SYNTHESIS AND ANTIMICROBIAL STUDIES OF SOME NEW HALOGENATED ISOXAZOLINE DERIVATIVES
HTML Full TextSYNTHESIS AND ANTIMICROBIAL STUDIES OF SOME NEW HALOGENATED ISOXAZOLINE DERIVATIVES
M.M. Kendre, Shahid Shaikh, N.N. Shah and M.A. Baseer*
Organic Chemistry Research Laboratory, Yeshwant Mahavidyalaya, Nanded-431602, Maharashtra, India
ABSTRACT: A series of some new Isoxazoline derivatives derived from 3-(4’-dimethylamino-phenyl)-1-(2-hydroxyphenyl)-Propenone(chalcone) derivatives using hydroxylamine hydrochloride is reported. These newly synthesized compounds were screened for their antimicrobial potencies which reflect moderate to good activity against different strains of bacteria and fungi employed. The promising feature of this reaction is mild reaction condition and excellent yield with high purity of compounds synthesized. All the synthesized compounds were confirmed by IR, 1HNMR and Mass.
Keywords: |
Chalcones, hydroxylamine hydrochloride, Isoxazoline, Antibacterial and Antifungal activities
INTRODUCTION: Compounds incorporating hetero-cyclic ring systems continue to attract considerable interest due to the wide range of biological activities they posses. Amongst them five membered heterocyclic compounds occupy a unique place in the realm of natural and synthetic organic chemistry. Five membered heterocycles like isoxazoline have found wide application as pharmaceutical and agrochemical agents. In recent years, an increasing attention has been given to the synthesis of isoxazoline derivatives as a source of new antibacterial agents. The synthesis of novel isoxazoline derivatives remain a main focus of medicinal research. Isoxazoline represents one of the active classes of compounds possessing a wide spectrum of biological activities.
A large number of isoxazoline derivatives have been found to exhibit antifungal 1-2, antibacterial 3, anticonvulsant 4, ani-inflammatory 5, antiviral 6, analgesic 7-8, antitubercular 9-10 activities. Literature survey revealed that incorporation of halogen (chloro, bromo, iodo) moiety in isoxazoline ring and some fluorinated methyliminobenzoxazoline derivatives have been patented as plant protecting acaricids, fungicides and insecicides 11.
Much research has been carried out with the aim to find their therapeutic values. The derivatives are prepared and tested for variety of biological activities such as antidepressant 12 and hypoglycemic activity 13. Isoxazole derivatives are used as corrosion inhibitors for fuels and lubricants 14. Its derivatives also show a good potency in animal models of thrombosis 15. Penicillin derivatives containing Isoxazoline ring are found to be antibacterial 16.
MATERIALS AND METHODS:
Experimental: All the melting points were determined in open capillary method and are uncorrected. IR spectra were recorded on KBr spectometer.1HNMR spectra on a Bruker Avance DPX 400 MHz spectrometer with CDCl3 as a solvent and TMS internal standard. The chemical shift values are expressed in part per million (ppm) downfield from the internal standard and signals are quoted as s (singlet), d (doublet), t (triplet) and m (multiplet). Purity of the compounds is checked by TLC plates (Merck) using benzene and ethyl acetate as an eluent in the ratio of (7:3 v/v).
General procedure for synthesis of Isoxazolines: A mixture of chalcone (0.01mol) and hydroxylamine hydrochloride (0.01mol) and freshly fused anhydrous sodium acetate (0.02mol) in ethanol were added and the reaction mixture was heated under reflux for 6-7 hr. After completion of reaction (monitored by TLC) the content of the flaks was poured into crushed ice. The separated solid was filtered, washed with water and dried; further purification was done by recrystallization from ethanol. The physical data of synthesized compounds are presented in Table 1.
