DOI: http://dx.doi.org/10.26510/2394-0859.pbe.2017.34

Research Article

Synthesis, characterization and biological evaluation of Schiff's bases derivatives as potent antibacterial agents

Versha Parcha1*, Ankit Kumar1, Babita Mahajan2, Jaswinder Kaur3

Department of Chemistry, 1Sardar Bhagwan Singh PG Institute of Biomedical Sciences and Research, Balawala, Dehradun, Uttarakhand, 2GGM Science Colleges, Jammu, India 3Department of Applied Sciences, IIMT College of Engineering Noida Uttar Pradesh, India

*For correspondence

Dr. Versha Parcha,

Department of Chemistry, Sardar Bhagwan Singh PG Institute of Biomedical Sciences and Research, Balawala, Dehradun, Uttarakhand, India.

Email: vershaparcha@ gmail.com

 

 

Received: 31 July 2017

Revised: 29 August 2017

Accepted: 31 August 2017

ABSTRACT

Objective: To design, synthesize and screen biologically newer Substituted Schiff bases by condensing substituted acid hydrazides with various benzaldehydes and explore their antimicrobial potential.

Methods: Present study synthesis of various derivatives of Schiffs bases was carried out by: firstly converting substituted acids to acid hydrazides and then to Schiff's bases after condensation with substituted benzaldehyde. Synthesized compounds were characterised on the basis of spectral studies (like UV, IR, and NMR). All the synthesized derivatives were screened further for their antibacterial effect against Salmonella typhimurium, Shigella sonnei, Staphylococcus aureus& Bacillus cereus.

Results: From this study it could be observed that schiff's bases 2-[( aminophenylhydrazinyldene o,m,dinitrobenzoyl] aniline (H) and compound 2-[( aminophenylzinyldene) p amino benzoyl] aniline (I) showed very good zone of inhibition against almost all strains tested for.

Conclusions: So further attempts could be made to extend the series and explore their antibacterial potential to achieve hopeful goal.

Keywords: Antimicrobial, Schiff's base, Shigella sonnei

Introduction

Antimicrobials are defined as the chemical substances or agents obtained from natural or derived from synthetic origin employed to treat various infections caused by various types of microorganism. The antimicrobial agents are broadly categorized as respectively in antibiotics and antibacterial. Over, the past few decades, intensive and haphazard use of antibiotics has lead to drug resistant microbial pathogens necessitating the need for research for new antimicrobial agents with reduce resistant to pathogens and for better biological activity.

Schiff's bases have exhibited versatile biological activities like anthelmintic and anti-intestinal nematode, antioxidant, antibacterial, anti-inflammatory, anticonvulsant, antioxidant, antimycobacterial etc.1-8 The most commonly prescribed class of antibacterial in 2006 was reported to be the Schiff's bases derivatives.8-13 However, increased indiscriminate prescribing has led to the recent occasional emergence of Schiff's base derivatives resistant bacteria which has necessitated the search for newer drugs with efficacy against such resistant strains and hence continued efforts are being taken to get potent, nontoxic, broad spectrum antibacterial agents. Encouraged by different findings of these reports and to cope up with the current requirements of developing newer, safer and broad spectrum antibacterial agents the present work was undertaken as a part of world wide effort to design, synthesize and screen biologically newer Schiff's bases derivatives by condensing substituted acid hydrazides with various substituted benzaldehydes and explore their animicrobial potential.14

Materials and Methods

The chemicals used in the present project work were of A.R Grade and L.R Grade, purchased from Himedia, Rankem, and CDH labs. Melting point of the synthesized compounds were taken in the capillary tubes and Thiel's tubes melting point apparatus. Purity of the compound was checked by thin layer chromatography using silica gel G as stationary phase and various combinations of solvents as mobile phase mixture of petroleum ether and ethyl acetate in 1:1 ratio. The spot resolved were visualized by using iodine chamber. The compounds are synthesized by conventional method. The technique employed for the characterization of the synthesized compound was I.R Spectra and ¹HNMR Spectra. The IR spectra of synthesized compound were recorded on a Fourier Transform IR spectrometer (model Shimadzu 8400s) in the range of 400-4000 using KBR Pallets and the value of νmax is written in cm.1

Figure 1: Schematic representation of synthesis of Schiff's bases derivatives.

