DESIGN AND PHARMACOLOGICAL EVALUATION OF NEW SCHIFF BASES AS POTENTIAL THERAPEUTIC AGENTS
- Dr. Garima Verma , Professor, Faculty of Pharmacy, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, India, Pin Code- 250005
- Dr. Pawan Singh , Associate Professor, Pharmacy Academy, IFTM University, Moradabad, Uttar Pradesh, India, Pin Code- 244001
- Dr. Hemendra Gautam , Professor and Dean, Future Institute of Pharmacy, Future University, Bareilly, Uttar Pradesh, India, Pin Code- 243503
- Dr. Jatin Jaiswal , Professor, Faculty of Pharmacy, Future Institute of Medical Sciences, Future University, Bareilly, Uttar Pradesh, India, Pin Code-243503
- Dr. Pragyandip Parthasarathi , Associate Professor, Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Science, Faculty of Pharmacy, Parul University, Vadodara, Gujrat, India, Pin Code- 391760
- Dr. Satnam Singh , Professor, AIMSR, Adesh University, Barnala Road, Bathinda, Punjab, India, Pin Code- 151101
- Ms. Purnima Rai , Principal, City School of Pharmacy, Lakshbar Bajha, Barabanki, Uttar Pradesh, India, Pin Code- 225412
- Dr. Pankaj Mishra , Principal and Professor, Rohilkhand College of Pharmacy, Bareilly International University, Rohilkhand Medical College Campus, Pilibhit Bypass Road, Bareilly, Uttar Pradesh, India, Pin Code- 243006.
- Ms. Rachana Belwal , Assistant Professor, Department of Pharmaceutical Chemistry, School of Pharmacy and Research, Dev Bhoomi Uttarakhand University, Dehradun, Uttarakhand, India, Pin Code-248007
Article Information:
Abstract:
A series of novel Schiff bases (NSB-1 to NSB-4) were synthesized and evaluated for their antimicrobial activity. The structures of the synthesized compounds were confirmed by melting point determination, thin-layer chromatography (TLC), infrared (IR) spectroscopy, and 1H-NMR spectral analysis. The antimicrobial activity of the title compounds was assessed against Bacillus subtilis (Gram-positive), Escherichia coli (Gram-negative), and Candida albicans. Ampicillin and clotrimazole were used as standard reference drugs for comparison. Among the tested compounds, NSB-4 exhibited the highest antimicrobial activity, showing a maximum zone of inhibition of 20 mm against B. subtilis. The results suggest that these Schiff base derivatives possess promising antimicrobial potential.
Keywords:
Article :
INTRODUCTION:
Schiff bases are compounds containing an imine or azomethine (–C=N–) functional group. They are typically formed by the condensation reaction of primary amines with carbonyl compounds and were first reported by Hugo Schiff. Infectious diseases continue to pose a major global health challenge, particularly in developing and underdeveloped countries. In addition, the increasing ability of microorganisms to develop resistance to existing antibiotics has intensified the need for the discovery and development of novel antimicrobial agents. The imine functional group present in Schiff bases has been shown to play a crucial role in a wide range of biological activities, with antibacterial and antifungal properties being especially prominent. In light of these observations and the growing threat of antimicrobial resistance, the present study focuses on the synthesis and antimicrobial evaluation of some new Schiff base derivatives.
EXPERIMENTAL
The melting points of the synthesized compounds were determined by the open capillary method and are uncorrected. The infrared (IR) spectra of the synthesized compounds were recorded in potassium bromide (KBr) discs using a Perkin Elmer RX1 spectrophotometer. The progress of the reactions was monitored by thin-layer chromatography (TLC) using silica gel G, and the spots were visualized under iodine vapor. All the target compounds were subjected to biological evaluation for antimicrobial activity.
Synthesis of Schiff Bases
Step I. Synthesis of 2-(4-chlorophenoxy)-1-phenylethanone(3) C14H11ClO2
Procedure
Equimolar amounts of 2-bromo-1-phenylethanone 1 (0.01mol), 4-chloro phenol 2 (0.01 mol) and anhydrous K2CO3 (0.02 mol) in dry acetonitrile was refluxed for about 6 h. The mixture was filtered and solvent was removed under reduced pressure. The resulting solid was washed with excess of water. The crude product was purified by recrystallization from ethanol to afford compound 3. (Molecular Formula - C14H11ClO2)
IR Spectra value of 2-(4-chlorophenoxy)-1-phenylethanone (3)
|
S.No. |
ν (cm-1) |
Functional Group |
|
1. |
3082 |
CH Str. Aromatic |
|
2. |
2917 |
CH Str. Aliphatic |
|
3. |
1701 |
C=O str. |
|
4. |
1595 |
C=C str. in aromatic |
|
5. |
1089 |
C-O str. in C-O-C |
Step II. Synthesis of target compounds: Schiff Bases (NSB-1 to NSB-4)
|
Schiff bases (NSB-1 to NSB-4) |
Synthesis of the target compounds.
Reagents and conditions: (i) Ethanol, Glacial Acetic Acid, Reflux.
