Synthesis and Antimicrobial Evaluation of Some new Coumarinyl Schiff Base Derivatives

 

Abhishek Kumar, Pankaj Kumar*, Jean Sandra Pinto, Bhashini, Akshata

Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences,

NITTE (Deemed to be University) , Paneer, Deralakatte-575018, Mangalore, Karnataka.

 

ABSTRACT:

A series of new substituted coumarinyl schiff base (AJS1-AJS6) have been synthesized by condensing substituted 3-acetyl coumarin and substituted aniline in alcohol medium. The intermediate 3-acetyl coumarin were synthesized by Knoevenagel reaction between substituted salicylaldehyde and ethylacetoacetate in presence of piperidine as catalyst. The structures of the final synthesized compounds were characterized by IR, mass and ¹H NMR spectra. The synthesized compounds were screened for their antibacterial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa by tube dilution method. Most of the compounds exhibited promising antibacterial activity compared to the standard drug ciprofloxacin.

 

 

 

INTRODUCTION:

Coumarin (2H-1-Benzopyran-2-one) derivatives belong to one of the most widespread classes of natural compounds. They have been found to exhibit antitumour¹, antioxidant², anti-inflammatory, antimicrobial³ and antidiabetic activities. The antibacterial activity of coumarin and other 45 coumarin derivatives have been tested against strains of Bacillus cereus MIP 96016, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, and Staphylococcus aureus ATCC 25923.The inhibitory effects of coumarins were affected by their substitution patterns. Coumarin has fungicidal properties as well. Compounds containing an azomethine group (-CH=N-) known as Schiff bases are formed by the condensation of a primary amine with a carbonyl compound. Schiff bases and their complexes are largely studied because they interested and important properties such as their ability to bind reversibly oxygen redox systems in biological systems and oxidation of DNA.

 

 

Many biological important schiff bases ligands have been reported which possess antimicrobial⁴, anticonvulsant, antioxidant⁵, anti-inflammatory and antitumor⁶ activity. Hence an attempt was made towards the incorporation of schiff base with coumarin moiety and to probe how this combination could influence the antimicrobial activity.

 

MATERIALS AND METHODS:

All the chemicals were of analytical grade: salicylaldehyde, 5-nitro salicylaldehyde, 5-chloro salicylaldehyde piperidine, substituted aniline, glacial acetic acid, ethanol and ethylacetoacetate.

 

Melting points were determined by open capillary method and are uncorrected. Purity of the intermediates and final compounds were monitored by thin layer chromatography (TLC) using silica gel G plates. The spots were visualized under UV light and by the exposure to iodine vapors. n-Hexane: Ethylacetate (7:3) was used as solvent for running the TLC of these compounds. All IR spectra were recorded in Alpha Bruker using ATR method. ¹H NMR spectra were recorded on Bruker spectrophotometer (400 MHz) in DMSO-d₆ solvent using tetra methyl silane (TMS) as an internal standard.. Mass spectra was recorded by LCMS method.

General Procedure:

Synthesis of substituted 3-acetyl coumarin⁷:

A mixture of salicylaldehyde (0.05 mol) and ethylacetoacetate was added to 250ml conical flask. It was then condensed by adding sufficient piperidine dropwise with stirring in ice cold condition. The reaction mixture was then kept overnight in refrigerator. The solid lumps were broken in cold ethanol. The resulting yellow colored solid mass was then filtered and washed with cold ethanol to remove the excess piperidine. It was then recrystallised from ethanol to give white needle shaped crystals.

Synthesis of substituted 3-[1-(phenylimino)ethyl]-2H-chromen-2-one⁸ (AJS1-AJS6):

A mixture of substituted 3-acetyl coumarin (0.01 mol) and substituted benzaldehyde (0.01 mol) in 20 ml ethanol was refluxed for 4-5 hours with continuous stirring in presence of few drops of glacial acetic acid as catalyst. The reaction mixture was monitored by TLC. It was then cooled and added to ice cold water. The precipitated solid was filtered and recrystallised from ethanol.

