Synthesis and Antimicrobial Activity of Some New 2, 4, 6 -Trisubstituted Pyrimidines
N. Srinath1*, Y. Rajendra Prasad2, K. Mukkanti3 and N. K. Agarwal2
1Department of Pharmacy, Acharya Nagarjuna University, Guntur - 521250
2University College of Pharmaceutical Sciences, Andhra University, Visakhapatnam - 530003
3Centre for Pharmaceutical Sciences, J N T University, Hyderabad – 500085
*Corresponding Author E-mail: srinath_n2k@rediffmail.com
ABSTRACT:
A variety of 2-amino-4-(3'-methyl-4'-hydroxyphenyl)-6-(substituted) pyrimidines were synthesized by reacting various chalcones with guanidine hydrochloride. The required chalcones were prepared by condensation of 3'-methyl-4'-hydroxyacetophenone with various substituted aromatic / heteroaromatic aldehydes in the presence of alkali. All these compounds were characterized by IR, 1H NMR and Elemental analysis. The newly synthesized compounds were evaluated for their antimicrobial activity and some of them have shown significant activity when compared with the standard.
KEYWORDS: Pyrimidines, Synthesis, Antimicrobial activity
Among a wide variety of heterocycles that have been explored for developing medicinally important molecules, pyrimidine derivatives occupy an important place in the present day therapeutics. They were reported to possess a broad spectrum of biological activities such as antimicrobial1,2, anti-inflammatory3, anticancer4, antiviral5, antitubercular6 and antimalarial7 properties. These observations prompted the authors to carryout the synthesis of some new 2-amino-4-(3'-methyl-4'-hydroxyphenyl)-6-(substituted) pyrimidines (B1P1 - B15P15), which were evaluated for their antimicrobial activity.
EXPERIMENTAL:
Chemicals and solvents were of reagent grade are used without further purification. Melting points were determined on a capillary melting point apparatus and are uncorrected. 1H NMR spectra were recorded in the indicated solvent on Bruker AMX 400MHz NMR Spectrometer with TMS as internal standard. IR spectra were recorded in KBr on Perkin Elmer – 337 Infrared Spectrophotometer. Microanalyses were performed on Perkin Elmer model 2400 series II apparatus and were within the ± 0.4% of the theoretical values. Column chromatography was performed on silica gel (Merck, 60-120 mesh).
GENERAL PROCEDURE FOR THE PREPARATION OF PYRIMIDINES:
A mixture of chalcones (B1-B15) of 3'-methyl-4'-hydroxyacetophenone (0.001 mol), guanidine hydrochloride (0.001 mol) in absolute ethanol (5 ml) and potassium hydroxide (0.002 mol) were refluxed on a water bath for 6 hours. The solvent was completely evaporated and the residue was poured into ice cold water, the precipitated solid was collected by filtration, purified by column chromatography and crystallized from suitable solvent to give pyrimidine derivatives8-12 (Scheme 1). The chemical and spectral data of the compounds (B1P1 - B15P15) are given in Table 1, Table 2 and Table 3.
ANTIMICROBIAL ACTIVITY
Cup plate method 13,14 using Mueller – Hinton agar medium was employed to study the preliminary antibacterial activity of newly synthesized pyrimidines (B1P1 - B15P15) against B. pumilis, B. subtilis, E. coli and P. vulgaris. The agar medium was purchased from Hi media Laboratories Ltd., Mumbai, India. Preparation of nutrient broth, subculture, base layer medium, agar medium and peptone waster was done as per the standard procedure. Each test compound (5mg) was dissolved in 5 ml of dimethyl sulfoxide (1000 µg/ml). Volumes of 0.05 ml and 0.1 ml of each compound were used for testing.
Same cup plate method using PDA medium was employed to study the preliminary antifungal activity of newly synthesized pyrimidines (B1P1 - B15P15) against A. niger and P. crysogenium.
Scheme 1
Chalcone Guanidine 2, 4, 6 – trisubstituted pyrimidine
(as hydrochloride salt)
(B1 - B15) (B1P1 - B15P15)
Where Ar =
The PDA medium was purchased from Hi media Laboratories Ltd., Mumbai, India. Preparation of nutrient broth, subculture, base layer medium and PDA medium was done as per the standard procedure. Each test compound (5mg) was dissolved in 5 ml of dimethyl sulfoxide (1000 µg/ml). Volumes of 0.05 ml (50µg) and 0.1 ml (100µg) of each compound were used for testing.
