SYNTHESIS OF NOVEL SCHIFF’S BASES AND THEIR BIOLOGICAL ACTIVITIES
HTML Full TextSYNTHESIS OF NOVEL SCHIFF’S BASES AND THEIR BIOLOGICAL ACTIVITIES
Arvind Singh Shekhawat, Narendrapal Singh Chauhan, Girdharpal Singh and Narendra Singh Chundawat *
Department of Chemistry, Faculty of Science, Bhupal Nobles’ University, Udaipur, Rajasthan, India.
ABSTRACT: A new series of Schiff's base compounds were synthesized by condensation of 1-(4-amino-4 phenyl) 3-phenyl triazene-1-ol) and substituted aldehyde and gave high yields of target compounds. Antimicrobial activity of compounds has been tested against bacterial and fungal species, namely gram-positive bacteria as S. aureus and S. pyogenes, gram-negative bacteria as E. coli and P. aeruginosa, and fungal species C. albicans and A. clavatus are selected based on their clinical and pharmacological importance. Bacterial and fungal tests were performed under the same conditions using Cefixime and Griseofulvin as standard drugs. It has been found that synthesized Schiff's base has shown efficient antibacterial and anti-fungal activities. Thus they can be revealed as potent antimicrobial compounds. They are widely used for industrial purposes and also exhibit a broad range of biological activities. The structures of synthesized compounds were confirmed by TLC, melting point, Infrared spectroscopy, and proton nuclear magnetic resonance spectroscopy (1HNMR) data.
Keywords: Schiff’s base, Aldehyde, Antibacterial, Anti-fungal
INTRODUCTION: Schiff’s bases, named after Hugo Schiff, are formed when, under specific conditions, any primary amine interacts with an aldehyde or a ketone 1. Structurally a Schiff’s base is an aldehyde or ketone nitrogen analogue in which the imine or the azomethane group has been substituted for the carbonyl group, and it has an ability to modulate the activities of many enzymes involved in metabolism. The pharmacophore potential of this group is due to its ability to form complex compounds with bivalent and trivalent metals found at the active core of various enzymes involved in metabolic reactions. Azomethane pharmacophore is used in the production of new bioactive molecules 2.
Schiff’s base has attracted a lot of attention due to its broad range of promising applications such as antibacterial activity 3, anti-fungal 4, anticancer 5, antidepressant 6, antioxidant, and analgesic 7. Matar and coworkers have reported the synthesis of 3, 3-diaminodipropylamine, and different derivatives of benzaldehyde having excellent bactericidal and fungicidal properties 8. Teran and coworkers have reported a series of new Schiff’s base from 4-aminoantipyrine with excellent antibacterial, anti-fungal, leishmanicidal, and antioxidant activities for clinical applications 9. The goal of the present research is to develop novel Schiff’s bases for potential applications as antimicrobial agents. Herein, we report the preparation of Schiff’s base derived from 1-(4-amino-4 phenyl) 3-phenyl triazene-1-ol), Aldehyde with reasonably good antibacterial and antifungal activities.
EXPERIMENTAL SECTION:
Material and Methods: IR spectra of the structures were recorded in KBr pellets with a Shimadzu FT-IR spectrophotometer in the 4000-400 cm-1 range. The 1HNMR spectra were measured at JEOL II 400 MHz from Delhi University, New Delhi. Melting points were examined in open capillary tubes.
All the chemicals used were of analytical reagent grade (AR) and of maximum purity available. All reagents were commercially available. Solvents were purified and dried according to the standard procedures.
General Procedure: A solution of 1-(4-amino-4 phenyl) 3-phenyl triazene-1-ol (0.1mole was dissolved in ethanol) and was added slowly to a solution of aldehyde 1a-1e (0.1 mole was dissolved in 50 ml ethanol). Stirrer the reaction mixture for 2-3 hr maintaining the reflux temperature at 75-80 °C. Cool the reaction mixture, allow to form precipitates. Filter the mass, washed with ice-cold water, recrystallizes from ethanol to afford 8-9 g 2a-2e reddish-brown shining crystals 10-13.
The molecular structure of Schiff’s base is given in Fig. 1.
