Microwave Assisted Synthesis, Spectral and Antimicrobial Evaluation of Hydrazones and Their Metal Complexes

Home , Hydrazone

Devendra Kumar et al. / Journal of Pharmacy Research 2012,5(2),830-834 Research Article Available online through ISSN: 0974-6943 http://jprsolutions.info Microwave assisted synthesis, spectral and antimicrobial evaluation of hydrazones and their metal complexes

Devendra Kumar ,Shivani Singh,Neelam,Rubeena Akhtar Department of Chemistry, Institute of Basic Sciences,Dr. B. R. Ambedkar University, Khandari Campus, Agra-282002 Received on:19-12-2011; Revised on: 07-01-2012; Accepted on:28-01-2012

ABSTRACT Six new metal complexes of Co (II), Ni (II) and Cu (II) with bis-(furfuryl) adipic acid dihydrazone (FADH) and bis- (2-acetyl thiophene) adipic acid dihydrazone (2-ATADH) have been synthesized under microwave irradiation. The Microwave irradiation method was found remarkably successful and gave higher yield at less reaction time. All the synthesized compounds have been characterized by running their TLC for single spot, repeated melting point determinations, elemental analyses, IR, 1H-NMR and electronic spectral studies. The elemental analyses and spectral analysis results revealed their Metal: Ligand (1:1) stoichiometry. All the synthesized compounds have been screened in vitro for their antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa and also for their antifungal activity against Aspergillus niger and Candida albicans.

Key words: Synthesis, Microwave irradiation, Spectral, Antibacterial, Antifungal.

INTRODUCTION Over the last few years, there has been growing interest in the synthesis of Synthesis of diethyl adipate: 14.6 g (0.1M) adipic acid was dissolved in organic compounds under green or sustainable chemistry such as micro- 20 ml absolute alcohol. To this solution, 3ml conc. H2SO4 was added. The wave irradiation because of increasing environmental consciousness. The reaction mixture was irradiated in a microwave at 400W for 4 min and feasibility of microwave assisted synthesis has been demonstrated in vari- transferred to a separating funnel containing 20 ml of distilled water and ous transformations like condensation [1], cycloaddition [2], alkylation [3] and shaken well. The upper pale yellow layer was separated out and treated in many other chemical reactions. The use of microwave irradiation has with excess of saturated solution of sodium bicarbonate to remove unreacted become an established tool in organic synthesis for achieving better selec- acid. It was distilled under reduced pressure to get the desired product. tivity, rate enhancement and reduction of thermal degradation byproducts [4]. Microwave Assisted Synthesis is rapidly becoming the method of choice Synthesis of adipic acid dihydrazide (AADH): 10.02 g (0.05M) diethyl in modern synthesis and discovery in chemistry laboratories. Microwave- adipate was dissolved in 25 ml absolute alcohol in a round bottom flask and assisted synthesis improves both throughput and turn-around time for chem- 4.95 ml (0.1M) hydrazine hydrate, dissolved in 15 ml absolute alcohol, was ists by offering the benefits of drastically reduced reaction times, increased mixed to it. This reaction mixture was irradiated in microwave oven at an yields, and purer products. In this type of synthesis we apply microwave emitted power of 400W for 6 min. The contents of the flask were cooled in radiation to carried out the chemical reactions. Microwave mediated reac- a freezing mixture. A white shiny product was obtained. It was filtered tion have emerged as a powerful technique to promote a variety of chemical washed with alcohol followed by ether and dried in a vacuum desiccator reactions. The microwave irradiation is used for carrying out chemical trans- over anhydrous CaCl . formation which is pollution free and eco-friendly. 2 Synthesis of dihydrazones: 0.348 g (0.002 M) adipic acid dihydrazide Hydrazones having azomethine linkage (>C=N-N) are well known for their (AADH) was dissolved in 15 ml of 30 % acetic acid. To this solution, wide spectrum biological applications such as anti-viral [5], anti-tuberculosis (0.004 M) of 0.33 ml furfuraldehyde for the synthesis of bis-(furfuryl) [6], anti-tumor [7], cardiovascular [8], antiplatelet [9], anti-convulsant [10], anti- adipic acid dihydrazone (FADH)/0.432 ml 2-acetyl thiophene for the syn- malarial [11], anti-depressant, pharmacological [12] activity. It has been ob- thesis of bis-(2-acetyl thiophene) adipic acid dihydrazone (2-ATADH), served that the biological activity[13] of hydrazones increases on complex- dissolved in 15 ml absolute alcohol was added with constant shaking. The ation with transition metal ions. A number of metal complexes of hydrazones resulting solutions were irradiated in a microwave oven at 360W for 4 min have been reported as tuberculositic [14], antitumor [15], antibacterial, antifun- and 6 min respectively. Coloured solid products were obtained which were gal [15] agents. These facts prompted us to synthesise some new hydrazones filtered, washed with alcohol followed by ether and then recrystallized and their metal complexes by adopting green chemistry approach. from a mixture of (1:1) DMF and alcohol. Finally, products were dried in a vacuum desiccator over anhydrous CaCl MATERIALS AND METHODS 2. The synthesis were carried out in a domestic microwave oven LG model Synthesis of Co (II), Ni (II), Cu (II) metal complexes of dihydrazones: MS-1927C. Melting points were taken in open capillaries and are uncor- 25 ml ethanolic solution (0.005M) of 0.302 g bis-(furfuryl) adipic acid rected. All the chemicals used were of AR grade and solvents were purified dihydrazone/ 0.432 ml 2-acetyl thiophene dihydrazone was mixed to 10 ml by suitable methods. aqueous solution (0.005M) of 0.124 g cobalt acetate tetrahydrate / 0.124 g nickel acetate tetrahydrate/ 0.099 gm copper acetate monohydrate sepa- rately in the round bottom flasks. These mixtures were irradiated at 450- *Corresponding author. 500 W in a microwave oven for 5- 7 min. On cooling the solutions, coloured Devendra Kumar precipitates were obtained which were filtered, washed with water fol- Department of Chemistry, lowed by alcohol. Finally, the products were dried in a vacuum desiccator Institute of Basic Sciences, over anhydrous CaCl . Dr. B. R. Ambedkar University, 2 Khandari Campus, Agra-282002 Antimicrobial activity Uttar Pradesh, India The antimicrobial activities were determined using disc diffusion method [17]