The cups each of 7 mm diameter were made by scooping out the medium with a sterilized cork borer in a petridish, which was streaked with the organisms. The solutions of each test compound (0.05 ml and 0.1 ml) were added separately in the cups and petridishes were subsequently incubated. Benzyl penicillin and Fluconazole were used as standard (reference) drugs for evaluation of antibacterial and antifungal activities respectively and dimethyl- sulfoxide as control, which did not reveal any inhibition. Zone of inhibition produced by each compound was measured in mm and the results are presented in Table 4 and Table 5.
Table 1. PHYSICAL CHARACTERIZATION DATA OF PYRIMIDINES
|
Compound |
Ar |
Formula |
m.p (OC) |
Yield (%) |
|
B1P1 |
2''-pyridinyl |
C16H14 N4O (C, H, N) a |
157 |
76 |
|
B2P2 |
3''-pyridinyl |
C16H14 N4O (C, H, N) |
160 |
74 |
|
B3P3 |
4''-pyridinyl |
C16H14 N4O (C, H, N) |
149 |
75 |
|
B4P4 |
2''-furyl |
C15H13 N3O2 (C, H, N) |
173 |
70 |
|
B5P5 |
2''-pyrrolyl |
C15H14 N4O (C, H, N) |
159 |
72 |
|
B6P6 |
2''-thienyl |
C15H13 N3SO (C, H, N) |
162 |
78 |
|
B7P7 |
2''-indolyl |
C19H16 N4O (C, H, N) |
195 |
68 |
|
B8P8 |
2''-quinolinyl |
C20H16 N4O (C, H, N) |
183 |
70 |
|
B9P9 |
9''-anthracenyl |
C25H19 N3O (C, H, N) |
170 |
66 |
|
B10P10 |
4''-fluorophenyl |
C17H14 N3FO (C, H, N) |
260 |
71 |
|
B11P11 |
4''-chlorophenyl |
C17H14 N3ClO (C, H, N) |
145 |
73 |
|
B12P12 |
4''-bromophenyl |
C17H14 N3BrO (C, H, N) |
252 |
70 |
|
B13P13 |
4''-methylphenyl |
C18H17 N3O (C, H, N) |
110 |
66 |
|
B14P14 |
4''-methoxyphenyl |
C18H17 N3O2 (C, H, N) |
155 |
68 |
|
B15P15 |
3'',4'',5''-trimethoxyphenyl |
C20H21 N3O4 (C, H, N) |
165 |
72 |
|
a Elemental analysis for C, H, N are within ± 0.4% of theoretical values |
||||
Table 2. IR SPECTRAL DATA OF PYRIMIDINES
|
Compound |
Position of absorption band ( cm-1) |
|
B1P1 |
3361 (NH2), 3499 (O-H), 1602 (C=N), 1573 (C=C Quadrant of Ar), 1508 (CH=CH) |
|
B2P2 |
3362 (NH2), 3497 (O-H), 1600 (C=N), 1575 (C=C Quadrant of Ar),1505 (CH=CH) |
|
B3P3 |
3364 (NH2), 3496 (O-H), 1602 (C=N), 1572 (C=C Quadrant of Ar), 1504 (CH=CH) |
|
B4P4 |
3360 (NH2), 3498 (O-H), 1602 (C=N), 1573 (C=C Quadrant of Ar), 1504 (CH=CH), 1200 (-C-O-) |
|
B5P5 |
3365 (NH2), 3499 (O-H), 1605 (C=N), 1574 (C=C Quadrant of Ar), 1505 (CH=CH) |
|
B6P6 |
3361 (NH2), 3497 (O-H), 1602 (C=N), 1572 (C=C Quadrant of Ar), 1504 (CH=CH), 704 (C-S) |
|
B7P7
|
