SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITIES OF SOME NEW SUBSTITUTED IMIDAZOLESHTML Full Text
SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITIES OF SOME NEW SUBSTITUTED IMIDAZOLES
- Rambabu 1 J. Subbarao,* 1 and P. Pavan Kumar 2
Department of Pharmaceutical Chemistry 1, Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Guntur, A.P., India.
Department of Pharmacology 2, Padmavathi College of Pharmacy, Dharmapuri, Tamilnadu, India.
ABSTRACT: In the present study, a new series of 2, 4, 5- trisubstituted imidazoles derivatives were synthesized taking different aldehydes as substitutions. The preliminary characterization of synthesized compounds identified by physical constants determination and TLC. The chemical structures were confirmed by means of IR, 1H-NMR and Mass spectral data. The synthesized compounds were screened for their anti-microbial and antifungal activity using standard methods. Both gram positive and gram negative organisms such as E.coli, B.subtilis, S.aureus, A. niger, C.albicans were used. The compounds screened for their antibacterial and antifungal activities A1, A2, A4 have shown promising antibacterial and antifungal activity against as compared to standard drugs Ciprofloxacin and Griseofulvin. The compounds were also screened for their antidepressant activities using forced swimming test in mice in which A1, A2 and A6 are found to be most significant while compounds A4 and A5 showed moderate activity as compared to standard drug Fluoxetin. The compound A4, 4-(4, 5-diphenyl-1H-imidazole-2-yl) phenol exhibited excellent activity.
antifungal and activity
INTRODUCTION: Imidazole is a planar 5-membered ring and is amphoteric. That is, it can function as both an acid and as a base. As an acid, the pKa of Imidazole is 14.5, making it less acidic than carboxylic acids, phenols, and imides, but slightly more acidic than alcohols. The acidic proton is located on N-1. As a base, the pKa of the conjugate acid (cited above as pKBH+ to avoid confusion between the two) is approximately 7, making imidazole approximately sixty times more basic than pyridine.
The basic site is N-3, protonation gives the imidazolium cation, which is symmetrical. The compound is classified as aromatic due to the presence of a sextet of π-electrons, consisting of a pair of electrons from the protonated nitrogen atom and one from each of the remaining four atoms of the ring. Different drugs containing these basic moieties with good pharmacological activity have been reported earlier. They undergo different types of chemical reactions and are found useful in synthesis of variety of heterocyclic compounds. Imidazole and their derivatives were used for the synthesis of various types of medicinal compounds having a good therapeutic value.
Literature survey reveals that, imidazole derivatives exhibited diverse pharmacological activities. Such as, antimicrobial activity,1-6 anti-HCV and anti tumor activity,7 antinociceptive activity, leishmanicidal activity,8 anticonvulsant activity,9 GABA uptake inhibitory activity,12 cytotoxic,13,14 anticancer activity,15 antiproliferative activity,16, 17 aromatase inhibitory activities,18 antitubercular,19 anti fungal agents 20 etc. Based on above observation it is worthwhile to synthesis newer compounds for their pharmacological activities. The aim of present study is to synthesize new potential 2, 4, 5-trisubstituted Imidazole derivatives (A1-6) and to evaluate possible pharmacological activities like antifungal, antibacterial and antidepressant activities.
MATERIALS AND METHODS:
Melting points were determined by open capillary tubes and were found uncorrected. IR were recorded on FT-IR spectrometer (BRUKER) using KBr disc method. 1HNMR spectra were recorded on NMR spectrometer (BRUKER AV-300MHz) in DMSO. The compounds were analysed for elemental analysis and their percentages were found to be very near that of the calculated values. Physical parameters data of compounds are recorded in Table 1 and spectral data recorded in Table 2.
TABLE 1: PHYSICAL PARAMETERS AND ELEMENTAL ANALYSIS OF COMPOUNDS
|Rf||Elemental analysis (calculated)|
TABLE 2: SPECTRAL ANALYSIS OF SYNTHESISED COMPOUNDS
|Compound||IR (KBr) n (cm-1)||1H NMR (DMSO) d in ppm|
|A1||3037.96 (Ar-CH, st), 2840.85 (-NH,st),
1586.97 (-C=N, st), 1202.18 (-C-N,st)
|6.8-8.2 (15 H of phenyl ),
4.0 (1H of -NH)
|A2||3267.46 (-OH st), 3058.08 (Ar-CH,st),
2729.81 (-NH,st), 1536.00 (-C=N,st),
|7.4-8.4 (14 H of phenyl ),
2.5 (1H of –NH),
1.5 (1H of -OH)
|A3||3427.95 (CH=CH, st), 3211.91( –NH, st),
3060.83( Ar-CH, st), 1585.41 (-C=N, st),
1239.12( –C-N, st),
|7.6-8.6 (15 H of phenyl ),
5.4-5.6 (2H of –CH=CH ),
2.5 (1H of –NH)
|A4||3267.77 ( –NH, st), 3027.82 (Ar-CH,st),
2804.81 (-CH3,st), 1600.32 (-C=N, st),
1258.00 ( –C-N, st), 1028.38 (-C-O-C-,st)
|7.6-8.6 (15 H of phenyl ),
5.4-5.6 (2H of –CH=CH ),
3.5-4.0 (3H of CH3), 2.5 (1H of –NH)
|A5||3037.96 ( –NH, st), 2988.92 (Ar-CH,st),
1586.97 (-C=N, st), 1202.18 ( –C-N, st),
|6.4-7.8 (13 H of phenyl ),
2.2 (1H of –NH),
|A6||3267.46 (-OH, st), 3058.08 (ArCH, st),
2729.81 (–NH, st), 1602.33( –C=N, st),
1296.18 (–C-N, st)
|7.1-7.9 (14 H of phenyl ),
2.5 (1H of –NH),
1.8 (1H of -OH)
Synthesis of 2, 4, 5-triphenyl-1H-imidazole [A1 to A6]
0.01 mole of Benzil was refluxed with 0.01 mole of an aromatic aldehyde in presence of 5 ml of glacial acetic acid and 0.01 moles of ammonium acetate for 4 hours. After which the resulting reaction mixture was cooled to room temperature. The reaction mixture was then poured in 15 ml of water and kept for refrigeration overnight. The resulting precipitate was collected, dried and recrystallized from hot ethanol. Scheme was illustrated in Figure1. Physical data were given in the Table 3.