 

 

Figure 1: Reaction scheme for Schiff base derivatives

 

Spectral data

3-[1-(3-nitrophenylimino)ethyl]-2H-chromen-2-one (AJS1)

IR (cm^-1):1511 (Ar C=C str), 816 (Ar C-H bend), 3083 (Ar C-H str), 1339 (Ar-NO₂ str), 1718 (C=O str), 1599 (C=N str).

¹H NMR (400 MHz, DMSO-d₆): δ 7.42-7.97 (m, 9H, Ar-H), 8.67 (s, 1H, -CH=N-).

Mass (m/z): 282 (M⁺)

 

3-[1-(3,4,5-trimethoxyphenylimino)ethyl]-2H-chromen-2-one (AJS2)

IR (cm^-1):1504 (Ar C=C str), 830 (Ar C-H bend), 3032 (Ar C-H str), 1223 (C-O str), 1698 (C=O str), 1611 (C=N str).

¹H NMR (400 MHz, DMSO-d₆): δ 7.41-7.97 (m, 7H, Ar-H), 8.68 (s, 1H, -CH=N-), 3.35 (s, 9H, OCH₃).

Mass (m/z): 340 (M⁺)

 

Antimicrobial Activity:

All the synthesized compounds were evaluated for their minimum inhibitory concentration by tube dilution method⁹. The synthesized test compounds were tested at different concentrations and ciprofloxacin was used as standard. Serial dilutions of the test compound was made in a liquid medium which was inoculated with a standardized number of organisms and incubated for 24 hrs. The lowest concentration of test compound preventing appearance of turbidity is considered to be the minimal inhibitory concentration (MIC). After preparation of different concentrations of the antimicrobial agent in brain heart infusion broth (by using the broth dilution method), we inoculate them with the tested organism. Then after incubation we can determine the MIC by choosing the lowest concentration in which no growth occurs.

 

RESULTS AND DISCUSSION:

Table 1: Physicochemical data of Schiff base derivatives (AJS1-AJS6)

Comp. code	R	Mol. formula	Mol. wt	M.P oC	Rf Value	% Yield
AJS1	H	C15H10N2O4	282	250-252	0.60	72
AJS2	H	C19H18NO5	340	236-238	0.72	68
AJS3	H	C18H15NO2	277	210-212	0.52	70
AJS4	H	C17H13NO3	279	272-274	0.68	75
AJS5	6-NO2	C17H11N3O6	353	268-270	0.74	60
AJS6	6-Cl	C18H14ClNO2	311	222-224	0.58	62

 

Table 2: Antimicrobial activity of the compounds (AJS1-AJS6) by tube dilution method

Comp. code	Minimum inhibitory concentration (μg/ml)
	S.aureus	B.subtilis	E.coli	P.aureginosa
AJS1	12.5	12.5	1.6	25
AJS2	1.6	1.6	R	R
AJS3	R	R	1.6	1.6
AJS4	50	50	25	50
AJS5	3.1	6.3	6.3	12.5
AJS6	100	50	50	100
Ciprofloxacin	1	2	2	1

 

Antimicrobial activity:

The in vitro antibacterial of the synthesized compounds were determined by using tube dilution⁹ method. The results of antibacterial activity of newly synthesized compounds are reported against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa respectively. Compounds AJS2, AJS3 and AJS5 showed significant antibacterial activity compared to the standard drug ciprofloxacin. The presence of electron releasing groups like methoxy, methyl and electron withdrawing group like nitro resulted in increased antibacterial activity. The results are shown in Table 2.

 

CONCLUSION:

The study reports the successful synthesis of coumarin incorporated schiff base derivatives with moderate yields and most of the synthesized compounds showed good antibacterial activity.

 

ACKNOWLEDGEMENTS:

The authors are thankful to NITTE (Deemed to be University) for providing the necessary facilities to carry out this research. The authors are grateful to Sequent Research Ltd, Mangalore and Central Instrumentation Facility, MIT Manipal for providing spectral data.

 

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Accepted on 12.07.2018           © RJPT All right reserved

Research J. Pharm. and Tech 2018; 11(11): 4946-4948.