3365 (NH2), 3495 (O-H), 1604 (C=N), 1575 (C=C Quadrant of Ar), 1506 (CH=CH) |
|
B8P8 |
3361 (NH2), 3496 (O-H), 1603 (C=N), 1570 (C=C Quadrant of Ar),1503 (CH=CH) |
|
B9P9 |
3363 (NH2), 3495 (O-H), 1601 (C=N), 1573 (C=C Quadrant of Ar), 1504 (CH=CH) |
|
B10P10 |
3361 (NH2), 3498 (O-H), 1605 (C=N), 1574 (C=C Quadrant of Ar), 1505 (CH=CH), 1120 (C-F) |
|
B11P11 |
3360 (NH2), 3496 (O-H), 1600 (C=N), 1572 (C=C Quadrant of Ar), 1505 (CH=CH), 853 (C-Cl) |
|
B12P12 |
3362 (NH2), 3499 (O-H), 1604 (C=N), 1575 (C=C Quadrant of Ar), 1506 (CH=CH), 1020 (C-Br) |
|
B13P13 |
3360 (NH2), 3497 (O-H), 1603 (C=N), 1572 (C=C Quadrant of Ar), 1505 (CH=CH) |
|
B14P14 |
3361 (NH2), 3495 (O-H), 1602 (C=N), 1571 (C=C Quadrant of Ar), 1507 (CH=CH), 1070 (-O-CH3) |
|
B15P15 |
3365 (NH2), 3498 (O-H), 1604 (C=N), 1570 (C=C Quadrant of Ar), 1504 (CH=CH), 1072 (-O-CH3) |
RESULTS AND DISCUSSION:
From the results, it is evident that the compounds B8P8, B4P4 and B10P10 exhibited moderate antibacterial activity, at a concentration of 0.1ml dose level and is comparable to that of standard drug, benzyl penicillin at a concentration of 100 µg/ml. The other compounds also showed antibacterial activity less when compared to other pyrimidine derivatives. Compounds B10P10, B11P11 and B12P12 exhibited moderate antifungal activity and are comparable to that of fluconazole. The results are consistent with the biological activity of the existing drugs. Further studies have to be conducted to explore the mechanism of action of these compounds.
Table 3. 1H NMR SPECTRAL DATA OF PYRIMIDINES
|
Compound |
Chemical shift ( δ ) in ppm |
|
B1P1 |
8.28 (1H,s, C-5-H),5.40 (2H,s, C-2-NH2) 7.87 (1H,s,C-2'-H),2.32 (3H,s,C-3'-CH3) 7.20 (1H,d,J=8.8Hz,C-5'-H),7.90 (1H,d,J=8.8Hz,C-6'-H) 8.57 (1H,d,J=8Hz,C-3''-H),7.67 (1H,t,J=8Hz,C-4''-H) 7.47 (1H,m,J=7.5Hz,C-5''-H),8.68 (1H,d,J=7.8Hz, C-6''-H) |
|
B2P2 |
7.71 (1H,s, C-5-H),5.30 (2H,s, C-2-NH2) 7.84 (1H,s,C-2'-H),2.32 (3H,s,C-3'-CH3) 7.20 (1H,d,J=8.8Hz,C-5'-H),7.94 (1H,d,J=8.8Hz,C-6'-H) 9.19 (1H,s,C-2''-H),8.31 (1H,d,J=8.2Hz,C-4''-H) 7.42 (1H,m ,J=8.2Hz,C-5''-H),8.69 (1H,d,J=7.8Hz, C-6''-H) |
|
B3P3 |
7.86 (1H,s, C-5-H),5.30 (2H,s, C-2-NH2) 7.83 (1H,s,C-2'-H),2.33 (3H,s,C-3'-CH3) 7.20 (1H,d,J=8.8Hz,C-5'-H),7.94 (1H,d,J=8.8Hz,C-6'-H) 8.75 (1H,d, J=8.1Hz ,C-2''-H),7.93 (1H,d,J=8.1Hz,C-3''-H) 8.09 (1H,d ,J=8.1Hz,C-5''-H),8.61 (1H,d,J=8.2Hz, C-6''-H) |
|
B4P4 |