Journal of Pharmacy Research Vol.5 Issue 2.February 2012 830-834 Devendra Kumar et al. / Journal of Pharmacy Research 2012,5(2),830-834 by measuring the zone of inhibition [18] in mm. All synthesized compounds The electronic spectrum of Ni(II) complexes exhibited three bands in the -1 3 were screened in vitro for their antibacterial activity against two bacteria region 12981-12624,14910-14335 and 24306-22444 cm assigned to A2g 2 3 3 3 3 (Staphylococcus aureus and Pseudomonas aeruginosa) at different concen- g T2g, A2gg T1g(F) and A2gg T1g (P) respectively which suggested trations of 50, 25,12.5,6.25mg/ml. The bacteria were subcultured in Mueller the octahedral geometry[19]. Hinton Agar medium. Antifungal activity [17] was tested against Candida albicans and Aspergillus niger at different concentration of 50, The electronic spectra of Cu (II) complex exhibited three bands in the 25,12.5,6.25mg/ml. The fungi were subcultured in Saboured’s Dextrose Agar regions 13105-12980, 16545-16225 and 25318-24340 cm-1 corresponding 2 2 2 2 medium. Ciprofloxin was used as a standard for antibacterial and Fluconazole to the transitions B1g g A1g g B2g and E1g respectively which suggest for anti-fungal screening. The complexes were dissolved in 10% DMSO octahedral geometry [20] for these complexes. Three bands may be due to which was found to be biologically inactive. The plates were incubated for John Teller Effect. 24 h at 37 oC for bacteria and 96 h at 28 oC for fungi. Each experiment was done in triplicate and the average mean inhibition zone have been reported. On the basis of IR, 1H-NMR and electronic spectral data it seems reason- The obtained results of zone of Inhibition in terms of mean inhibition zone able to assume the M (II) complexes have the following structure (Fig.1 & and graphical representation of microbial studies for the synthesized com- 2). plexes have been presented in Table.2 -10 respectively.