SCHEME 1
TABLE 1: PHYSICAL DATA OF SYNTHESIZED ISOXAZOLINE DERIVATIVES (3a-j)
Sr.No. | Entry | R1 | R2 | R3 | Molecular formula | Yield (%) | M.P. 0C |
1 | 3a | Cl | H | Cl | C17H16O2Cl2N2 | 90 | 135 |
2 | 3b | I | H | Cl | C17H16O2 ClIN2 | 92 | 130 |
3 | 3c | Br | H | Cl | C17H16O2BrClN2 | 88 | 142 |
4 | 3d | Br | H | Br | C17H16O2Br2N2 | 85 | 122 |
5 | 3e | H | H | Br | C17H17O2BrN2 | 90 | 140 |
6 | 3f | H | CH3 | Cl | C18H19O2ClN2 | 88 | 128 |
7 | 3g | Br | CH3 | Cl | C18H18O2BrClN2 | 86 | 136 |
8 | 3h | I | CH3 | Cl | C18H18O2 IClN2 | 85 | 132 |
9 | 3i | Br | H | CH3 | C18H19O2BrN2 | 87 | 145 |
10 | 3j | I | H | Br | C17H16O2BrIN2 | 92 | 150 |
Antimicrobial activity: Antimicrobial screening of synthesized isoxazoline compounds (3a-j) was conducted by using Cup Plate Method17 at a concentration of 100μg/ml. The bioactivity of these molecules is assessed against different strains of bacteria and fungi as mentioned in Table 2. DMSO was used as solvent control. The results of antimicrobial data are summarized in Table 2. All compounds show the moderate to good activity against bacteria and fungi used.
RESULTS AND DISCUSSION: The structures of the all synthesized compounds 3(a-j) were elucidated on the basis of, IR, 1H-NMR and mass spectroscopy. Presence of aromatic ring was confirmed by absorption band around 3209 cm-1. IR data of all final synthesized compounds confirms the presence of specific functional groups present in the synthesized compounds. The mass and 1HNMR spectra of compounds were in conformity with assigned structures.
As indicated in Table 2, the antimicrobial activity of synthesized compounds is compared to standard drugs, all the synthesized compounds possessed anti-bacterial activity against all the five strains. Compounds 3b, 3c and 3e showed moderate activity against Staphylococcus aureus, Bacillus subtilis, Aspergillus niger and Penicillium chrysogenum as compared to standard drug. Compound 3f, 3i and 3j exhibited good activity against Salmonella typhi, Staphylococcus aureus and Bacillus subtilis.
Spectral data of selected compounds:
3-(3-bromo-5-chloro-2-hydroxy-phenyl)-5-(4’-dimehyl amino-phenyl)-4, 5-dihydro-2-isoxazoline (2c): IR (KBr); 3209 [Ar-C-OH], 2920 [aliphatic C-H] 1612, 1519[C=N], 1098 [C-O-C], 817 cm-1 [N-O];1H NMR; δ 2.85-3.01 (s, 6H,-N(CH3)2), δ 3.41(dd,1H,CHA), δ 3.75 (dd, 1H, CHB), δ 5.69 (t,1H, CHX), δ 10.6 (s,1H,OH) δ 6.70-7.89 (m, 5H, Ar-H ) ppm, Mass (m/z); 394 (m+ ion).
3-(3, 5-dibromo-2-hydroxy-phenyl)-5-(4’-dimethyl amino-phenyl)-4, 5-dihydro-2-isoxazoline (2d): IR (KBr); 3217[Ar-C-OH], 2924 [aliphatic C-H], 1612, 1527 [C=N], 1411 [C=C], 1080[C-O-C], 825 cm-1 [N-O]1H NMR; δ 3.42 (dd, 1H, CHA), δ 3.72(dd, 1H, CHB), δ 5.70 (t, 1H, CHX) δ 2.89-3.09 (s ,6H, (CH3)2), δ 6.72-7.99 ( m, 5H , Ar-H ) δ 10.70 (s, 1H, OH, ) ppm Mass (m/z); 440 (m+ ion).
3-(5-Bromo-2-hydroxy-phenyl)-5-(4’-dimethylamino-phenyl)-4, 5-dihydro-2-isoxazoline (2e): IR (KBr); 3227 [Ar-C-OH], 2921 [Aliphatic C-H], 1608, 1512 [C=N], 1415 {C=C], 1081 [C-O-C], 817 cm-1 [N-O]1H NMR; δ 3.35 (dd, 1H, CHA), δ 3.65 (dd, 1H, CHB), δ 5.72 (t, 1H, CHX), δ 3.1 (s, 6H, (CH3)2), δ 6.70-8.20 (m, 6H, Ar-H), δ 10.75 (s, 1H, OH) ppm Mass (m/z); 361 (m+ ion).
