Microwave-Assisted Synthesis of N-Alkylated

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The synthesis of bibenzoimidazole derivatives was car- ried out by .... bearing methyl benzoate group and nitrile group at 4-benzyl ..... amidine groups. Bioorg.
380

Letters in Drug Design & Discovery, 2009, 6, 380-386

Microwave-Assisted Synthesis of Derivatives: Antimicrobial Studies

N-Alkylated

Bibenzoimidazolyl

S. Nanjunda Swamya,b, C.V. Kavithaa, B.S. Priyaa, S.L. Gaonkara, M.V. Tejesvic and K.S. Rangappa*,a a

Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore- 570006, Karnataka, India

b

Department of Biotechnology, Sri Jayachamarajendra College of Engineering, Mysore-570006, Karnataka, India

c

Department of Studies in Biotechnology, University of Mysore, Manasagangotri, Mysore-570 006, Karnataka, India Received February 14, 2009: Revised March 17, 2009: Accepted March 19, 2009

Abstract: The purpose of this study was to evaluate the efficacy of newly synthesized bibenzoimidazolyl derivatives 2(ai) as antimicrobials. These molecules are obtained by the reaction of different pharmaceutically important bioactive aralkyl halides with 1, 7 -dimethyl-2'-propyl-1H, 3'H-[2, 5 ]bibenzoimidazole in presence of powdered potassium carbonate in DMF solvent under both conventional and microwave methods. The microwave method offers the products 2(a-i) in higher yields compared to conventional method. All the synthesized compounds were characterized by IR, 1H NMR and elemental analysis and evaluated their efficacy as antimicrobials. We observed the significant differences between the antimicrobial activities of the newly synthesized compounds based on their various substituents present at N1 position. Compounds 2h, 2a, 2c, 2e and 2f showed potent antimicrobial activity compared to standard drugs.

Keywords: Bibenzoimidazole, N-alkylation, Microwave, Antimicrobials. INTRODUCTION Development of novel therapeutics for the treatment of bacterial infection has become a clinical imperative. The greatest threat to current antibiotic coverage is the rapid evolution and spread of drug-resistance, which has now been reported against every currently available antibiotics. A solution to this dilemma is to develop a broad range of lead compounds for clinical trials. Synthetic combinatorial libraries made up of hundreds to millions of small organic molecules have been successfully developed and used to discover new antimicrobial leads. Therefore, there is a pressing need to develop new antibiotics and novel antimicrobial agents. Benzimidazole nucleus is important pharmacophore in drug discovery [1]. Since they are commonly encountered in drugs that display diverse pharmacological activities such as anti-inflammatory [2], histamine-H3 antagonist [3], antioxidant [4], gastroprotective [5], antitumoral, antiparasitic, antimicrobial [6], antihelmintic [7], insecticidal, herbicidal [8] and are active as human topoisomerase I (topo I) poisons [911]. Further substituted biphenyls and benzoimidazole compounds have been found to exhibit antihypertensive activity [12, 13]. Recently, the synthesis of novel near-linear biphenyl benzimidazole dication derivatives and their initial evaluation as minor groove binders and anti-protozoan agents [14] has been reported. A series of 2 heterocyclic derivatives of 5-phenyl-2, 5 1H-bibenzimidazoles were evaluated for topoisomerase I poisoning activity and cytotoxicity [15]. The compound 1,7'-dimethyl-2'-propyl-1H, 3'H-[2,5 ]bibenzoimidazole is an intermediate for the synthesis of telmisartan (tel-mi-SAR-tan), which is an angiotensin *Address correspondence to this author at the DOS in Chemistry, University of Mysore, 570006, India; Tel: +91- 821-2412191; Fax: +91-821-2412191; E-mail: [email protected] 1570-1808/09 $55.00+.00

