Synthesis of Quinazoline derivatives and its Antimicrobial Activity

 

 Kajal Pawar, Poonam Kumbhar*, Vishal Shah

Gourishankar Institute of Pharmaceutical Education and Research, Limb, Satara

Survey No.990, NH-4, A/P.-Limb, Tal. and Dist.-Satara- 415015,

 

ABSTRACT:

Heterocyclic rings containing nitrogen atom are important class of compounds for the medicinal chemist. Quinazoline nucleus has attracted attention of medicinal chemists, due to wide spectrum of biological activities shown by them. Synthesis of some 3-substituted-4-(2H)-quinazolinones has been carried out by the reaction of anthranilic acid, formaldehyde and primary aromatic amines. Characterization of compound is carried out by using IR and NMR spectroscopy. Its antimicrobial activity is performed against Staphylococcus aureus using Nutrient Agar Medium. Total four compounds were tested for antimicrobial activity. The compound having nitro group possess maximum antimicrobial activity.

 

 

 

 

INTRODUCTION:

The number of life-threatening infectious diseases caused by multidrug-resistant bacteria has reached an alarming level in many countries around the world. Recently, the Severe^[1] and bird flu caused by avian influenza (H5N1) virus ^[2]have emerged as two important infectious diseases with pandemic potential. Both infections crossed the species barrier to infect humans. Also, the ever growing demand for material protection from microbial contamination is a serious challenge.^[3] The aforementioned facts are a cause of great concern and create a pressing need for new antibacterial agents. Fused pyrimidine ring system is well known to possess important biological properties. Quinazoline and potent antibiotics that are known to inhibit the growth of gram positive bacteria and active transplantable tumors^.[4]

 

This is because quinazolines and their ring-fused derivatives display a broad spectrum of biological activities like anti-tubercular, analgesic, anti-inflammatory and anti-bacterial.^[5]

 

However, search is continuously on to identify a more potent lead molecule as these molecules are developing resistance over a period. Based on the importance of these molecules, our attention was attracted towards synthesis of novel quinazoline derivatives in order to find a more potent molecule. Quinazoline derivatives are synthesized mainly starting from anthranilic acid, benzonitrile^[6] and so on with an appropriate substituent to have specific functionality and activity. The present paper describes the reaction of anthranilic acid and aromatic amines in presence of formaldehyde to get 3-substituted-4-(2H)-quinazolinones. Further synthesized derivatives are screened for the antimicrobial activity by using Staphylococcus aureus.

 

EXPERIMENTAL SECTION:

Procedure:

1)       The equimolar amounts of each of anthranilic acid, formaldehyde and primary aromatic amines were mixed together and dissolved in 25mL of ethanol in round bottomed flask. The resulted mixture was stirred for 10 minutes and refluxed for 5-7 hours.

2)       After the completion of the reaction the flask content was poured into 100ml of cold water to get corresponding 3-substituted-4-(2H)-quinazolinones, in solid state

3)       The products were filtered, washed and dried and recrystallization was carried out by ethanol.^[7]

 

REACTION:

 

Table No. – 1- Percent Yield Of Compound

 

Table No. 2 – Name of Compound  and Reaction Time

 

SPECTROSCOPIC EVALUATION:

Table No:- 3 IR SPECTROSCOPY:

Name of compound	Functional Group	Value
1a	Aromatic CH	3068.75
	C=O	1662.64
	C=N	1697.36
	C-N	1338.6
	NO2	1523.76
1b	Aromatic CH	3061.03
	C=O	1606.7
	C=N	1701.22
	C-N	1359.82
	Br	599.86
1c	Aromatic CH	3061.03
	C=O	1610.56
	C=N	1695.43
	C-N	1363.67
	CH3	1433.11
1d	Aromatic CH	3062.96
	C=O	1664.57
	C=N	1699.29
	C-N	1359.82
	NH2	3477.66

 

Table No. 4- NMR SPECTROSCOPY

Product	δ Value (ppm)
1a	7.483 (s), 7.866 (d), 7.598 (d), 7.486 (d), 7.345 (d) 7.111 (d)
1b	7.932 (s), 7.926 (d), 7.866 (d), 7.799 (d), 7.628 (d), 7.111 (d)
1c	7.956 (s), 7.766 (d), 7.594 (d), 7.486 (d), 7.345 (d) 7.118 (d), 3.568 (s)
1d	7.836 (s), 7.812 (d), 7.933 (d), 7.799 (d), 7.645 (d), 7.120 (d),

 

ANTIMICROBIAL ACTIVITY:

In vitro antibacterial activity was determined by filter paper disc diffusion method by measuring zone of inhibition in mm. All the tested compounds with standard Ciprofloxacin were screened for antibacterial activity against bacterial strains Staphyloccous aureus at a concentration of 10 μg/mL. Nutrient agar was used as culture medium.

