SYNTHESIS, CHARACTERIZATION OF MANNICH BASE TRANSITION METAL COMPLEXES: DNA BINDING AND ANTI BACTERIAL STUDIES
Abstract
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 Objective: Succinimide (pyrolidine 2,5-dione) is a synthetically versatile substrate used for the synthesis of heterocyclic compounds and as a raw material for drug synthesis. Derivatives of succinimide are of important biological and pharmaceutical interest.
Methods: The novel mannich base 1-((2,5-dioxopyrrolidin-1-yl)(4-methoxyphenyl)methyl)thiourea succinimide, methoxy benzaldehyde and thiourea (SMBTU) has been synthesized in good yield by condensation of equimolar quantities of SMBTU. manganese (II), cobalt (II), nickel (II) and copper (II) complexes of the above ligand have also been synthesized.
Results: Structures of newly synthesized compounds were confirmed by elemental analysis, infrared, ultraviolet-visible and nuclear magnetic resonance. All the complexes adopt octahedral geometry around the metal ions. All the newly synthesized compounds were screened for their anti-microbial activity against Escherichia coli and Bacillus subtilis bacteria by minimal inhibitory concentration technique. The binding of the cobalt chloride complex of the ligand with calf thymus DNA has been investigated using absorption spectroscopy, fluorescence spectroscopy and viscosity measurements.
Conclusion: All the complexes exhibit octahedral geometry. The ligand and its metal complexes have shown significant antibacterial activity. The Co (II) metal complex showed efficient DNA binding ability and the binding constant value is consistent with other typical intercalators.
Keywords: Mannich base, Metal complexes, Anti-bacterial, DNA binding, Fluorescence and Viscosity measurements
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Tramontini M. Advances in the chemistry of Mannich bases. Synthesis 1973;1993(12):703-5.
Tramontini M, Angiolini L. Further advances in the chemistry of Mannich bases. Tetrahedron 1990;46:1791.
Tramontini M, Angiolini L. Mannich Bases: Chemistry and Uses. Boca Raton: RC Press; 1994.
Joshi S, Khosla N, Tiwari P. In vitro study of some medicinally important Mannich bases derived from antitubercular agent. Bioorg Med Chem 2004;12(3):571-6.
Joshi S, Manikpuri AD, Khare D. Synthetic spectroscopic and antibacterial studies of Mannich bases of 2-chloro 4-nitro benzamide. J Indian Chem Soc 2008;85:1-5.
Joshi S, Khosla N, Khare D, Tiwari P. Synthesis and antibacterial screening of novel sulfonamide Mannich bases. Acta Pharm 2002;52(3):197-206.
Raman N, Ravichandran S. Synthesis and characterrization of a new schiff base and its metal complexes derived from the Mannich base N-(1-Piperidino benzyl) acetamide. Synth React Inorg Met Org Nano-Metal Chem 2005;35(6):439.
Reshetova K, Ustynyuk YA. Binuclear and polynuclear transition metal complexes with macrocyclic ligands. Russ Chem Bull 2004;53:335.
Zoupy A, Petit A, Hamelin F, Mathe D. New solvent free organic synthesis using focused microwaves. Synthesis 1998;1998(9):1213.
Gangadasu B, Narender P, Raju BC, Rao VJ. Calcium chloride catalyzed three component one pot condensation reactions. An efficient synthesis of 3,4-di hydro pyrimidin 2(1H)-ones. Indian J Chem 2006;45B:1259.
Pelczar MJ, Chan EC, Krieg NR. Microbiology. 5th ed. New York: McGraw-Hill Ltd.; 1998.
Scozzafava A, Menabuoni L, Mincione F, Mincione G, Supuran CT. Carbonic anhydrase inhibitors: Synthesis of sulfonamides incorporating dtpa tails and of their zinc complexes with powerful topical antiglaucoma properties. Bioorg Med Chem Lett 2001;11:575-82.
Walsh C. Enabling the chemistry of life. Nature 2001;409(6817):226 31.
Malhotra E, Kaushik NK, Malhotra HS. Synthesis and studies of ionic chelates of hafnocene with guanine. Indian J Chem 2006;45(2):370-6.
Chandra S, Shukla D, Gupta LK. Synthesis and spectroscopic studies of Co(II), Ni(II) and Cu(II) complexes with N donor (N4) macrocyclic ligand (DSLF). J Indian Chem Soc 2008;85:800-6.
Pathak P, Jolly VS, Sharma KP. Synthesis and Biological activities of some new substituted aryl azo Schiff bases. Orient J Chem 2000;16(1):161-2.