S.No R1 R2
A -P-NH2 -H
B -P-NO2 -P-NO2
C O,P,-NO2NO2 -P-NO2
D O-NH2 -P-NO2
E -H -P-NO2
F m-NH2 H
G m-NO2 -P-NH2
H O,m-dinitro -P-NH2
I -P-NH2 -P-NH2
J -P-NO2 -P-NH2
K O,P,-NO2NO2 -P-NH2

General procedure for synthesis of compounds

The general procedure for synthesis of compounds takes place in following steps:

(a) Synthesis of methyl ester (ii) from substituted acid (i)

2 gms of substituted acid, 20 ml of methanol and few drops of HCL were placed in a 250 ml round bottom flask (RBF) and refluxed the mixture under anhydrous condition for 6 hours. The reaction was monitored by TLC, using chloroform. On completion of reaction mixture excess of alcohol was distilled off on water bath and allowed to cool. Product was collected and recrystallised.

(1) R1COOH +CH3OH    dil.hcl R1 COOCH3

(b) Synthesis of acid hydrazide (iii) from methyl ester (ii)

2 ml of ester 50 ml of methanol and 1.5 ml of hydrazine hydrate were placed in a 250 ml of round bottomed flask and refluxed the mixture for 7 hours under anhydrous condition. The reaction was monitored by TLC using various ratios of chloroform, petroleum ether and ethyl acetate. Spots were observed in iodine vapours. After completion of reaction, excess amount of alcohol was distilled off on a water bath.

(2) R1 COOCH3+NH2NH2 ===> R 1CONHNH2

(c) Synthesis of hydrazone (iv) from acid hydrazide (iii)

To solution of acid hydrazide 2.68 ml was added 1.75 gm of anhydrous sodium acetate in 30 ml of water and 1.67 ml benzaldehyde and mixture was well shaken till hydrazone formed. The solid was collected by suction filtration and wash it with little aqueous methanol.

(3) R 1CONHNH2 + C6H5C=O ===>R1CONHN=C.C6H5

(d) Synthesis of 2-[(Substitutedphenylhy-drazinyldene) Substituted benzoyl] aniline (IV – A-K)

To solution of substituted 4-aminobenzohydrazide 1mole was added 1.75 gm of anhydrous sodium acetate in 30 ml of water and 1 mole of substituted benzaldehyde and mixture was well shaken till sustituted derivatives of [(phenylhydrazinyldene) benzoyl] anilines were formed. The solids so obtained were collected by suction filtration and wash it with little aqueous methanol.

Antibacterial activity

Under modern system of medicine bacterial infection are generally treated by antibiotics. Present study reported the anti-bacterial activity of substituted Schiff's base derivatives compounds against certain microbial pathogens viz., E. coli, Klebsiella pneumoniae, Salmonella, Shigella. These cultures were maintained on nutrient agar slant at first being incubated at 37°C for about 18-24 hours and then stored at 4ºC. Fresh cultures obtained by transferring a loopful of culture into Muller Hinton Broth and then incubated at 37°C overnight. To test anti-microbial activity, disc diffusion method was used.

(a) Preparation of culture media

The medium for anti-bacterial activity was nutrient agar that was prepared and sterilized at 121°C and 15 lbs for 15-30 mins.

(b) Plate preparation and determination of inhibitory potentials of test samples

20-25 ml of autoclaved Muller Hinton agar medium was poured into 90 mm diameter pre-sterlized petriplates under aseptic conditions and was allowed to solidify at room temperature.

(c) Assay

Disc diffusion method

For the preparation of disc whatman filter paper No-42 were used to prepare discs (dia. 6 mm) are sterilized with (50 mg/ml) stock solvent of respective solvent extract. The petriplates were incubated at 37°C for 24 hours. The inhibition zone diameters were observed and recorded after 24-36 hours in case of bacteria by measuring the zone (diameter) after suitable incubation in mm.

Results and Discussion

Schiff's bases are reported to have broad-spectrum anti-microbial, antifungal, ant tubercular, anticancer and anti-HIV of the clinicians. A number of these compounds hold antibacterial market in terms of global revenue, increasingly being used in both the hospital and community sectors to treat broad range of infections due to their therapeutic efficacy having tolerable side effects. In view of this present study synthesis of Schiff's base was carried out by firstly converting substituted acids to acid hydrazides and then to Schiff's bases after condensation with substituted benzaldehyde. Synthesized compounds were characterised on the basis of spectra study showing UV λmax 255-280 nm, IR KBr νcm-1 at 3300, 3391.30, 1603, 3356 and H1 NMR exhibited signals at δ 8.00 - 7.00 for aromatic protons and conspicuous doublet at δ 6.85 for olefenic proton and for NH protons between δ 2.59 - 3.19 showing highly substituted aromatic ring and formation of schiff's bases.