RESULTS AND DISCUSSION Elemental analyses were carried out on Carlo Earba 1108 elemental ana- lyzer (Results have been presented in Table 1). Infrared spectra were recorded on Perkin Elmer spectrophotometer using KBr pellets in the range 4000-400 cm-1. 1H-NMR spectra were recorded on a Bruker DRX- spec- trometer at 300 MHz using TMS as internal standard and DMSO-d6 and CDCl3 as solvents. Chemical shifts (d) were expressed in ppm downfield from internal standard TMS. Electronic spectra of metal complexes were recorded in DMSO solvent on Shimadzu UV 1800 Spectrophotometer.

The IR and 1H-NMR spectral data:

Adipic acid dihydrazide -1 Fig.1: Metal complexes of bis-( furfuryl) adipic acid dihydrazone IR (KBr, umax in cm ): 3289.3(NH2), 3176.6 (NH), 3020.7 (CH), 1661.4 (CO), 1532.0 (CH bending), 1216.7 (C-N), 1033.6 (N-N). 1H NMR (300

MHz, DMSO, d ppm) 2.500 (2H, s, NH2), 8.908 (1H, s, -CONH), 2.353- 2.307 (2H, t, -CH2CO), 1.193-1.145(2H, m, -CH2). Bis - (furfuryl) adipic acid dihydrazone -1 IR (KBr,umax in cm ): 3177.2(NH), 2936.3(CH), 1665.6 (CO), 1591.2(C=N), 1446.6(Furan ring), 1217.6(C-N), 1020.0(N-N). 1H NMR (300 MHz, DMSO, d ppm) 7.855 (1H,s, -CONH), 2.500-2.184(2H,t, -

CH2CO), 1.602-1.581(2H,t, -CH2), 6.859-6.819(3H,m, furyl ring), 7.768 (1H,s, azomethine proton).

Bis-(2-acetyl thiophene) adipic acid dihydrazone -1 IR (KBr, umax in cm ): 3178.2(-NH), 3020(CH), 1663.3(CO), 1590.0(C=N), 1 1216.6(CN), 1051.8(N-N), 669.9(C-S). H NMR (300 MHz, DMSO, d Fig.2: Metal complexes of bis-(2-acetylthiophene) adipic acid dihydrazone ppm) 7.312(1H,s,-CONH), 2.327-2.232 (2H,t,-CH2CO), 1.772-1.748 (2H,t,-CH2), 1.224 (3H,s,CH3),7.181- 6.984 (3H, m, thiophenyl ring). Co (II), Ni (II), Cu (II) complexes of bis-(furfuryl) adipic acid ANTIMICROBIAL ACTIVITIES dihydrazone The comparison of antimicrobial results of the metal complexes with their -1 respective ligands showed that the maximum zone of inhibition increases in IR (KBr, umax in cm ): 3451.4-3411.3, (mixing of –NH and –OH), 2934.5- 2931.3(CH),1659.5-1657.8 (CO), 1553.1-1549.6 (C=N), 1473.2-1470.9 complexes. Among the metal complexes of FADH, the maximum zone of (Furan ring), 1220.3-1218.7(C-N), 1078.9-1014.3(N-N), 936.1-926.1 (OH inhibition was found 11 mm against Pseudomonas aeruginosa for cobalt deformation), 569.9-557.8, (M-N), 496.3-489.0 (M-O). complex at the concentration 50mg/ml where as against Staphylococcus aureus the maximum zone of inhibition was found 10.3 mm for copper Co(II),Ni (II), Cu (II) complexes of bis-(2-acetylthiophene) adipic acid complex at the concentration 50 mg/ml. dihydrazone -1 In the case of antifungal study, the maximum zone of inhibition equal to IR (KBr, umax in cm ): 3420.2-3401.9, (mixing of –NH and –OH), 3022.4- 3021.1 (C-H), 1634.0-1625.7(C=O),1563.2-1547.6(C=N), 1219.7- 11mm against the fungi Aspergillus niger was exhibited by copper com- 1217.7(C-N), 1052.1-1024.4, (N-N), 929.7-830.6 (OH deformation),694.9- plex whereas against the fungi Candida albicans, the maximum zone was 671.7 (C-S bending), 571.9-555.7(M-N), 537.5-534.2, (M-O), 428.7-403.2 shown by nickel complex was found to be 7.4 mm. However, among the (M-S). metal complexes of ATADH the maximum zone of inhibition was found 9.6 mm against Pseudomonas aeruginosa, 9.0 mm against Staphylococcus Electronic spectral data aureus, 9.0 mm against Aspergillus niger and 10.3 mm against Candida The electronic spectra of Co (II) complexes exhibited three bands in the albicans at the concentration 50mg/ml which was shown by copper com- region 12650-12623,15389-14354 and 19590-18840 cm-1 corresponding to plex. The comparison of antimicrobial results of complexes with standard 4 4 4 4 4 4 antibacterial and antifungal drugs shown that complexes are less active than the transitions T1gg T2g [F], T1gg A2g [F], T1gg T1g [P] respectively which suggested octahedral geometry[19] for these complexes. standards. Journal of Pharmacy Research Vol.5 Issue 2.February 2012 830-834 Devendra Kumar et al. / Journal of Pharmacy Research 2012,5(2),830-834 Table 1: Physical and analytical data of dihydrazide, dihydrazones and their metal complexes.

