SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL STUDY OF MANNICH BASES AND THEIR COPPER (II) COMPLEXES
Keywords:
Mannich base metal complexes, Thiophene-2-carbaldehyde, Anticancer activity of metal complexes and ESRAbstract
Objective: The present study is focused on the synthesis of novel Mannich bases and their metal complexes, and to characterize them by physical, chemical and biological methods. Mannich bases, 2-(piperazin-1-yl(thiophen-2-yl)methyl)hydrazinecarboxamide (PTMHC), 2-(piperazin-1-yl(thiophen-2-yl)methyl)hydrazinecarbothioamide (PTMHCT), and 2-((4-methylpiperazin-1-yl)(thiophen-2-yl)methyl)hydrazinecarboxamide (MPTMHC) and 2-((4-methylpiperazin-1-yl)(thiophen-2-yl)methyl)hydrazinecarbothioamide (MPTMHCT), were prepared by Mannich condensation method.
Methods: The compounds and complexes were prepared by known literature methods. Characterizations were carried out through physical methods such as elemental analyses, melting point and TLC. IR, 1H NMR, [13]C NMR and Mass spectral studies were carried out to characterize the ligands. The methods like EPR, magnetic susceptibility measurements, conductance measurements and thermal analysis were carried out for complexes besides the UV-Vis and IR spectral studies. Anti-cancer activity of synthesized ligands was performed using human lung and colon cancer cell lines.
Results: Eight compounds have been prepared and characterized. Four among the eight compounds were used as ligands for the preparation of metal complexes. The results of physical and chemical methods show all the complexes act as bidentate ligands. The coordination with the metal ion takes place through N, S and O atoms. The results of molar conductivity and magnetic susceptibility measurements reveal the electrolytic and non-electrolytic nature of the metal complexes. EPR and TG-DTA studies also support the other spectral data.
Conclusions: Copper (II) complexes of PTMHC, PTMHCT, MPTMHC, and MPTMHCT were prepared and their structures were determined. The anti-cancer activity of the synthesized ligands and their complexes was evaluated. The synthesized novel ligands of Mannich bases can serve as a potential anti-cancer agent.
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Oyaizu M. Studies on products of browning reactions, antioxidative activities of products. Nutr Jpn J 1986;44:307–15.
Vishnuvardhanaraj G, et al. Synthesis, characterization and biological activities of cinnamaldehyde’s mannich bases. Int J Pharm Pharm Sci 2013;5:821-5.
Nithinchandra, et al. Regioselective reaction, Synthesis, characterization and pharmacological activity of some new Mannich and Schiff bases containing sydnone. Eur J Med Chem 2012;54:597-604.
Jennifer M, Andrews. Determination of minimum inhibitory concentrations. J Antimicrob Chemother 2001;48:5-16.
Report of the working party on antibiotic sensitivity testing of the british society of antimicrobial chemotherapy. A guide to sensitivity testing. J Antimicrob Chemother 1991;27:1-50.
Winstanley T, Edwards C, Limb D, Megson K, Spencer RJ. Evaluation of a surfactant, Dispersol LN, as an anti-swarming agent in agar dilution susceptibility testing. J Antimicrob Chemother 1994;33:353.
NCCLS. Quality assurance for commercially prepared microbiological culture media. Approved Standard M22-A 1990;10:14.
Branson E. Clinical relevance of minimum inhibitory concentration. Aquaculture 2001;196:289-96.
Christfilogiannis P. Current inoculation method in MIC determination. Aquaculture 2001;196:297-302.
Raman N, Esther S, Thangaraja CJ. Chem Sci 2004;116:209-13.
Abdul Jameel A, Syed Ali Padusha M. Indian J Heterocyclic Chem 2006;16:197.
Abdul Jameel A, Syed Ali Padusha M. Pelagia research library. Chem Sin 2012;3:860-3.
Mannich C, Krosche W. The Mannich Reaction revisited. Arch Pharm 1912;250:647.
Henry H, Etery SC, Papageovgiu G, Wilkins KF. Tetrahedron Lett 1998;29:2997.
Ravichandran V, et al. Synthesis and antimicrobial activity of Mannich bases of isatin and its derivatives with 2-(2,6-dichlorophenyl)amino]phenylaceticacid. Arkivoc News Lett 2007;14:51–7.
Tamilvendan D, et al. Syntheses, spectral, crystallographic, antimicrobial, and antioxidant studies of few Mannich bases. Med Chem Res 2011;19:617-716.
Pandeya SN, et al. Synthesis, antibacterial, antifungal and anti-HIV activities of norfloxacin Mannich bases. Eur J Med Chem 2000;35:249–65.
Kwiatkowski W, Karolak-Wojciehowska J. Structure of an anticonvulsant N-methyl-m-bromophenylsuccinimide. Acta Cryst 1992;48:206–8.
Kobayashi S, Hamada T, Manabe K. The catalytic asymmetric Mannich-type reactions in aqueous media. J Am Chem Soc 2002;124:5640-41.
Josephsohn NS, Snapper ML, Hoveyda AH. Ag-catalyzed asymmetric Mannich reactions of enol ethers with aryl, alkyl, alkenyl, and alkynyl imines. J Am Chem Soc 2004;126:3734-5.
Lou S, Taoka BM, Ting A, Schaus SE. Asymmetric Mannich reactions of-keto esters with acyl imines catalyzed by cinchona alkaloids. J Am Chem Soc 2005;127:11256-7.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Immunol J Methods 1983;65:55-63.
Hassan AA, Mourad AE, El-Shaieb KM, Abou-Zeid AHJ. Heterocycl Chem 2006;43:471.
Mannich C, Krosche W. The Mannich Reaction. Arch Pharm 1912;250:647.