Table 1: Characterization of compounds.

Compound UV (λmax) nm IR KBR (√cm-1) H1 NMR(δ)
A 257 3300 (NH) 3391 (NH) 3102 (C-H) 1603 (C=C) 8.20-7.53ArH 6.83d1H N=CH 2.96 (brs2H,NH2)
B 258 3396 (NH) 2856 (C-H) 1689 (CoNH) 1518 (C=C) 8.04-7.55 (m,ArH) 6.85 (N=CH) 3.29 (NH)
C 263 3485 (NH2) 3226 (C-H) 1671 (CONH) 1429 (C=C) 8.0-7.38 (m,ArH) 6.83 (d1H N=CH) 3.05 (brs NH)
D 259 3395 (NH2) 1707 (CONH) 2952 (C-H) 1602 (C=C) 7.56-6.68 (m,ArH) 6.58 (d1H N=CH) 2.62 (brs,NH2)
E 257 3300 (NH) 3391 (NH) 3102 (C-H) 1603 (C=C) 8.0-7.38 (m,ArH) 6.83 (d1H N=CH) 3.05 (brs NH)
F 264 3250 (NH) 3387 (NH) 3100 (C-H) 1650 (C=C) 8.0-7.23 (m,ArH) 6.86(d1H N=CH) 3.05 (brs NH)
G 258 3300 (NH) 3389 (NH) 3100(C-H) 1657 (C=C) 8.10-7.36 (m,ArH) 6.69 (d1H N=CH) 3 (brs NH)
H 262 3200(NH) 3400(NH) 3107 (C-H) 1603 (C=C) 7.89-7.38 (m,ArH) 6.82 (d1H N=CH) 3.10 (brs NH)
I 261 3300 (NH) 3391 (NH) 3102 (C-H) 1667(C=C) 7.97-7.28 (m,ArH) 6.78 (d1H N=CH) 2.99 (brs NH)
J 259 3280 (NH) 3397 (NH) 3099(C-H) 1605 (C=C) 7,97-7.41 (m,ArH) 6.59 (d1H N=CH) 2.98(brs NH)
K 257 3286 (NH) 3391 (NH) 3092 (C-H) 1656(C=C) 8.0-7.38 (m,ArH) 6.83 (d1H N=CH) 3.05 (brs NH)

Table 2: Antimicrobial activity of synthesized compounds.

S. No. Microorganisms Zone of inhibition (mm) Chloroam-phemicol
    A B C D E F G H I J K  
1. S. typhimurium 16 22 18.3 14 15 18 21 29 27 17 19 23
2. Shigella Sonnei 14.6 19.5 24.6 8 11 15 16 31 23 15 21 21
3. S. aureus 17 20.3 13.6 14 23 14 19 26 25 15 19 24
4. Bacillus cereus 11.6 23.7 10 18 21 12 16 28 29 17 18 26

The synthesized compounds were screened further for their antibacterial effect against Salmonella typhimurium, Shigella sonnei, Staphylococcus aureus and Bacillus cereus. From this study it could be observed that all the compounds exhibited very good antibacterial potential specifically compound 2-[( aminophenylhydrazinyldene o,m,dinitrobenzoyl] aniline (H) and compound 2-[( aminophenylzinyldene) p amino benzoyl] aniline (I) showed very good zone of inhibition against all the strains Salmonella typhhimurium, Shigella sonnei, Staphylococcus aureus and Bacillus cereus showing zone of inhibition of 29, 31, 26, 28, 27, 23, 25, 29 mm respectively while other compounds in the series showed moderate effect against all these strains. Structure activity relationship studies revealed that substitution by nitro and amino gp in Schiff's base moiety resulted in the enhancement of activity. So further attempts could be made to extend the series with incorporation of nitro and amino moiety& explore their antibacterial potential to achieve hopeful goals.

Conclusion

From the series it can be concluded that compound (H) & (I) showed maximum zone of inhibition against all the strains tested for. So further attempts could be made to extend the series and explore their antibacterial potential to achieve hopeful goal.

Acknowledgements

The authors gratefully acknowledge to Director and Management of SBSPGI, Balawala, Dehradun, India for providing the necessary facilities during this experimental study.

Funding: No funding sources

Conflict of interest: None declared

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