S.No Name of Compounds Molecular Colour Elemental Analyses% M.P/D.T± 20C Formula Carbon Hydrogen Nitrogen C/(F) C/(F) C/(F)

1 AADH C6H14N4O2 Shiny white 41.34 8.04 32.18 164 (42.26) (9.15) (33.45)

2. FADH C16H18O4N4 Grey 58.18 5.45 16.96 210 (59.57) (6.87) (17.79)

3. 2-ATADH C18H22O2N4S2 Pale Yellow 55.38 5.64 14.35 195 (56.78) (6.77) (15.58)

4. [Co (FADH). 2H2O]Ac2 C20H28N4O10.Co Brown 44.20 5.15 10.31 240 (45.37) (6.43) (11.32)

5. [Ni (FADH). 2H2O]Ac2 C20H28N4O10.Ni Dark Yellow 44.22 5.15 10.31 298 (45.21) (6.66) (11.53)

6. [Cu (FADH).2H2O]Ac2 C20H28N4O10.Cu Dark Bluish 43.83 5.11 10.22 298 (44.97) (6.76) (11.35)

7. [Co (2-ATADH). 2H2O] Ac2 C22H32N4O8S2.Co Dark Pink 43.78 5.30 9.28 242 (44.57) (6.33) (10.45)

8. [Ni (2-ATADH). 2H2O] Ac2 C22H32N4O8S2.Ni Dark Yellow 43.80 5.30 9.29 265 (44.96) (6.42) (8.34)

9. [Cu (2-ATADH). 2H2O]Ac2 C22H32N4O8S2.Cu Bluish 43.45 5.26 9.21 268 (44.56) (6.37) (10.32)

C = Calculated, F = Found, M.P = Melting Point, D.T = Decomposition Temperature Table 2: The mean inhibition radius zone values with standard deviation (in mm) for hy- Table 4: The mean inhibition radius zone values with standard deviation (in mm) for bis-(2- drazide against tested microorganisms. Acetyl thiophene) adipic dihydrazone against tested microorganisms.

Conc. in P. aeruginosa S. aureus A. niger C. albicans Conc. in P. aeruginosa S. aureus A. niger C. albicans mg/ml mg/ml

50.0 8.3±1.527 10.6±1.154 10.0±0.004 8.6±0.577 50.0 6.0±1.000 8.3±0.577 8.6±0.577 8.0±0.577 25.0 7.3±1.154 7.6±1.527 9.6±0.577 7.6±1.154 25.0 7.3±1.527 7.6±0.577 8.6±0.577 6.3±0.577 12.5 7.0±1.000 7.6±1.154 8.0±1.000 7.0±1.000 12.5 6.0±1.732 7.0±1.000 9.0±0.006 6.0±0.007 6.25 4.6±0.577 6.6±1.527 7.0±1.000 5.3±0.577 6.25 5.6±1.154 4.3±0.577 6.3±1.527 7.0±0.008 Sab/Saf 9.0±0.008 11±1.000 10±1.154 10.8±1.154 Sab/Saf 10±1.154 10.0±1.154 11.0±1.000 12.0±1.000