II receptor antagonists to treat hypertension [16]. In recent developments, the use of Microwave irradiation (MW) to simplify and improve classic organic reactions has become a very popular method [17-19], because it often leads to higher yields, cleaner reactions and shorter reaction times. In connection with solvent-free conditions, MW methods result in efficient and safe technology, “Green Chemistry” [20]. Earlier we have reported the synthesis of bioactive heterocycles [21-23] and N-alkylation of benzotriazole derivatives [24] under both conventional and microwave irradiation method. Herein, we report the N-alkylation of 1,7'-dimethyl-2'propyl-1H,3'H-[2,5 ]bibenzoimidazole derivatives bearing key intermediates under both conventional and microwave irradiation method and checked their efficacy as antimicrobials. RESULTS AND DISCUSSION The synthesis of bibenzoimidazole derivatives was carried out by using equimolar mixture of 1,7’-dimethyl-2'propyl-1H, 3'H-[2,5 ]bibenzoimidazole and aralkyl halides in DMF solution in the presence of 3 equivalents of powdered potassium carbonate as a base (Scheme 1). The title compounds are also obtained by microwave technique by taking the mixture of 1,7'-dimethyl-2'-propyl-1H, 3'H-[2,5 ]bibenzoimidazole and aralkyl halides in 3 volumes of DMF at 60% power for 30-40 sec. The yields obtained by conventional and microwave irradiation methods were in the range of 60-65% and 80-85% (Table 1) respectively. The title compounds were synthesized in two different methods viz conventional and microwave. In comparison to conventional method, microwave method offers more advantages such as reduced reaction time (50-60s), low cost, simplicity in processing, reduced pollution and high yield. © 2009 Bentham Science Publishers Ltd.

Antimicrobial Studies

Letters in Drug Design & Discovery, 2009, Vol. 6, No. 5

381

N N N N N

N

R-X Powdered K2CO3/DMF/ MW. irr

N

N

R

H

1

2(a-i)

O

Br

O N

Where, R= MeO

CN

O OMe

2b

2a

O

NO2 2d

2c

2e

O N

N N

O

N

O O O

Cl

2f

2i

2h

2g

Scheme 1. Table 1.

Reaction Conditions and Physical Data of Bibenzoimidazolyl Derivatives

Compound

Reaction Time

R

2a

Yield (%)

mpoC

Conventional (hrs)

MW irr. (S)

Conventional

MW irr.

6

50

65

80

135-137

5

55

60

82

122-125

6

55

65

84

165-166

6

60

62

83

120-123

CN

Br 2b

MeO OMe

2c NO2 O N

2d O

382 Letters in Drug Design & Discovery, 2009, Vol. 6, No. 5

Nanjunda Swamy et al. (Table 1). Contd…..

R

Compound

Reaction Time

mpoC

Yield (%)

Conventional (hrs)

MW irr. (S)

Conventional

MW irr.

6

50

65

85

98-100

5

50

60

83

112-113

5

60

63

80

90-92

5

50

63

81

102-104

6

55

65

85

105-106

O 2e

O O 2f

Cl

N

N 2g

N

2h

N

O O

2i

O O

IR, 1H NMR and elemental analysis characterized all the synthesized compounds. IR spectrum of all the synthesized compounds showed band in the region 3000-3050 cm-1 and 2960-2990 cm-1due to aromatic C-H stretch and aliphatic CH stretch respectively. The band in the region 1410-1420 cm1 may be due to C=N group. In 2a the band at 2210 cm-1 indicates the presence of -CN group. In 2d the band at 1695 cm-1 is due to carbonyl group of cyclic amide. Compound 2f showed the band at 1715 cm-1 which indicates the presence of carbonyl group. 1H NMR spectra of all the compounds showed singlet for three protons in the region 2.5-2.8 ppm and 3.4-3.8 ppm which are due to N-CH3 and Ar-CH3 groups respectively which are present on benzimidazole ring. All compounds except 2d showed a singlet for two protons in the region 5.5-5.95 ppm is due to the CH2, which is attached to imidazole nitrogen atom. In 2h a singlet at 3.93 ppm is due to -OCH3 group and in 2i a singlet for nine protons indicates the tertiary butyl group. All other substituents and aro-

matic protons are observed in the expected region. The formation of the products was further supported by elemental analyses. In Vitro Evaluation of Antimicrobial Activity In an approach to develop new antimicrobial agents, a new series of bibenzoimidazolyl derivatives 2(a-i) were synthesized and evaluated for their efficacy as antimicrobials in vitro by disk diffusion method against different strains. Nystatin was used as standard drug against fungi, streptomycin and tetracycline against bacteria. In all the determinations, tests were performed in triplicate and the results were reported as mean of at least three determinations. Our results showed that the compounds 2h, 2a, 2c, 2e, 2f were effective compared to standard drugs against the bacterial strains tested as shown in Table 2. Antibacterial activity

Antimicrobial Studies

Table 2.

Letters in Drug Design & Discovery, 2009, Vol. 6, No. 5

383

Inhibitory Zone (Diameter) mm of Compounds Against Tested Bacterial Strains by Disk Diffusion Method Inhibitory Zone (diameter) mm a

Compounds Bacillus substilis

Escherichia coli

Pseudomonas fluorescens

Xanthomonas campestrisp vs.