FIG. 1: STRUCTURE OF SCHIFF’S BESE (2A-2E)
RESULTS AND DISCUSSION: Typically, the structure of Schiff's base compounds were obtained under reflux of 1-(4-amino-4 phenyl) 3-phenyl triazene-1-ol suitable with aromatic aldehyde 1a-1e at a 1: 1 mole ratio. The purity of the Schiff's base 2a-2e and the obtained structures were tested by TLC, melting point, FT-IR, and 1H NMR. The proposed molecule's structure is represented in Fig. 1. 2a–2e Schiff's base compounds are novel and have not yet been reported till date in the literature.
TABLE 1: SCHIFF’S BASE STRUCTURE, MELTING POINT, MOLECULAR WEIGHT AND YIELD
FT-IR Analysis: FT-IR spectroscopy provides information on molecular vibration or precision in transitions between vibrational and rotational energy levels in molecules. Absorption bands detected in the region of 1580-1450 cm-1 confirm the presence of (>C=N-) Schiff’s base moiety respectively, where the bandwidth around 3750-3480 cm-1 confirms the presence of hydrogen-bonded ν(O-H) stretching vibration. The FTIR data obtained for both Schiff bases are tabulated in Table 2. It is observed in the range 3500-3750 cm-1 which shows the presence of O-H stretching frequency (Represented in Table 2) 14-15.
TABLE 2: FTIR OF SCHIFF’S BASES
Schiff’s base | ν(O-H) | ν (N=N) | ν(C=N) |
2a | 3734 | 1456 | 1541 |
2b | 3550 | 1444 | 1555 |
2c | 3652 | 1510 | 1468 |
2d | 3525 | 1458 | 1495 |
2e | 3710 | 1474 | 1520 |
1H NMR analysis: 1H NMR spectra of the Schiff’s base structure were recorded in chloroform Table 3. The multiplet, which extends from δ 7.0 to δ 7.6 is equal to 13 protons present in aromatic rings. A singlet at δ 7.8-8.2 ppm is attributed to the presence of CH=N- linkage. The signal at δ 3.96 ppm corresponds to –CH3 proton (3H). The 1H NMR spectra of Schiff's base provide additional support for the confirmation of the proposed structure of Schiff's base. In the 1HNMR spectra of Schiff’s base, Schiff’s base showed a signal, ν (O-H) at 8.8-9.9 ppm.
TABLE 3: SELECTED1HNMR OF SCHIFF’S BASES
Schiff’s Base | -N=CH- | Aromatic | -OH | -CH3 |
2a | 7.8-7.9 | 7.41-7.42 (M) | 8.90-(S,1H) | 3.96
(S,3 H) |
2b | 7.9-8.0 | 7.40-7.6(M) | 9.80(S,1H) | - |
2e | 7.8-8.0 | 7.30-7.5(M) | 9.80(S,1H) | - |
Antimicrobial Activity of Schiff’s Base:
Anti-bacterial and Anti-fungal Activity: 16 Bacteria strains Gram-positive bacteria as S. aureus and S. pyogenes, Gram-negative bacteria as E. coli and P. aeruginosa, and Fungal strains C. albicans and A. clavatus are selected based on their clinical and pharmacological importance. Bacterial microbes were prepared in agar / YEPD genetics using a plate-spreading process, and fungal stock culture is placed 24 hours at 37 °C in a potato dextrose agar (PDA) medium (Micro care laboratory, Surat, India), following refrigeration on 4 °C. Bacterial species were grown on Mueller-Hinton agar (MHA) plates at 37 °C (bacteria were planted in nutrient broth at 37 °C and stored in agar slants at 4°C), while yeast and fungi were planted in Sabouraud dextrose agar(SDA) and in the PDA media, respectively, at 28°C. Standard cultures were maintained at 4 °C.