Sab= Standard antibacterial drug Ciprofloxin and Saf= Standard antifungal drug Flucanazole Sab= Standard antibacterial drug Ciprofloxin and Saf= Standard antifungal drug Flucanazole Mean Inhibition Zone . . Table3: The mean inhibition radius zone values with standard deviation (in mm) for bis- (furfural) adipic dihydrazone against tested microorganisms. Table 5: The mean inhibition radius zone values with standard deviation (in mm) for metal Conc. in P. aeruginosa S. aureus A. niger C. albicans complex of Co(II) furfuraldehyde adipic dihydrazone against tested microorganisms. mg/ml Conc. in P. aeruginosa S. aureus A. niger C. albicans 50.0 6.33±1.527 7.6±1.154 10.0±1.000 6.6±1.154 mg/ml 25.0 7.6±1.527 8.6±0.577 7.3±0.577 6.6±0.577 12.5 6.0±1.527 7.3±1.527 9.0±1.000 6.0±1.008 50 11.0±1.000 9.6±0.577 8.0±1.000 7.3±0.577 6.25 5.6±1.527 9.0±0.005 7.3±1.527 6.3±0.577 25 9.6±1.154 8.6±0.577 7.0±1.000 7.0±0.004 S /S 12.0±0.008 10±1.154 15.0±0.007 15.5±1.41 12.5 7.3±1.154 7.3±0.577 7.6±1.154 6.6±0.577 ab af 6.25 5.2±1.527 5.0±1.000 7.3±0.577 5.3±0.577

Sab/Saf 12.0±0.005 11.0±1.000 10.0±1.154 11.0±1.000 Sab= Standard antibacterial drug Ciprofloxin and Saf= Standard antifungal drug Flucanazole

Sab= Standard antibacterial drug Ciprofloxin and Saf= Standard antifungal drug Flucanazole Mean Inhibition Zone

Concentration Journal of Pharmacy Research Vol.5 Issue 2.February 2012 830-834 Devendra Kumar et al. / Journal of Pharmacy Research 2012,5(2),830-834 Table 6: The mean inhibition radius zone values with standard deviation (in mm) for metal Table 9: The mean inhibition radius zone values with standard deviation (in mm) for metal complex of Ni(II) furfuraldehyde adipic dihydrazone against tested microorganisms. complex of Ni(II) Adipic acid dihydrazone against tested microorganisms. Conc. in P. aeruginosa S. aureus A. niger C. albicans mg/ml Conc. in P. aeruginosa S. aureus A. niger C. albicans mg/ml 50.0 9.0±1.000 8.0±1.000 10.3±1.527 7.4±1.154 25.0 6.6±1.154 6.3±0.577 9.0±1.000 6.6±0.577 50.0 9.0±1.732 8.3±1.527 7.6±0.577 7.0±1.732 12.5 6.0±1.000 6.6±1.154 8.6±1.527 6.3±0.577 25.0 7.0±1.732 8.0±1.000 7.6±0.577 6.0±1.000 6.25 6.3±1.525 6.3±0.577 7.6±0.577 5.6±0.577 12.5 6.6±1.527 7.0±1.000 7.0±0.007 6.0±1.000 6.25 4.3±0.577 5.3±1.154 6.6±0.577 6.0±1.000 Sab/Saf 13.0±0.577 11.0±1.000 12.0±1.000 10.0±1.154 Sab/Saf 10.0±1.000 10.0±1.154 9.0±1.000 9.0±1.732

Sab= Standard antibacterial drug Ciprofloxin and Saf= Standard antifungal drug Flucanazole Sab= Standard antibacterial drug Ciprofloxin and Saf= Standard antifungal drug Flucanazole

Table 7: The mean inhibition radius zone values with standard deviation (in mm) for metal complex of Cu(II) furfuraldehyde adipic dihydrazone against tested microorganisms.