Xanthomonas oryzae

2a

301.2

381.6

401.7

311.0

341.0

2b

120.4

130.5

150.5

140.4

100.2

2c

281.1

371.6

381.7

291.2

331.4

2d

110.4

140.4

160.6

130.4

120.5

2e

261.0

351.1

361.5

271.0

311.1

2f

240.9

301.0

311.0

240.9

290.9

2g

120.4

160.4

180.8

140.5

130.5

2h

321.3

411.9

441.9

331.2

371.6

2i

110.3

150.6

170.7

120.5

110.3

Streptomycin

16 0.5

200.6

230.8

-

-

Tetracycline

-

-

-

180.6

170.5

Streptomycin sulphate (10 g/disc); Tetracycline (10 g/disc) were used as positive reference and Compounds (25 g/disc). a Values are means of three determinations, the ranges of which are less than 5% of the mean in all cases.

shown by the compounds were in the following order 2h 2a 2c 2e 2f. Among the biphenyl series of compounds, 2h and 2a bearing methyl benzoate group and nitrile group at 4-benzyl ring respectively showed good inhibitory activity, while the compounds 2g and 2i did not show any significant antibacterial activity irrespective of the presence of biphenyl moieties. Because of the presence of more bulky group, which might hinder the activity. Compounds 2c, 2e and 2f bearing nitro, benzo[d][1,3] dioxole group and phenacyl groups respectively exhibited significant antibacterial activity. Compounds 2b and 2d were not effective against any of the bacteria tested. From the results of the present study, more substitution lead to less antimicrobial activity. Antifungal activity of the compounds were in the following order 2c2e2f 2h2a. The compounds 2c, 2e and 2f Table 3.

EXPERIMENTAL SECTION The melting points were determined on SELACO-650 hot stage apparatus and are uncorrected. IR (KBr) spectra were recorded on a Jasco FT/IR-4100 Fourier transform infrared spectrometer, 1H NMR were recorded on Shimadzu AMX 400, spectrometer by using CDCl3 as solvent and TMS as an internal standard (Chemical shift in ppm). Elemental

Inhibitory Zone (Diameter) mm of Compounds Against Tested Fungal Strains by Disk Diffusion Method Inhibitory Zone (diameter) mma

Compound

2a

showed more potency than 2h and 2a. This indicates that the bibenzoimidazole derivatives posses better anti-fungal activity, when they are substituted with less and highly reactive functional groups rather than a bulkier substituents. Compounds 2i, 2g, 2b and 2d were not effective against any of the fungal strains tested which might be possibly due to the substitution with the bulkier hydrophobic groups at first position. The antimicrobial activities of the synthesized compounds are shown in Tables 2 and 3.

Aspergillus niger

Aspergillus flavus

Fusarium oxysporum

Trichoderma species

Fusarium monaliforme

200.8

190.75

260.9

281.1

301.2

2b

20.0

40.1

30.1

20.0

50.15

2c

291.2

311.35

381.6

411.8

391.8

2d

40.1

10.0

40.1

50.2

20.0

2e

271.2

281.1

351.4

391.6

361.5

2f

250.8

240.6

321.3

351.5

341.3

2g

70.2

80.2

90.3

40.1

50.1

2h

230.6

210.4

291.1

311.1

321.3

2i

60.2

40.1

10.0

20.0

30.1

Nystatin

140.5

160.5

180.6

200.7

190.6

Nystatin (10 g/disc) was used as positive reference and compounds (25 g/disc). a Values are means of three determinations, the ranges of which are less than 5% of the mean in all cases.