8.00 (1H,s, C-5-H),5.25 (2H,s, C-2-NH2),7.83 (1H,s,C-2'-H) 2.32 (3H,s,C-3'-CH3),7.20 (1H,d,J=8.8Hz,C-5'-H) 7.87 (1H,d,J=8.8Hz,C-6'-H),7.00 (1H,d, J=6.8Hz ,C-3''-H) 7.41 (1H,d,J=6.7Hz,C-4''-H),7.70 (1H,d,J=6.7Hz,C-5''-H) |
|
B5P5 |
7.80 (1H,s, C-5-H),5.30 (2H,s, C-2-NH2),7.77 (1H,s,C-2'-H) 2.32 (3H,s,C-3'-CH3),7.20 (1H,d,J=8.8Hz,C-5'-H) 8.00 (1H,d,J=8.8Hz,C-6'-H),6.87 (1H,d, J=6.7Hz ,C-3''-H) 6.18 (1H,m,J=6.8Hz,C-4''-H),6.69 (1H, d, J=6.7Hz,C-5''-H) |
|
B6P6 |
7.40 (1H,s, C-5-H),5.18 (2H,s, C-2-NH2),7.82 (1H,s,C-2'-H) 2.32 (3H,s,C-3'-CH3),7.20 (1H,d,J=8.8Hz,C-5'-H) 7.90 (1H,d,J=8.8Hz,C-6'-H),7.89 (1H,d, J=6.6Hz ,C-3''-H) 7.21 (1H,m,J=6.7Hz,C-4''-H),7.57 (1H, d, J=6.6Hz,C-5''-H) |
|
B7P7 |
7.38 (1H,s, C-5-H),5.44 (2H,s, C-2-NH2),7.86 (1H,s,C-2'-H) 2.32 (3H,s,C-3'-CH3),7.15 (1H,d,J=8.8Hz,C-5'-H) 7.91 (1H,d,J=8.8Hz,C-6'-H),8.21 (1H,m,C-2''-H) 8.60 (1H,d,J=7.7Hz,C-4''-H),7.05 (1H,t, J=7.7Hz,C-5''-H) 7.22 (1H,t, J=7.9Hz,,C-6''-H),7.44 (1H,d, J=7.9Hz,C-7''-H) |
|
B8P8 |
8.31 (1H,s, C-5-H),5.35 (2H,s, C-2-NH2), 7.87 (1H,s,C-2'-H),2.32 (3H,s,C-3'-CH3) 7.20 (1H,d,J=8.8Hz,C-5'-H),7.90 (1H,d,J=8.8Hz,C-6'-H) 8.50 (1H,d, J=8.1Hz, C-3''-H),8.30 (1H,d,J=8.1Hz,C-4''-H) 7.85(1H,d, J=7.9Hz,C-5''-H),7.55 (1H,t, J=7.9Hz,C-6''-H) 7.73 (1H,t, J=7.9Hz,C-7''-H),8.26 (1H,d,J=7.9Hz, C-8''-H) |
|
B9P9 |
7.82 (1H,s, C-5-H),5.02 (2H,s, C-2-NH2),7.90 (1H,s,C-2'-H) 2.32 (3H,s,C-3'-CH3),7.10 (1H,d,J=8.8Hz,C-5'-H) 7.91 (1H,d,J=8.8Hz,C-6'-H),7.81 (1H,d, J=7.8Hz ,C-1''-H) 7.18 (1H,m, J=8.1Hz ,C-2''-H),7.48 (1H,m, J=8.1Hz ,C-3''-H) 8.23 (1H,d,J=8.1Hz,C-4''-H),8.23 (1H,d, J=8.1Hz,C-5''-H) 7.48 (1H,m, J=8.1Hz,C-6''-H),7.18 (1H,m, J=7.8Hz,C-7''-H) 7.82 (1H,d,J=7.8Hz, C-8''-H),8.70 (1H,s, C-10''-H) |
|
B10P10 |
7.84 (1H,s, C-5-H),5.45 (2H,s, C-2-NH2), 7.84 (1H,s,C-2'-H),2.32 (3H,s,C-3'-CH3) 6.89 (1H,d,J=8.8Hz,C-5'-H),7.94 (1H,d,J=8.8Hz,C-6'-H) 8.10 (1H,d,J=8.6Hz,C-2''-H),7.29 (1H,d,J=8.6Hz,C-3''-H) 7.29 (1H,d, J=8.6Hz,C-5''-H),7.99 (1H,d, J=8.6Hz,C-6''-H) |
|
B11P11 |
7.81 (1H,s, C-5-H),5.42 (2H,s, C-2-NH2) 7.84 (1H,s,C-2'-H),2.32 (3H,s,C-3'-CH3) 7.15 (1H,d,J=8.8Hz,C-5'-H),7.94 (1H,d,J=8.8Hz,C-6'-H) 7.85 (1H,d,J=8.4Hz,C-2''-H),7.60 (1H,d,J=8.4Hz,C-3''-H) 7.60 (1H,d, J=8.4Hz,C-5''-H),7.99 (1H,d, J=8.4Hz,C-6''-H) |
|
B12P12 |
7.79 (1H,s, C-5-H),5.30 (2H,s, C-2-NH2) 7.84 (1H,s,C-2'-H),2.32 (3H,s,C-3'-CH3) 7.30 (1H,d,J=8.8Hz,C-5'-H),7.94 (1H,d,J=8.8Hz,C-6'-H) 8.12 (1H,d,J=8.2Hz,C-2''-H),7.53 (1H,d,J=8.2Hz,C-3''-H) 7.53 (1H,d, J=8.2Hz,C-5''-H),8.12 (1H,d, J=8.2Hz,C-6''-H) |
|
B13P13 |