Conc. in P. aeruginosa S. aureus A. niger C. albicans Table 10: The mean inhibition radius zone values with standard deviation (in mm) for metal mg/ml complex of Cu(II) Adipic acid dihydrazone against testedmicroorganism.

50.0 8.3±0.577 10.3±0.577 11.0±1.000 6.6±1.527 Conc. in P. aeruginosa S. aureus A. niger C. albicans 25.0 7.6±0.577 9.0±1.000 8.6±0.577 6.3±1.154 mg/ml 12.5 7.3±1.527 9.3±0.577 7.6±0.577 5.3±0.577 6.25 6.6±0.577 8.0±1.732 6.6±0.577 4.6±0.577 50.0 9.6±1.157 9.0±1.000 9.0±1.000 10.3±1.000 S /S 10.0±1.732 10.0±0.008 11.0±1.000 12.0±1.000 ab af 25.0 6.0±1.000 7.3±0.577 8.3±0.577 6.6±1.527 12.5 7.0±0.008 6.6±0.577 8.6±1.154 6.3±0.577 S = Standard antibacterial drug Ciprofloxin and S = Standard antifungal drug Flucanazole ab af 6.25 6.3±1.527 5.3±0.577 7.0±1.732 6.6±0.577

Sab/Saf 10.0±0.006 11.0±1.000 10.0±1.154 10.0±1.732

Sab= Standard antibacterial drug Ciprofloxin and Saf= Standard antifungal drug Flucanazole

Table8: The mean inhibition radius zone values with standard deviation (in mm) for metal complex of Co(II) Adipic acid dihydrazone against tested microorganisms. Conc . in P. aeruginosa S. aureus A. niger C. albicans mg/ml CONCLUSION 50 8.0±1.732 7.0±0.008 8.6±0.577 7.3±1.154 25 5.3±1.527 7.3±1.527 7.6±1.527 6.6±1.154 Structure of all the synthesized compounds were established by melting 12.5 5.6±1.154 7.3±0.577 7.0±1.000 7.3±1.154 point determination, running TLC for single spot, elemental analysis and 6.25 5.6±1.154 6.3±0.577 7.0±1.000 5.0±1.000 by spectral analysis involving IR, 1H-NMR, electronic studies. All the S /S 10.0±1.154 11.0±0.007 10.5±0.577 12.0±0.008 ab af synthesized compounds were evaluated for the above mentioned activities Sab= Standard antibacterial drug Ciprofloxin and S = Standard antifungal drug Flucanazole af and they have exhibited promising activity. It was found that microwave assisted approach is highly efficient procedure. The reaction occurred remarkably fast, under mild condition using domestic microwave oven as the irradiation source. The benefits of this method are environmentally benign, easy work, high yield of products, short reaction time.

ACKNOWLEDGEMENT Authors are thankful to Head, Department of Chemistry, Institute of Basic Sciences for providing necessary facilities for conducting lab work, Sophis- ticated Analytical Instrument Facility (SAIF) a division of CDRI, Lucknow (India) for providing C, H, N analyses and IR, NMR and electronic spectral