Determination of Zone of Inhibition Method: 17 In-vitro anti-bacterial and antifungal activities were tested on a sample. Activities of a sample against two Grams (+), two Grams (-), and two fungi have been investigated by the distribution of the agar disk diffusion method. Each sample was diluted with dimethyl sulfoxides, sterilized by filtration using a sintered glass filter, and stored at 4 °C. By determining the prevention area, Gram-positive, Gram-negative, and fungal species were treated as standard antibiotics. All compounds were tested for their antibacterial and antifungal activities against Gram-positive S. aureus, S. pyogenic and Gram-negative E. coli, P. aeruginosa and fungal strains A. clavatus and C. albicans. Dilution (25 μg / ml) of the sample and standard drugs (5, 25, and 50 μg / ml) were prepared in double-distilled water using nutritious agar tubes. Mueller-Hinton's sterile agar plates were infected with bacterial infections (108 cfu) and allowed to remain at 37 °C for three hours.
Control tests were performed under the same conditions using Cefixime and Griseofulvin as standard drugs. The zones of growth inhibition around the discs were rated after 18 to 24 h of incubation at 37 °C in bacteria and 48 to 96 h for fungus at 28 °C (including disk width) on the surface of the agar around the discs, and values <8 mm were considered as not active. Antibacterial and antifungal activities of both Schiff bases are tabulated in Tables 4 to 7.
Agar Diffusion Test (Mueller-Hinton Test): 18 It is a test that uses antibiotic -impregnate wafers to test whether certain bacteria are susceptible to certain antibiotics. A known number of bacteria are planted on agar plates in the presence of small wafers with appropriate antibiotics. When bacteria are attacked by certain antibiotics, the cleaning area around the wafer where bacteria cannot grow is called the zone of inhibition.
TABLE 4: ANTI-BACTERIAL ACTIVITY OF STANDARD ANTI-BACTERIAL DRUG
Standard Drug | Concentration
(µg/ml) |
MIC in mm | |||
S. pyogenes | S. aureus | E. coli | P. aeruginosa | ||
Cefixime | 5 µg/ml | 22 | 19 | 18 | 20 |
25 µg/ml | 29 | 26 | 25 | 28 | |
50 µg/ml | 33 | 35 | 36 | 37 |
TABLE 5: ANTI-FUNGAL ACTIVITY OF STANDARD ANTI-FUNGAL DRUG
Standard Drug | Concentration
(µg/ml) |
MIC in mm | |
C. albicans | A. clavatus | ||
Griseofulvin | 5 µg/ml | 34 | 35 |
25 µg/ml | 46 | 44 | |
50 µg/ml | 53 | 55 |
TABLE 6: ANTI-BACTERIAL ACTIVITY OF SCHIFF’S BASE
Group | Concentration
(µg/ml) |
MIC in mm | |||
S. aureus | S. pyogenic | E. coli | P. aeruginosa | ||
2a | 25 µg/ml | 18 | 13 | 22 | 14 |
2b | 25 µg/ml | 16 | 18 | 18 | 13 |
2c | 25 µg/ml | 15 | 22 | 17 | 18 |
2d | 25 µg/ml | 20 | 27 | 18 | 16 |
2e | 25 µg/ml | 17 | 25 | 18 | 19 |
TABLE 7: ANTI-FUNGAL ACTIVITY OF SCHIFF’S BASES
Group | Concentration
(µg/ml) |
MIC in mm | |
C. albicans | A. clavatus | ||
2a | 25 µg/ml | 20 | 21 |
2b | 25 µg/ml | 22 | 23 |
2c | 25 µg/ml | 20 | 21 |
2d | 25 µg/ml | 21 | 20 |
2e | 25 µg/ml | 22 | 19 |
CONCLUSION: Based on the results of this study, it can be concluded that a combination of 1-(4-amino-4 phenyl) 3-phenyl triazene-1-ol and aldehyde with a simple condensation process has been successfully achieved with a good mixing time of 2 to 3 hours. Both newly prepared Schiff base have shown reasonably good antibacterial and antifungal activities against various pathogenic bacteria and fungi.
ACKNOWLEDGEMENT: Authors are thankful to Delhi University and Jiwaji University, Gwalior, for FTIR, NMR analyses.
CONFLICTS OF INTEREST: The authors declare that there are no conflicts of interest regarding the publication of this article.
REFERENCES:
- Irawan C, Nur L, Mellisani B and Hanafi: Synthesis and characterization of Citral and Methylanthranilate Schiff’s base. Rasayan J.Chem 2019; 12(2): 951-58.
- Teran R, Guevara R and Mora J: Characterization of antimicrobial and antioxidant activities of Schiff’s base. Molecules 2019; 24(15): 2696.