384 Letters in Drug Design & Discovery, 2009, Vol. 6, No. 5

analyses were obtained on a vario-EL instrument. Thin layer chromatography (TLC) was conducted on 0.25 mm silica gel plates (60F254, Merck). All extracted solvents were dried over anhydrous Na2SO4 and evaporated with a BUCHI rotary evaporator. Reagents were obtained commercially and used as received. General Procedure for the Synthesis of 1,7'-Dimethyl-2'propyl-1H-[2,5']bibenzoimidazolyl-3'-ylmethyl Derivatives 2(a-i) Method-1: Conventional Method A mixture of bibenzoimidazole 1 (1eq), alkyl halides (1eq) and powdered potassium carbonate (3 eq) in dimethylformamide (10 ml) were stirred at room temperature for about 5-6 hours till the reaction completes, which was monitored by TLC. After completion of the reaction, the reaction mass was poured into 10 volumes of water, the product was extracted in ethyl acetate (6 volumes x 3), the combined organic layer was washed with water and dried over anhydrous sodium sulphate. The crude products were obtained on evaporation of the solvent under reduced pressure. The crude product was purified by ethanol- n-hexane mixture to get pure product 2(a-i). Method 2: Microwave Irradiation Method A 25 ml conical flask was charged with equimolar mixture of bibenzoimidazole 1, different aralkyl halides, and DMF (10 ml), was irradiated in the microwave oven at 60% power for 50-60s. After completion of the reaction (tlc), the dark red mass was poured into ice-cold water and worked up as described in the conventional method. Using the above recrystallisation procedure, the pure products 2(a-i) were isolated. 4'-(1,7'-dimethyl-2'-propyl-1H-[2,5']bibenzoimidazolyl-3'ylmethyl)-biphenyl-2-carbonitrile (2a) It was obtained from bibenzoimidazole 1 (1g 3.29mmol) and 4 -bromomethyl-biphenyl-2-carbonitrile (1.07g 3.95 mmol) with N,N- Dimethylformamide as solvent. -1 IR max (KBr cm ): 3080, 2929, 2210, 1612, 1410, 1314, 1290. 1

H NMR (CDCl3) : 0.98 (t, 3H, -CH3), 1.72 (q, 2H, CH2), 2.66 (s, 3H, -CH3), 2.9 (t, 2H, -CH2), 3.79 (s, 3H, -NCH3) 5.66 (s, 2H, -CH2), 7.15-8.00 (m, 14H, ArH). Anal. Calcd. For C33H29N5.C (79.97), H (5.90) N (14.13). Found C (79.95), H (5.89) N (14.10). 3'-(2-bromo-4,5-dimethoxy-benzyl)-1,7'-dimethyl-2'-propyl1H,3'H-[2,5'] bibenzoimidazolyl (2b) It was obtained from bibenzoimidazole 1 (1g 3.29mmol) and 1-Bromo-2-bromomethyl-4,5-dimethoxy-benzene (1.22g 3.95 mmol) with N,N- Dimethylformamide as solvent. -1 IR max (KBr cm ): 3062, 2991, 2920, 1413, 1200, 1150, 812. 1

H NMR (CDCl3) : 0.98 (t, 3H, -CH3), 1.72 (q, 2H, CH2), 2.52 (s, 3H, -CH3), 2.73 (t, 2H, -CH2), 3.48 (s, 3H, -NCH3), 3.59 (s, 3H, -OCH3), 3.76 (s, 3H, -OCH3), 5.55 ( s, 2H, -CH2), 6.44 (s, 1H, Ar-H), 7.2-7.78 (m, 7H, Ar-H).

Nanjunda Swamy et al.

Anal. Calcd. For C28H29N4BrO2.C(63.04), H(5.48), N(10.50). Found C(63.01), H(5.44), N (10.54). 1,7'-dimethyl-3'-(4-nitro-benzyl)-2'-propyl-1H,3'H-[2,5'] bibenzoimidazolyl 2c It was obtained from bibenzoimidazole 1 (1g 3.29mmol) and 1-bromomethyl-4-nitro-benzene 216 (0.853g 3.95 mmol) with N,N- Dimethylformamide as solvent. IR 1212.

-1

max (KBr cm ): 3019, 2965, 2920, 1615, 1410,

1

H NMR (CDCl3) : 0.96 (t, 3H, -CH3), 1.71 (m, 2H, CH2), 2.69 (s, 3H, Ar-CH3), 2.80 (t, 2H, -CH2), 3.88 (s, 3H, N-CH3), 5.71 (s, 2H, -CH2), 7.16-7.85 (m, 8H, Ar-H), 8.12 (dd, 2H, Ar-H). Anal. Calcd. For C26H25N5O2. C(71.05), H(5.73), N(15.93). Found C (71.10), H(5.71), N(15.91). 2-[2-(1,7'-dimethyl-2'-propyl-1H-[2,5']bibenzoimidazolyl3'-yl)-ethyl]-isoindole-1,3-dione (2d) It was obtained from bibenzoimidazole 1 (1g 3.29mmol) and 2-(2-chloro-ethyl)-isoindole-1,3-dione (0.825g 3.95 mmol) with N,N- Dimethylformamide as solvent. IR

-1

max (KBrcm ): 3022, 2965, 1695, 1410, 1315.

