-chloroquinoline incorporated pyrazoline derivatives. J Pharm Bioallied Sci 2009;01:32-6.  Back to cited text no. 17
    
18.
Bawa S, Kumar H. Synthesis of 6-fluoro- 2-[4-formyl-3-(substituted phenyl) pyrazol-1-yl] Benzothiazoles as potential antibacterial agents. Indian J Heterocyl Chem 2005;14:249.  Back to cited text no. 18
    
19.
Kumar S, Bawa S, Kaushik D, Panda BP. Synthesis and in-vitro antimicrobial activity of secondary and tertiary amines containing 2-chloro-6-methylquinoline moiety. Arch Pharm (Weinheim) 2011;344:474-80.  Back to cited text no. 19
    
20.
Barry AL. The Antimicrobial Susceptibility Test: Principle and Practice. Philadelphia: Illus Lea and Febiger; 1976. p. 180. Biol Abstr 1977;64:25183.  Back to cited text no. 20
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]


This article has been cited by
1 TSA-catalyzed regioselective synthesis of medicinally important 4-aryl-substituted dihydropyrimidine derivatives fused to pyrazole and triazole scaffolds via an efficient and green Domino reaction
Mahnaz Farahi,Bahador Karami,Zohreh Banaki,Fatemeh Rastgoo,Khalil Eskandari
Monatshefte für Chemie - Chemical Monthly. 2017;
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
    Materials and Me...
    Results and Disc...
   Conclusion
   Acknowledgments
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed2158    
    Printed30    
    Emailed2    
    PDF Downloaded128    
    Comments [Add]    
    Cited by others 1    

Recommend this journal