Samadhiya S, Halve A. Synthetic utility of Schiff bases as potential herbicidal agents, Orient J Chem 2001;17(1):119-22.
Bernhardt PV, Lawrance GA. Cobalt. In: McCleverty JA, Meyer TJ, editors. Comprehensive Coordination Chemistry. IInd ed., Vol. 6. Oxford: Elsevier; 2003. p. 1-45.
Dwyer FP, Gyarfas EC, Rogers WP, Koch JH. Biological activity of complexions. Nature 1952;170:190-1.
Hall MD, Failes TW, Yamamoto N, Hambley TW. Bioreductive activation and drug chaperoning in cobalt pharmaceuticals. Dalton Trans 2007;(36):3983-90.
Lopez-Sandoval H, Londono-Lemos ME, Garza-Velasco R, Poblano-Melendez I, Granada-Macias P, Gracia-Mora I, et al. Synthesis, structure and biological activities of cobalt(II) and zinc(II) coordination compounds with 2-benzimidazole derivatives. J Inorg Biochem 2008;102:1267-76.
Ott I, Abraham A, Schumacher P, Shorafa H, Gastl G, Gust R, et al. Synergistic and additive antiproliferative effects on human leukemia cell lines induced by combining acetylenehexacarbonyldicobalt complexes with the tyrosine kinase inhibitor imatinib. J Inorg Biochem 2006;100:1903-6.
Ott I, Schmidt K, Kircher B, Schumacher P, Wiglenda T, Gust R. Antitumour - Active cobalt-alkyne complexes derived from acetylsalicyclic acid; studies on the mode of drug action. J Med Chem 2005;48:622-9.
Miodragovic DU, Bogdanovic GA, Miodragovic ZM, Radulovic MD, Novakovic SB, Kaludjerovic GN, et al. Interesting coordination abilities of antiulcer drug famotidine and antimicrobial activity of drug and its cobalt(II) complex. J Inorg Biochem 2006;100:1568-74.
Nomiya K, Yoshizawa A, Tsukagoshi K, Kasuga NC, Hirakawa S, Watanabe JJ. Synthesis and structural characterization of silver(I), aluminium(III) and cobalt(II) complexes with 4-isopropyltropolone (hinokitiol) showing noteworthy biological activities. Action of silver(I)-oxygen bonding complexes on the antimicrobial activities. Inorg Biochem 2004;98:46-60.
Lv J, Liu T, Cai S, Wang X, Liu L, Wang Y. Synthesis, structure and biological activity of cobalt(II) and copper(II) complexes of valine-derived Schiff bases. J Inorg Biochem 2006;100:1888-96.
Carlin RL. Stereochemistry of Cobalt(II) Complexes in Transition. Metal Chemistry. New York: Marcel Decker; 1965.
Lever AB. Inorganic Electronic Spectroscopy. Amsterdam: Elsevier; 1968.
Drago RS. Physical Methods in Inorganic Chemistry. New Delhi: Affiliated East West Press; 1978.
Khalaji AD. Mononuclear copper(I) complex [Cu (ca2en) (PPh3) (CN)]: Synthesis and characterization. Der Chem Sinica 2011;2(6):7 11.
Lever AB. Inorganic Electronic Spectroscopy. New York: Elsevier; 1968.
Karpenko AS, Shibinskaya MO, Zholobak NM, Olevinskaya ZM, Lyakhov SA, Litvinova LA, et al. Synthesis, DNA binding and intferon-inducing properties of isatin and benzo isatin hydrazones. Pharm Chem J 2006;40:595.
Reddy V, Patil N, Reddy T, Angadi SD. Synthesis and characterization of Cu (II), Co(II), Ni(II) complexes with Schiff bases derived from 3-(4-chloro phenoxy methyl)-4-amino 5mercapto-1,2,4-triazole. Orient J Chem 2008;24(1):201-6.
Agarwal RC, Chandrasekar V. Synthesis and structural studies of some diamine complexes of cobalt (II) and nickel (II) amine and dihydroxy benzoates. J Inorg Nucl Chem 1979;41:1057-61.
Kostava I. Lanthanides and anticancer agents. Curr Med Chem Anticancer Agents 2005;5(6):591-602.
Wolfe A, Shimer GH, Meehan T. Polycyclic aromatic hydrocarbons physically intercalate into duplex regions of denatured DNA. Biochemistry 1987;26:6392-6.
Baguely BC, Le Bert M. Quenching of DNA-ethidium fluorescence by amsacrine and other antitumor agents: A possible electron transfer effect. Biochemistry 1984;23:937-43.
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