Synthesis and Antimicrobial Evaluation of Different Substituted Phenylpropenone Pyrrolyl Chalcones

 

Pankaj Kumar, Abhishek Kumar*, Deeksha S, Nireeksha G, Shalet D’Souza

Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences, Nitte University, Paneer, Deralakatte-575018, Mangalore, Karnataka.

 

ABSTRACT:

The appearance to antimicrobial resistance to the antimicrobial agent has become a matter of high concern for health care professionals since last ten years. It will an effort to establish new phenylpropenone pyrrolyl; chalcones as improved antimicrobial agent. In this particular series of novel substituted phenylpropenone pyrrol (AP1-AP5) were synthesized by simple condensation reaction between different substituted aldehydes and 3 acetyl -2,4-dimethyl pyrrole in presence of a strong ethanolic base to yield the chalcones. 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 aeruginosaby cup plate method. Most of the compounds exhibited promising antibacterial activity

 

 

 

 

 

INTRODUCTION:

Phenypropenones belong to chalchone family, have displayed an impressive array of biological activities, among which anti-malarial[1], anti-cancer[2,3], anti-tuberculosis[4], cardiovascular, antileishmanial[5], anti-mitotic[6], anti-hyperglycemic[7], nitric oxide inhibition anti-inflammatory[8], tyrosinase inhibition, activities have been reported. Chalcones are also key precursors in the synthesis of many biologically important heterocycles such as benzothiazepine, pyrazolines, 1, 4-diketones , and flavones. Thus the synthesis of chalcones has generated vast interest to organic as well as for medicinal chemist. The presence of a reactive α-β unsaturated keto function in chalcones is found to be responsible for their antimicrobial activity.

 

which may be altered depending on the type and position of substituent on the aromatic rings. In view of these observations it was thought to synthesize some new series of chalcone derivatives.

 

MATERIALS AND METHODS:

All the chemicals were of analytical grade: 3 Acetyl -2,4-dimethyl pyrrole and , substituted benzaldehyde, urea and potassium hydroxide. Melting points were determined by open capillary method and are uncorrected. The purity of the compounds was 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. The homogeneity of the compounds was checked on silica gel-G coated plate by using Ethylacetate: n-hexane as solvent. 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 were recorded by LCMS method.

 

General Procedure:

The synthesis consists of the two major steps which are as follows: To a mixture of ethyl 3-Acetyl-2,4-dimethyl pyrrole (0.01 mol) and the substituded aldehyde (0.01 mol) in oxygen-free ethanol was added to a solution of 40% sodium hydroxide in distilled water with constant stirring of the reaction flask. The reaction mixture was stirred for 24 hours on a magnetic stirrer and poured on to crushed ice. The solid mass that separated out was filtered, washed with water and crystallized from ethanol to furnish the desired product chalcones.

 

SCHEME:

 

R= H, Cl, F, CH₃, OCH₃

 

1-(3,5-Dimethyl-1H-pyrrol-2-yl)-3-phenylprop-2-en-1-oneAP1

IR (KBr) cm^-1: 1550 (C=C ring skeleton Ar. moiety), 1412(C=C ring skeleton pyrimidine moiety), 3220 (N-H), 3302(OH).

¹H NMR (d) in ppm 5.6 (1H, s, NH -2-Pyrrole),6.35-7.2 (2H, s, CH=CH),7.23-7.33 (5H, d, Ar-H), 2.04-2.14 (3H, d, CH₃).

MS m/z (M⁺) 226

 

1-(3,5-Dimethyl-1H-pyrrol-2-yl)-3-(2-fluorophenyl)prop-2-en-1-oneAP3

IR (KBr) cm^-11682.96  ( C=O of α,β unsaturated ketone), 1597.13 (Ar C=C) and 750.69 (C-Cl str.)

¹H NMR (d) in ppm 5.6 (1H, s, NH -2-Pyrrole), 6.35-7.2 (2H, s, CH=CH), 7.23-7.33 (4H, d, Ar-H), 2.04-2.14 (3H, d, CH₃).

MS m/z (M⁺) 244

 

1-(3,5-Dimethyl-1H-pyrrol-2-yl)-3-(2-methoxyphenyl)prop-2-en-1-oneAP5

IR (KBr) cm^-1: 2842.23 cm-1 (Ar C-H str.),1679.11 ( C=O of α,β unsaturated ketone) , 1605.81 (Ar C=C) and 1188.20

C-O-CH₃

¹H NMR (d) in ppm 5.6 (1H, s, NH -2-Pyrrole), 6.35-7.2 (2H, s, CH=CH), 7.23-7.33 (5H, d, Ar-H), 2.04-2.14 (3H, d, CH₃)

 MS m/z (M⁺) 256

 

Antimicrobial Activity:

Microbial growth inhibitory properties of test substances were determined by cup plate method. The drugs were initially dissolved in H₂O₂/DMSO and tested at concentrations of 100μg/ml against all the microorganisms. Sterile nutrient agar plates were prepared and 0.1 ml of the innoculum from standardized culture of test organism was spread uniformly. Wells were prepared by using a sterile borer of diameter 10 mm and 100μl of the test substance, standard antibiotic and the solvent control were added in each well separately. Standard antibiotic, ampicillin was tested against gram negative, gram positive bacteria respectively. The plates were placed at 4ºC for 1 h to allow the diffusion of test solution into the medium and plates were incubated at a temperature optimal for the test organism and for a period of time sufficient for the growth of at least 10 to 15 generations (usually 24 h at 37ºC). The zone of inhibitions of microbial growth around the well was measured in mm.

 

RESULTS AND DISCUSSION

Table 1: Physicochemical data of synthesized Chalcones

S. No	Comp. Code	Mol. Formula	Mol. Wt	M.P°C	Rf value (solvent system)	Physical Nature	% Yield
1	AP 1	C15H14NO	225	142-144	0.36 CH3COOC2H5:C6H12 20:80	Brown Crystal	57
2	AP 2	C15H14ClNO	259	166-168	0.33 CH3COOC2H5:C6H12 20:80	Buff Green Crystal	59
3	AP 3	C15H14FNO	243	150-152	0.30 CH3COOC2H5:C6H12 20:80	Light Yellow Crystal	53
4	AP 4	C16H17NO	239	146-148	0.44 CH3COOC2H5:C6H12 10:90	Pale Yellow Crystal	62
5	AP5	C16H17NO2	255	161-163	0.41 CH3COOC2H5:C6H12 10:90	Yellow Crystal	66

Table 2: Antimicrobial activity data of synthesized compounds.

Comp Code	Anti-bacterial activity (Zone of inhibition in mm)
	B.subtilis	S.aureus	E.coli	P.aeruginosa
AP  1	11	9	7	7
AP2	13	9	10	9
AP3	14	11	11	10
AP4	9	6	5	5
AP5	10	6	5	5
Ampicillin	20	16	17	18

 

Antimicrobial Activity:

Among the screened compounds, AP2 and AP3 have shown good antibacterial activity against gram +ve and gram -ve bacteria compared to the standard drug.

 

CONCLUSION:

This study reports the successful synthesis of substituted phenylpropenone pyrrolyl derivatives with moderate yields and most of the synthesized compounds showed promising antimicrobial activity.

 

ACKNOWLEDGEMENTS:

The authors are thankful to Nitte 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 spectroscopic data.

 

REFERENCES:

1.        M. Liu, P. Wilairat P, M. L. Go, Antimalarial alkoxylated and hydroxylated chalcones [corrected]: structure-activity relationship analysis. J. Med. Chem...2001:44;4433

2.        M. L. Edwards, D. M. Stemerick, P. S. Sunkara, Chalcones: a new class of antimitotic agents. J. Med. Chem., 1990:33: 1948.

3.        F. Bois, C. Beney, A. Boumendjel, A. M. Mariotte, G. Conseil, A. Di. Pietro, Halogenated chalcones with high-affinity binding to P-glycoprotein: potential modulators of multidrug resistance.J. Med. Chem., 1998:41:4161.

4.        Y.-M. Lin, Y. Zhou, M. T. Flavin, L.-M. Zhou, W. Nie, F. - C. Chen, Chalcones and flavonoids as anti-tuberculosis agents. Bioorg. Med. Chem., 2002:10; 2795.

5.        S. F. Nielsen, S. B. Christensen, G. Cruciani, A. Kharazmi, T. Liljefors, Antileishmanial Chalcones:  Statistical Design, Synthesis, and Three-Dimensional Quantitative Structure− Activity Relationship Analysis J. Med. Chem.1998: 41;4819

6.        S. Ducki, R. Forrest, J. A. Hadfield, A. Kendall, N. J. Lawrence, A. T. McGown, D. Rennison, Potent antimitotic and cell growth inhibitory properties of substituted chalcones. Bioorg. Med. Chem. Lett., 1998: 8; 1051.

7.        M. Satyanarayana, P. Tiwari, B. K. Tripathi, A. K. Srivastava, R. Pratap, Synthesis and antihyperglycemic activity of chalcone based aryloxypropanolamines Bioorg. Med. Chem., 2004: 12; 883.

8.        F. Herencia, M. L. Ferrandiz, A. Ubeda, I. Guillen, J. N. Dominguez, J. E. Charris, G. M. Lobo, M. J. Alcaraz, 4-dimethylamino-3',4'-dimethoxychalcone down regulates expression and exerts anti-inflammatory effects. Free Rad. Biol. Med. 2001; 30: 43.

 

 

Accepted on 06.04.2017           © RJPT All right reserved