1

H NMR (CDCl3) : 0.99 (t, 3H, -CH3), 1.69 (m, 2H, CH2), 2.66 (s, 3H, Ar-H), 2.82 (t, 2H, -CH2), 3.52 (s, 3H, -NCH3), 4.29 (t, 2H, -CH2), 4.41 (t, 2H, -CH2), 7.19-8.15(m, 10H, Ar-H). Anal. Calcd. For C29H27N5O2. C(72.94), H(5.70), N(14.66). Found C(72.92), H(5.74), N (14.70). 1,7'-dimethyl-3'-(6-methyl-benzo[1,3]dioxol-5-ylmethyl)-2'propyl-1H,3'H-2,5'] bibenzoimidazolyl (2e) It was obtained from bibenzoimidazole 1 (1g 3.29mmol) and 5-chloromethyl-6-methyl-benzo[1,3]dioxole 184 (0.726g 3.95 mmol) with N,N- Dimethylformamide as solvent. IR 1220.

-1

max (KBr cm ): 3029, 2991, 1625, 1400, 1310,

1

H NMR (CDCl3) : 0.99 (t, 3H, -CH3), 1.82 (q, 2H, CH2), 2.25 (s, 3H, Ar-CH3), 2.69 (s, 3H, Ar-CH3), 3.87 (s, 3H, -N-CH3), 5.45 (s, 2H, -CH2), 5.87 (s, 2H, -CH2), 7.197.80 (m, 9H, Ar-H). Anal. Calcd. For C28H28N4O2 C(74.31), N(12.38). Found: C(74.32), H(6.26), N( 12.42).

H(6.24),

1-(4-chloro-phenyl)-2-(1,7'-dimethyl-2'-propyl-1H[2,5']bibenzoimida-zolyl-3'-yl)ethanone (2f) It was obtained from bibenzoimidazole 1 (1g 3.29mmol) and 2-bromo-1-(4-chloro-phenyl)ethanone (0.92g 3.95 mmol) with N,N- Dimethylformamide as solvent. IR

-1

max (KBr cm ): 3025, 2990, 1715, 1415, 1210

1

H NMR (CDCl3) : 0.98 (t, 3H, -CH3), 1.75 (m, 2H, CH2), 2.71 (s, 3H, Ar-CH3), 2.82 (t, 2H, -CH2), 3.85 (s, 3H, N-CH3), 5.92 (s, 2H, -CH2), 7.10-7.92 (m, 10H, Ar-H). Anal. Calcd. For C27H25N4ClO. C(70.97), H(5.51), N(12.26). Found C(70.99), H(5.49), N( 12.31).

Antimicrobial Studies

Letters in Drug Design & Discovery, 2009, Vol. 6, No. 5

1,7'-dimethyl-2'-propyl-3'-[2'-(2-trityl-2H-tetrazol-1-yl)biphenyl-4-ylmethyl]-1H,3' H-[2,5']bibenzoimidazolyl (2g) It was obtained from bibenzoimidazole 1 (1g 3.29mmol) and 5-(4'-bromomethyl-biphenyl-2-yl)-1-trityl-1H-tetrazole (2.21g 3.95 mmol) with N,N- Dimethylformamide as solvent. IR 1210.

-1

max (KBrcm ): 3040, 2967, 1615, 1400, 1308,

1

H NMR (CDCl3) : 0.98 (t, 3H, -CH3), 1.83 (q, 2H, CH2), 2.66 (s, 3H, -CH3), 2.89 (t, 2H, -CH2), 3.71 (s, 3H, -NCH3), 5.56 (s, 3H, -CH2), 6.79-8.05 (m, 29H, Ar-H). Anal. Calcd. For C51H45N9. C(78.13) H(5.79), N(16.08). Found C(78.10), H(5.81), N( 16.12). 4'-(1,7'-dimethyl-2'-propyl-1H-[2,5']bibenzoimidazolyl-3'ylmethyl)-biphenyl-2-carboxylic acid methyl ester (2h) It was obtained from bibenzoimidazole 1 (1g 3.29mmol) and 4'-bromomethyl-biphenyl-2-carboxylic acid methyl ester (1.2g 3.95 mmol) with N,N- Dimethylformamide as solvent. -1 IR max (KBr cm ): 3020, 2961, 2916, 1740, 1413, 1310, 1200. 1