7.72 (1H,s, C-5-H),5.43 (2H,s, C-2-NH2),7.84 (1H,s,C-2'-H) 2.32 (3H,s,C-3'-CH3),6.89 (1H,d,J=8.8Hz,C-5'-H) 7.94 (1H,d,J=8.8Hz,C-6'-H),8.05 (1H,d,J=8.1Hz,C-2''-H) 7.36 (1H,d,J=8.1Hz,C-3''-H),2.41 (3H,s, C-4''-CH3) 7.36 (1H,d, J=8.1Hz,C-5''-H),8.05 (1H,d, J=8.1Hz,C-6''-H) |
|
B14P14 |
7.75 (1H,s, C-5-H),5.45 (2H,s, C-2-NH2),7.84 (1H,s,C-2'-H) 2.32 (3H,s,C-3'-CH3),7.10 (1H,d,J=8.8Hz,C-5'-H) 7.94 (1H,d,J=8.8Hz,C-6'-H),8.10 (1H,d,J=7.9Hz,C-2''-H) 7.05 (1H,d,J=7.9Hz,C-3''-H),3.80 (3H,s, C-4''-OCH3); 7.05 (1H,d, J=7.9Hz,C-5''-H),7.99 (1H,d, J=7.9Hz,C-6''-H) |
|
B15P15 |
7.57 (1H,s, C-5-H),5.25 (2H,s, C-2-NH2),7.84 (1H,s,C-2'-H); 2.32 (3H,s,C-3'-CH3),7.15 (1H,d,J=8.8Hz,C-5'-H) 7.94 (1H,d,J=8.8Hz,C-6'-H),7.61 (1H,s,C-2''-H); 3.93 (3H,s,C-3''-OCH3),3.94 (3H,s, C-4''-OCH3) 3.93 (3H,s, C-5''-OCH3),7.61 (1H,s, C-6''-H) |
|
* s, singlet; d, doublet; m, multiplet |
|
Table 4. ANTIBACTERIAL ACTIVITY OF PYRIMIDINE DERIVATIVES
|
Compound
|
Ar |
Zone of inhibition in mm |
|||||||
|
Quantity in µg/ml |
|||||||||
|
B. pumilis |
B. subtilis |
E. coli |
P. vulgaris |
||||||
|
50 |
100 |
50 |
100 |
50 |
100 |
50 |
100 |
||
|
B1P1 |
2''-pyridinyl |
04 |
06 |
05 |
07 |
05 |
09 |
09 |
10 |
|
B2P2 |
3''-pyridinyl |
04 |
05 |
05 |
06 |
05 |
07 |
08 |
09 |
|
B3P3 |
4''-pyridinyl |
05 |
06 |
05 |
07 |
06 |
08 |
08 |
10 |
|
B4P4 |
2''-furyl |
12 |
14 |
13 |
17 |
15 |
17 |
13 |
15 |
|
B5P5 |
2''-pyrrolyl |
05 |
08 |
06 |
09 |
07 |
11 |
09 |
12 |
|
B6P6 |
2''-thienyl |
05 |
07 |
05 |
08 |
06 |
10 |
10 |
11 |
|
B7P7 |
2''-indolyl |
09 |
12 |
10 |
13 |
13 |
16 |
10 |
12 |
|
B8P8 |
2''-quinolinyl |
13 |
15 |
14 |
17 |
16 |
18 |
14 |
16 |
|
B9P9 |
9''-anthracenyl |
04 |
05 |
04 |
05 |
05 |
06 |
07 |
08 |
|
B10P10 |
4''-fluorophenyl |
12 |
15 |
13 |
16 |
16 |
17 |
12 |
15 |
|
B11P11 |
4''-chlorophenyl |
11 |
14 |
12 |
16 |
15 |
16 |
12 |
14 |
|
B12P12 |
4''-bromophenyl |
10 |
14 |
12 |
15 |
14 |
16 |
11 |
13 |
|
B13P13 |
4''-methylphenyl |
06 |
09 |
08 |
11 |
09 |
14 |
09 |
11 |
|
B14P14 |
4''-methoxyphenyl |
05 |
09 |
07 |
10 |
08 |
13 |
09 |
10 |
|
B15P15 |
3'',4'',5''-trimethoxyphenyl |
07 |
10 |
08 |
12 |
10 |
15 |
08 |
12 |
|
Benzyl penicillin(standard) |
15 |
18 |
16 |
19 |
18 |
22 |
17 |
20 |
|
|
Control (DMSO) |
- |
- |
- |
- |
- |
- |
- |
- |
|
Table 5. ANTIFUNGAL ACTIVITY OF PYRIMIDINE DERIVATIVES
|
Compound |
Ar |
Zone of inhibition in mm |
|||
|
Quantity in µg/ml |
|||||
|
A. niger |
P. crysogenium |
||||
|
50 |
100 |
50 |
100 |
||
|
B1P1 |