Amino compounds used the preparation of Schiff bases-
|
Cpd. Code |
Amino compounds |
|
NSB-1 |
Aniline |
|
NSB-2 |
3-nitro aniline |
|
NSB-3 |
4-nitro aniline |
|
NSB-4 |
2-choloro-3-nitro aniline |
General procedure
A mixture of compound 3 (0.01 mol), amino compound 4 (0.01mol) and 1 ml of glacial acetic acid in ethanol was refluxed on water bath for 10 h. The mixture was allowed to cool, and then the separated solid was filtered and recrystallized from ethanol to afford the NSB-1 to NSB-4.
The physical parameters were of the target compounds (NSB-1 to NSB-4) were following:
N-(2-(4-chlorophenoxy)-1-phenylethylidene)benzenamine (NSB-1) - C20H16ClNO
N-(2-(4-chlorophenoxy)-1-phenylethylidene) benzenamine
|
S.No. |
ν (cm-1) |
Functional Group Assignment |
|
1. |
3065 |
CH Str. Aromatic |
|
2. |
2901 |
CH Str. Aliphatic |
|
3. |
1433 |
C=N str. |
|
4. |
1095 |
C-O str. in C-O-C |
IR Spectra value of N-(2-(4-chlorophenoxy)-1-phenylethylidene) benzenamine (NSB-1).
N-(2-(4-chlorophenoxy)-1-phenylethylidene)-3-nitrobenzenamine (NSB-2)- C20H15ClN2O3
|
S.No. |
ν (cm-1) |
Functional Group |
|
1. |
3062 |
CH Str. Aromatic |
|
2. |
2901 |
CH Str. Aliphatic |
|
3. |
1175 |
C-N str. |
|
4. |
1430 |
C=N str. |
|
5. |
1093 |
C-O str. in C-O-C |
IR Spectra value of (N-(2-(4-chlorophenoxy)-1-phenylethylidene)-3-nitrobenzenamine (NSB-2) N-(2-(4-chlorophenoxy)-1-phenylethylidene)-4-nitrobenzenamine (NSB-3)- C20H15ClN2O3
|
S.No. |
ν (cm-1) |
Functional Group |
|
1. |
3062 |
CH Str. Aromatic |
|
2. |
2906 |
CH Str. Aliphatic |
|
3. |
1175 |
C-N str. |
|
4. |
1432 |
C=N str. |
|
5. |
1092 |
C-O str. in C-O-C |
IR Spectra value of N-(2-(4-chlorophenoxy)-1-phenylethylidene)-4-nitrobenzenamine (NSB-3)
N-(2-(4-chlorophenoxy)-1-phenylethylidene)-2-chloro-3-nitrobenzenamine (NSB-4) -C20H14Cl2N2O3
|
S.No. |
ν (cm-1) |
Functional Group |
|
1. |
3069 |
CH Str. Aromatic |
|
2. |
2907 |
CH Str. Aliphatic |
|
3. |
1433 |
C=N str |
|
4. |
1178 |
C-N str. |
|
5. |
1089 |
C-O str. in C-O-C |
IR Spectra value of N-(2-(4-chlorophenoxy)-1-phenylethylidene)-2-chloro-4-nitrobenzenamine (NSB-4)
DETERMINATION OF ANTIMICROBIAL ACTIVITY:
The antimicrobial testing was performed using the cup diffusion technique. The synthesized compounds, as 1 mg/ml solutions in dimethylformamide (DMF), were evaluated in vitro for activity against C. albicans by the cup diffusion technique. Compounds showing inhibitory zones of at least 20 mm were considered active. Ampicillin and Clotrimazole were used as standard antimicrobial agents. Dimethylformamide was used as a control. Sterile nutrient agar was inoculated with the test organisms (each 100 mL of the medium received 1 mL of 24 h broth culture), and then seeded agar was poured into sterile petri dishes. Cups (8 mm in diameter) were cut in the agar, and each cup received 0.1 mL of the test compound solution. The plates were then incubated at 37oC for 24 h. The activities were estimated as zones of inhibition in mm diameter. Ampicillin and Clotrimazole solutions (0.01%) were used as reference standards. DMF did not show any inhibition zones.
The Antimicrobial Activity of Schiff bases (NSB-1 to NSB-4)
|
Cpd.Code |
Zone of Inhibition (in mm) against B. Subtilis |
Zone of Inhibition (in mm) against E. Coli |
Zone of Inhibition (in mm) against C. Albicans |
|
NSB-1 |
17 |
17 |
17 |
|
NSB-2 |
15 |
15 |
19 |
|
NSB-3 |
16 |
17 |
19 |
|
NSB-4 |
20 |
19 |
17 |
|
Ampicillin |
27 |
25 |
- |
|
Clotrimazole |
- |
- |
25 |
The compounds having zone of inhibition 20 or greater 20 mm is considered as active.
RESULTS AND DISCUSSION:
The results of the Schiff bases containing atoms chloro at 2 position and nitro at 3 position was showing most potent antibacterial activity against B. Subtilis as compared to the other Schiff bases but none of Schiff base was active against E.Coli and C.Albicans bacteria. Among the compound NSB-4 was showed most potent antifungal activity (20mm) against B. Subtilis in the test compounds.
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