H NMR (CDCl3) : 1.02 (t, 3H, -CH3), 1.79 (m, 2H, CH2), 2.78 (s, 3H, -CH3), 2.95 (m, 2H, -CH2), 3.52 (s, 3H, N-CH3), 3.93 (s, 3H, -OCH3), 5.81 (s, 2H, -CH2), 7.1-8.0 (m, 14H, Ar-H). Anal. Calcd. For C34H32N4O2. C(77.25), H(6.10), N(10.60). Found C(77.27), H(6.12), N( 10.64). 4'-(1,7'-dimethyl-2'-propyl-1H-[2,5']bibenzoimidazolyl3'-ylmethyl)-biphenyl-2-carboxylic acid tert-butyl ester (2i) It was obtained from bibenzoimidazole 1 (1g 3.29mmol) and 4'-bromomethyl-biphenyl-2-carboxylic acid tert-butyl ester (1.37g 3.95 mmol) with N,N- Dimethylformamide as solvent. -1 IR max (KBr cm ): 3011, 2929, 1739, 1619, 1400, 1159, 1311. 1

H NMR (CDCl3) : 0.96 (s, 9H, -C(CH3)3), 1.28 (t, 3H, CH3), 1.79 (m, 2H, -CH2), 2.65 (s, 3H, -CH3), 2.96 (t, 2H, CH2), 3.87 (s, 3H, -N-CH3), 5.63 (s, 2H, -CH2), 7.12-7.85 (m, 14H, Ar-H). Anal. Calcd. For C37H38N4O2. C(77.87), H(6.71), N(9.82). Found C(77.84), H(6.75), N( 9.84).

with DMSO were used as negative controls. The bacteria were grown in LB broth overnight, centrifuged at 5,000 rpm for 5mins, pellet was suspended in double distilled water and was used to inoculate the plates. The filamentous fungal inoculum was prepared with the spores derived from 5 to 15 days culture on PDA medium. The mycelia were covered with 10ml of distilled water and the conidia were scraped using a sterile pipette. The spores were recovered after filtration on sterile absorbent cotton and were resuspended in sterile distilled water. The cell density of each inoculum was adjusted with hemocytometer in order to obtain a final concentration of approximately 104 CFU/ml and 106 spores/ml for the bacteria and filamentous fungi respectively. Nystatin (Himedia) was used as a positive control for fungi and streptomycin and tetracycline for bacteria. Each disk contained 10 g of standard drugs and 25 g synthesized compounds. Plates were first kept at 4°C for at least 2 hours to allow the diffusion of chemicals and then incubated at 28°C. Inhibition zones were measured after 24 hours of incubation for bacteria and after 48 hours of incubation for fungi. CONCLUSION In summary, we have synthesized novel bibenzoimidazolyl derivatives 2(a-i) under both conventional and microwave irradiation technique (solution phase). It is thus concluded that under microwave heating, the products 2(a-i) were obtained in good yield in the range of 80-85% at lesser reaction time. From antimicrobial activity data, it seems that nature of the substituent on the bibenzimidazole ring is critical. The data reveals that, the compounds 2a, 2c, 2e, 2f and 2h may serve as a new class of antimicrobials and found to be non-strain dependent. Further, the research on modification of the title compounds to understand the structure activity relationship and the mechanism of inhibition is currently under progress. ACKNOWLEDGEMENTS The authors are grateful to CSIR, UGC and DST, Govt. of India for financial support under the projects vide No 01(1904)/03/EMR-I, UGC-SAP (Phase I) DRS Programme DV4/375/2004-05 and SP/I2/FOO/93. We thank NMR Research Center, IISC, Bangalore for the NMR spectral analysis. One of the author thanks CSIR, Govt of India for the award of CSIR-Senior Research Fellowship.

BIOLOGY

REFERENCES

Materials and Methods

[1]

Bacteria and fungal species used were obtained from the Department of Studies in Biotechnology, University of Mysore, India, namely, Bacillus substilis, Escherichia coli, Pseudomonas fluorescens, Xanthomonas campestris pvs, Xanthomonas oryzae, Aspergillus niger, Aspergillus flavus, Fusarium oxysporum, Trichoderma species and Fusarium monaliforme. The bacterial strains were maintained on LB agar medium and the filamentous fungi were maintained on potato dextrose agar (PDA) medium at 28 C. The disk diffusion method [25] was used to determine antibacterial and antifungal activity of synthesized compounds. Paper discs

385

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