2''-pyridinyl |
04 |
05 |
05 |
07 |
|
B2P2 |
3''-pyridinyl |
04 |
06 |
05 |
06 |
|
B3P3 |
4''-pyridinyl |
04 |
05 |
06 |
07 |
|
B4P4 |
2''-furyl |
09 |
12 |
08 |
10 |
|
B5P5 |
2''-pyrrolyl |
05 |
07 |
05 |
06 |
|
B6P6 |
2''-thienyl |
05 |
06 |
05 |
07 |
|
B7P7 |
2''-indolyl |
08 |
11 |
07 |
09 |
|
B8P8 |
2''-quinolinyl |
10 |
12 |
09 |
11 |
|
B9P9 |
9''-anthracenyl |
04 |
05 |
05 |
06 |
|
B10P10 |
4''-fluorophenyl |
13 |
16 |
12 |
14 |
|
B11P11 |
4''-chlorophenyl |
12 |
15 |
12 |
13 |
|
B12P12 |
4''-bromophenyl |
11 |
14 |
11 |
12 |
|
B13P13 |
4''-methylphenyl |
06 |
09 |
06 |
07 |
|
B14P14 |
4''-methoxyphenyl |
05 |
08 |
06 |
07 |
|
B15P15 |
3'',4'',5''-trimethoxyphenyl |
07 |
10 |
07 |
08 |
|
Fluconazole (standard) |
17 |
21 |
15 |
18 |
|
|
Control (DMSO) |
- |
- |
- |
- |
|
REFERENCES:
1. A.K. Padhy, M.Bardham and C.S.Danda, Indian J. Chem., 42B(4), 910 (2003).
2. K.H. Nakum and V.H.Shah, Indian J.Het.Chem., 12(1), 37 (2002).
3. B.M. Basavaraja, V.P.Vaidya and Y.S.Agasimundin, Indian J.Het.Chem., 15(1), 1 (2005).
4. N.S. Habib, R.Soliman, K.Ismail and A.M.Hussan, Boll.Chem.Farmaceutico, 142(9), 396 (2003).
5. M.S.Novikov,A.A.Ozerov,Y.A.Orlova and R.W.Buckheit, Chem.Het.Comp., 41(5), 625 (2005).
6. T.Y.Pasha, R.H.udupi and A.R.Bhat, Indian J.Het.Chem., 15(2),149 (2005).
7. A.Agarwal, K.Srivastawa, S.K.Puri, S.Sinha and M.S.P.Chauhan, Bioorg.Med.Chem.Lett., 15(22), 4923 (2005).
8. Reddy, C.S. and Nagaraj, A., J. Heterocycl. Chem., 44, 1181 (2007).
9. Suryawanshi, S.N., Bhat, B.A., Susmita, P., Naveen, C. and Suman, G., Eur. J. Med. Chem., 42, 1211 (2007).
10. Chauhan, P.M.S., Naresh, S., Agarwal, A., Sanjay babu, K., Nishi, N. G. and Suman, G., Bioorg. Med. Chem., 14, 7706 (2006).
11. Akbar, M., Naser, F., Golnar, K. and Neda, F., Synthesis and Reactivity in Inorganic, Metal-Organic and Nano-Metal Chemistry, 37, 279 (2007).
12. Shujang, Tu, Fang, F., Chunbao, M., Hong, J., Youjian, F., Daqing, S. and Xiangshan, W., Tetrahedron Lett., 44, 6153 (2003).
13. A.L.Banty, The Antimicrobial Susceptibility Test; Principle and Practice, edited by Illus Lea and Febiger, (Philadelphia,USA), 180 (1976).
14. H.W.Seely and P.J.Van Dermark, Microbes in Action: A Laboratory manual of Microbiology, D.B.Taraporewala Sons and Co., Bombay, (1975) pp.55-80.
Received on 06.12.2010 Modified on 18.12.2010
Accepted on 25.12.2010 © AJRC All right reserved
Asian J. Research Chem. 4(2): February 2011; Page 329-333