FIG 1: SCHEME FOR THE SYNTHESIS OF COMPOUNDS
TABLE 3: PHYSICAL DATA OF COMPOUNDS
The compounds were tested in-vitro for their antibacterial activity against two microorganisms viz. Gram positive organisms: Staphylococcus aureus (ATCC 29737) and Bacillus subtilis (ATCC 6633), Gram negative organism: Escherichia coli (NCTC 10418) which are pathogenic in human beings using Cup-plate agar diffusion method using Nutrient agar.
The compounds were tested in-vitro for their antifungal activity against Aspergillus niger (NCIM 596) and Candida albicans (NCIM 3102) using Cup-plate agar diffusion method using Sabouraud-Dextrose agar.
All the compounds were screened for antidepressant activity also. Behavioural despair was proposed as a model to test for antidepressant activity by Porsolt et al. (1977, 1978). It was suggested that mice or rats forced to swim in a restricted space from which they cannot escape are induced to a characteristic behaviour of immobility. This behaviour reflects a state of despair which can be reduced by several agents which are therapeutically effective in human depression.
RESULTS AND DISCUSSION:
All the synthesised compounds were characterized and identified by using different physico-chemical parameters. Such as, TLC, melting point, elemental analysis, IR and1HNMR. From the literature survey it reveals that, the substituted imidazoles have been reported for number of pharmacological activities. The prepared compounds were screened for their anti-bacterial activity by using cup-plate agar diffusion method against various gram positive, gram negative and fungal stains. Some of the compounds show comparable activity with that of the standard (Ciprofloxacin and Griseofulvin).
The compounds screened for their antibacterial and antifungal activities A1, A2, A4 have shown promising antibacterial and antifungal activity against E.coli (NCTC 10418), B. subtilis (ATCC 6633), S. aureus (ATCC 29737), A.niger (NCIM 596) and C.albicans (NCIM 3102) as compared to standard drug Ciprofloxacin and Griseofulvin. The results were shown in Table 4 and Fig 2 and 3. The compounds were also screened for their antidepressant activity at 100 mg/kg dose level. However, the compounds A1, A2 and A6 are found to be most significant while compounds A4 and A5 showed moderate activity as compared to standard drug Fluoxetin. Results were recorded in Table 5 and the graphical representation given in Fig 4.
TABLE 4: ANTI-BACTERIAL AND ANTI-FUNGAL ACTIVITY OF SYNTHESIZED COMPOUNDS
|Zone of inhibition at 200µcg/ml(in.mm)|
-Not identified against organism
FIG 2: GRAPHICAL PRESENTATION OF ANTIBACTERIAL ACTIVITY
FIG 3: GRAPHICAL PRESENTATION OF ANTIFUNGAL ACTIVITY
TABLE 5: ANTIDEPRESSANT ACTIVITY OF THE SYNTHESIZED IMIDAZOLE DERIVATIVES
|Compound||Duration of immobility(s)||% change from control|
Compounds were tested at 100 mg kg-1 dose level, I.P.
FIG 4: GRAPHICAL PRESENTATION OF ANTIDEPRESSANT ACTIVITY
CONCLUSION: The present work is a bonafide and novel for the synthesis of derivatives 2,4,5-trisubstituted imidazoles. In this view, we have made extensive review on substituted imidazole derivatives for their medicinal values with the help of chemical abstracts, journals, internet surfing and text books. Compounds A1, A2, A4 have shown promising antibacterial and antifungal activity. The compounds A1, A2 and A6 have shown promising antidepressant activity also.
The proposed work has given out many active antibacterial, antifungal and antidepressant agents. Some of the compounds have showed moderate activities. These compounds with suitable modification can be explored better for their therapeutic activities in the future. The promising biological activities may consider these compounds as a lead for drug development and drug discovery in future. The toxicity studies of these compounds will be carried out in future to find the effective therapeutic index.
ACKNOWLEDGEMENT: Authors greatly acknowledge to Padmavathi College of Pharmacy, Dharmapuri, Tamilnadu, India., for allowing to carry out the pharmacological studies. We are also thankful to Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Guntur, A.P., India., for their constant support to this work.
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How to cite this article:
Rambabu R, Subbarao J, and Kumar PP: Synthesis, Characterization and Biological Activities of Some New Substituted Imidazoles. Int J Pharm Sci Res 2015; 6(4): 1761-65.doi: 10.13040/IJPSR.0975-8232.6(4).1761-65.
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.
R. Rambabu, J. Subbarao,* and P. Pavan Kumar
Department of Pharmaceutical Chemistry, Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Guntur, A.P., India
27 August, 2014
29 November, 2014
27 December, 2014
01 April, 2015