- Anush SM, Vishalakashi B, Kalluraya B and Manju N: Synthesis of pyrazole –based Schiff’ base. Int J Biol Macromol 2018; 119: 446.
- Singh G, Singh J, Singh A, Kumar M, Gupta K and Chhibber S: synthesis and characterization of Schiff’s base. Journal of Organometallic Chemistry 2018; 21: 871.
- Saedi Z, Hoveizi E, Roushani M, Massahi S, Haidan M and Salehi K: Synthesis and characterization of Citral and Methylanthranilate Schiff’ base and their activities. J Mol. Struct 2018; 1176: 207.
- Buldurun TK: Synthesis, characterization and antioxidant activity of Schiff base and its metal complexes with Fe(II), Mn(II), Zn(II), and Ru(II) ions: catalytic activity of ruthenium(II) complex Eur J Chem.2018; 9: 22-29.
- Kaur P, Singh R, Kaur V and Talwar D: Anthranilic acid Schiff’s base as fluorescent probe for the detection of arsenate and selenite. Sensors and Actuators B 2018; 254: 533.
- Soufeena PP and Aravindakshan KK and Lumin J: Antipyrine derived Schiff base a colorimetric sensor for Fe (III) and turn on fluorescent sensor for Al (III) 2018.
- Liu X, Manzur C, Novoa N, Celedón S, Carrillo D and HamonJ.R: Multidentate unsymmetrically substituted Schiff bases and their metal complexes: Synthesis, functional materials properties, and applications to catalysis. Coord. Chem. Rev 2018; 357: 144-72
- Ashok NP, Yadav MU, Desai PA and Singare PU: Synthesis of some Novel Halogenated Platinum (II) Complexes of Active Schiff’s Base Ligand Derived from 5-Bromo Isatin and Evaluation of their Antibacterial Activity, World Scientific News 2015; 10: 32-43.
- Thomas AB, Nanda RK, Kothapalli LP and Hamane SC: Synthesis and characterization of Schiff’s base. Arab J Chem 2016; 9: 579.
- Karrouchi K, Chemlal L, Taoufik J, Cherrah Y, Radi S, Faouzi MEA and M Ansar: Characterization of antimicrobial activities of Schiff’s base derivatives of 4-Aminoantipyrine. Ann. Pharm. Fr 2016; 74(6): 431-35.
- Matar SA and Talib WH: Synthesis, Characterization and antimicrobial activity of Schiff’s base derived from Benzaldehyde and amines. Arab J Chem 2015; 8(6): 850-57.
- Chundawat NS, Pandya M, Singh GP and Chauhan RS: Antibacterial activity of hydroxy triazene, Schiff’s base and their ternary complexes. World Journal of Pharmacy and Pharmaceutical Science 2015; 4 (2): 330-35.
- Chundawat NS, Pandya M and Dangi RR: Synthesis Characterization of Schiff’s bases .International Journal of Pharmacy and Pharma Sci Research 2014; 6(3): 2859-63.
- Alzoreky NS and Nakahara K: Antibacterial activity of extracts from some edible plants commonly consumed in Asia. Int J Food Microbiol 2003; 223: 30.
- Rios JL Recio MC and Villar A: Screening methods for natural products with antimicrobial activity: A review of the literature. J Ethnopharmacol 1988; 127: 49.
- McCracken WA and Cowsan RA: New York: Hemispher Publishing Corporation; Clinical and Oral Microbiology 1983; 512.
How to cite this article:
Shekhawat AS, Chauhan NS, Singh G and Chundawat NS: Synthesis of novel schiff’s bases and their biological activities. Int J Pharm Sci & Res 2022; 13(1): 192-96. doi: 10.13040/IJPSR.0975-8232.13(1).192-96.
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Arvind Singh Shekhawat, Narendrapal Singh Chauhan, Girdharpal Singh and Narendra Singh Chundawat *
Department of Chemistry, Faculty of Science, Bhupal Nobles’ University, Udaipur, Rajasthan, India.
chundawat7@yahoo.co.in
14 February 2021
13 May 2021
01 June 2021
10.13040/IJPSR.0975-8232.13(1).192-96
01 January 2022