Journal of Pharmacy Research Vol.5 Issue 2.February 2012 830-834 Devendra Kumar et al. / Journal of Pharmacy Research 2012,5(2),830-834 analyses results. The antibacterial activity was done in collaboration with Derivatives, Molecules, 12, 2007, 1910-1939. Microbiology Department, School of Life Sciences, Dr. B. R. Ambedkar 11. Khan S, Mullick P, Pandit S, Kaushik D.; Synthesis of Hydrazones University, Agra. derivatives of quinoxalinone and prospective antimicrobial and an- tiinflammatory agents, Acta Poloniae Pharmaceutica-Drug Re- REFERENCES search, 66(2), 2009, 169-172. 1. Jain AK, Gupta PK, Ganesan K, Pande A and Malhotra RC.; Rapid 12. Pervez H, Ahmad M, Yaqub M, Somra MA, Iqbal F, Khan KM.; Solvent free Synthesis of Aromatic Hydrazides under Microwave Synthesis and Biological Evaluation of some Novel Isatins- Derived Irradiation, Defence Science Journal, 57, 2007, 267-270. Hydrazones, Journal of Pharmacy Research, 4(12), 2011, 4355- 2. Soriente A, Spinella A, DeRosa M, Giordano M and Scettri A.; Solvent 4358. free reaction under microwave irradiation: A new procedure for 13. Syed Tajudeen S, Santha Lakshmi S, Kannappan Geetha, Studies on Eu+3- Catalyzed Tetrahedron Lett., 38, 1997, 289-290. antimicrobial activity of some hydrazones and its Copper com- 3. Varma RS.; Solvent-free synthesis of amides from non-enolizable plexes, Journal of Pharmacy Research,3(11), 2010, 2759-2760. esters and amines using microwave irradiation, Green Chemistry, 14. Singh NK, Agarwal N and Aggarwal RC.; Synthesis, Characterization 43, 1999. and antibacterial studies of iron(II), cobalt(II), nickel(II), copper(II) 4. Caddick S.; Microwave-Assisted Organic Reactions, Tetrahedron, 51, and zinc(II) complexes of pyridine-4-carboxaldehyde isonicotinoyl 1995, 10403-10432. hydrazone, Indian J. Chem., 23A, 1984, 1011-1015. 5. Neamati N, Lin Z, Karki RG, Orr A, Cowansage K, Strumberg D, Pais 15. Kumar A, Verma A, Chawla G, Vaishali.; Synthesis anti-inflamma- GCG, Voigt JH, Nicklaus MC, Winslow, HE, Zhao H, Turpin JA, Yi tory and antimicrobial activities of new hydrazone and quinoxaline J, Skalka, AM, Burke TR. Jr and Pommier Y.; Metal dependent derivatives, International J. Chem. Tech. Research, 1(4), 2009,1177- inhibition of HIV-1 integrase, J. Med.Chem., 45, 2002, 5661-5670. 1181. 6. Cavier R and Rapier R, Microwave Assisted Organic Reactions, 16. El-Hamouly W, Moustafa E, Abbas H, Tawfik H.; One-pot synthesis J.Med.Chem. 8(5), 1965, 706-708. of some (1H)- quinoxalin-2-ones, African J. Pure and Applied 7. Salgin-Goksen U, Gokhan-Kelekci N, Goktas O, Koysal Y, Kilic E, Chem., 4(1), 2010, 4320-4560. Isik S, Aktay G and Ozalp M.; 1-Acylthiosemicarbazides, 1,2,4- 17. Nadaraj V, Selvi ST, Mohan S, Thangadurai D.; Microwave-assisted triazole-5(4H)-thiones, 1,3,4-thiadiazoles and hydrazones containing effective synthesis and biological activities of 3-cyano-1- 5-methyl-2-benzoxazolinones:synthesis, analgesic-anti-inflamma- phenylbenzo[g][1,8]naphthyridone and their derivatives, Journal tory and antimicrobial activities, Bioorg. Med. Chem., 15, 2007, of Pharmacy Research,3(12),2010,3129-3131. 5738-5751. 18. Marakkur V, Darshan Raja CG, Sarojinia BK, Sreenivasa S, Jayaramu 8. Uchida K.; 4-Hydroxy-2-nonenal: a product and mediator of oxida- M.; Synthesis, Characterization, evalution of antiproliferative and tive stress, Free Radical Biol. Med., 28(12), 2000, 1685-1696. antimicrobial properties of new pyrazole derivatives, Journal of 9. Ajani O, Craig A, Obafemi O, David A, Akinpelu.; Microwave assisted Pharmacy Research,4(8),2011,2787-2790. synthesis and antimicrobial activity of 2-quinoxalinone- hydrazone 19. Lever ABP.; Inorganic Electronic Spectroscopy, Elsevier, Amsterdam, derivatives, Bioorg Med. Chem., 2010, 214–221. 1968. 10. Rollas S and Kucukguzel SG.; Biological Activities of Hydrazone 20. Lever ABP and Mantovani E.; Inorg. Chem., 10, 1971, 40.

Source of support: Nil, Conflict of interest: None Declared

Journal of Pharmacy Research Vol.5 Issue 2.February 2012 830-834