TABLE 2: ANTIMICROBIAL ACTIVITY OF SYNTHESIZED ISOXAZOLINE DERIVATIVES (3a-j)
Products | Bacteria (Zone of Inhibition in mm) | Fungi (Zone of Inhibition in mm) | ||||||
A | B | C | D | E | F | G | H | |
3a | -- | 12 | 21 | 14 | -ve | -ve | -ve | -ve |
3b | -- | 14 | 20 | 17 | -ve | -ve | -ve | -ve |
3c | -- | 12 | 24 | 17 | -ve | -ve | -ve | -ve |
3d | -- | 13 | 21 | 16 | -ve | -ve | -ve | -ve |
3e | -- | 14 | 24 | 14 | -ve | -ve | -ve | -ve |
3f | -- | 12 | 22 | 17 | -ve | -ve | -ve | -ve |
3g | -- | 15 | 21 | 15 | -ve | -ve | -ve | -ve |
3h | -- | 14 | 24 | 15 | -ve | -ve | -ve | -ve |
3i | -- | 16 | 22 | 16 | -ve | -ve | -ve | -ve |
3j | -- | 13 | 21 | 18 | -ve | -ve | -ve | -ve |
A= Escherichia coli, B=Salmonella typhi, C= Staphylococcus aureus, D=Bacillus subtilis; E= Aspergillus niger, F=penicillium chrysogenum, G=Fusarium moneliforme, H= Aspergillus flavus. -- = No Antibacterial activity, -ve = Growth (Antifungal Activity Observed)
CONCLUSION: In conclusion, we have synthesized some new isoxazolines derivatives. The newly synthesized isoxazolines are characterized by spectral data and further evaluated for antimicrobial activity. The results obtained clearly indicate that the synthesized compounds possess significant antibacterial as well as antifungal activity.
ACKNOWLEDGEMENT: The authors are thankful to Principal Yeshwant Mahavidyalaya, Nanded for providing necessary facilities. Authors are thankful to UGC and also to Director IICT Hyderabad for providing spectral analysis facilities for the research work.
REFERENCES:
- Mizabuchis and Satoy: Agri Biol Chem 1984; 48: 2771.
- Bhakunin DS and Chaturvedi R: J Nat Prod 1984; 47: 585.
- Kirilmis C, Ahmedzade M, Suleyman S, Koca M, Kizirgil A: Eur J Med Chem 2008; 43: 300- 308.
- Lapage F and Hublot B: Chem Absr 1996; 113: 211964.
- Shivkumar B and Nargund LVG: Ind J Heterocyclic Chem 1998; 8: 27.
- Simmonds MS, Blaney WM, Mounche FD and Marini Betollo: J Chem Ecol 1996; 16: 365.
- Karabasanagouda T, Airody Vasudeva Adhikari and Girisha: Ind J Chem 2009; 48B: 430-437.
- Nagano M, Sakai J, Mizukai M, Nakamura N, Misaka E, Kobayashi S and Tomita K, Ipn Kokai: 1979; JP54073774: 774 Chem Absr 1980; 92: 41922.
- Kedar RM: Oriental J Chem 1997; 13: 143.
- Kachhadia VV, Patel MR and Joshi HS: J Sci I R Iran 2004; 15(1): 47-51.
- Buethner G, Klonke E, Frohberger E P and Hammann I: Ger Patent, 1973; 221832. Chem Abstr 1974; 86: 14912.
- Malik WU, Mahesh VK, Raishighani M: Ind J Chem 1971; 9: 655.
- Brady BA, Kennedy JA, Sullivan WI: Tetrahedron 1973; 29: 359-362.
- CE Winter, EA Risley and GW Nuss: Proc Soc Exp Bio Med 1962; 111: 544.
- JPD Pinto: J Med Chem 2001; 44: 566.
- Lee SH, Seo GS, Kim JY, Jin XY, Kim HD & Sohn DH: Eur J Pharmacol 2006; 178: 532.
- Banty AL: The Antimicrobial Susceptibility Test: Principle and Practice Ed. by Illus Lea and Febiger Philadelphia, PA, USA 1976; 180.
How to cite this article:
Kendre MM, Shaikh S, Shah NN and Baseer MA: Synthesis and Antimicrobial studies of some new Halogenated Isoxazoline derivatives. Int J Pharm Sci Res 2013; 4(3); 1183-1185.
Article Information
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1183-1185
534KB
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English
IJPSR
M.M. Kendre, Shahid Shaikh, N.N. Shah and M.A. Baseer*
Organic Chemistry Research Laboratory, Yeshwant Mahavidyalaya, Nanded-431602, Maharashtra, India
dr.baseer.nanded@gmail.com
30 November, 2012
29 January, 2013
27 February, 2013
http://dx.doi.org/10.13040/IJPSR.0975-8232.4(3).1183-85
01 March, 2013