 

Dilution of the compounds:

All the synthesized compounds were dissolved in suitable solvent so as to get concentration of 10μg/ml and standard drugs ciprofloxacin of 10μg/ml.

 

Sterilization of equipments and the chemicals:

Nutrient agar medium [NO11], and normal saline solution were sterilized in autoclave at 15Ibs pressure [121⁰C] for 150 mins. Petri plates, Whatman filter paper [41] disc and cotton swabs were sterilized in oven at 160⁰C for 2 hrs.

 

3(4-nitrophenyl)- 4-(3H)-quinazolinone (1a)

 

3(4-bromophenyl)-4-(3H)-quinazolinone (1b)

 

3(2,6diaminophenyl)-4-(3H)-quinazolinone(1c)

 

3(2,6dimethylphenyl)-4-(3H)-quinazolinone (1d)

 

RESULT AND DISCUSSION:

The purpose of this work was to know the synthesis and to obtain different to substituted quinazoline derivatives and screen it for the antimicobial activity. This was achieved by adopting the mentioned method. Quinazolines are prepared by reacting the anthranilic acid with different Primary Amines in presence of formaldehyde and ethanol. The newly synthesized compounds were characterized by IR spectra, melting point, and NMR spectra analysis. By the observation this method proved beneficial for synthesis of quinazoline derivatives.

 

Table no. 5- Antimicrobial Test

Product	Name of compound	Zone of inhibition (mm)
		Standard	Test
1	1a	20	22
2	1b	19.8	18.5
3	1c	21.4	18
4	1d	20	17

 

CONCLUSION:

It is concluded that the new quinazoline derivatives are synthesized successfully. The characterization of synthesized compound was done by IR and NMR spectroscopy.

 

The results of this investigation revealed that the observed increase in antimicrobial activities are attributed to the presence of 4-NO₂, 4-Br, 2, 6-dimethyl and 2,6 diamine in phenyl ring of quinazoline ring of synthesized compounds. Obviously, the comparative evaluation of active compounds will required further studies; the data reported in this article may be helpful guide for the medicinal chemist who is working in this area. Total four compounds were tested for antimicrobial activity, by cup plate method. The compound having nitro group posseses maximum antimicrobial activity.

 

REFERENCE:

1.        Chang, Z., Babiuk, L.A., Hu, J., Therapeutic and prophylactic Potential of small interfering RNAs against severe acute respiratory Syndrome: progress to date. Bio. Drugs. 21, 2007, 9–15.

2.        Gary, W.W.K., Ting, L.F.,. Bird flu: lessons from SARS, Pediatric. Respir. Rev. 8, 2007, 171–176.

3.        Berber, I., Cokmus, C., Atalan, E., Comparison of Staphylococcus spp. cellular and extracellular proteins. Microbiological 72, 2003, 54–59.

4.        Karumanchi Anupama Devi , M. Sarangapani, Sriram, Synthesis and Antimicrobial activity of some Quinazolinones Derivatives, IJDDR, 4, (3) 2012, 324-327.

5.        R Kaur, M Bansal, B Kaur, Synthesis of Some New Quinazoline Derivatives and Theoretical Studies of their Geometries, Chemical Sciences Journal, 18, 2011, 1-9

6.        A.J. Ashcroft, F.E. Davies, G.J. Morgan, Lancet Oncol. 4 (2003) 284-292.

7.        A.D.Mishra. A New Route for the Synthesis of Quinazolinones, Nepal Journal of Science and Technology 12 (2011) 133-138.

 

 

 

 

 

 

Accepted on 29.06.2017           © RJPT All right reserved