ABC  Vol.6 No.6 , December 2016
Biological Evaluation of New Schiff Bases: Synthesized from 4-Amino-3,5-dimethyl-1,2,4-triazole, Phenathroline and Bipyridine Dicarboxaldehydes
Abstract: Four new Schiff bases with promising anticancer activity have been synthesized from 4-amino-3,5-dimethyl-1,2,4-triazole and di-pyridyl-aldehydes. Structures have been established by various spectroscopic methods. The compounds were tested in vitro to study their cytotoxicity and anti-oxidative activity in human lung carcinoma (A549), breast carcinoma (BT549), prostate adenocarcinoma (PC3) and mouse preadipocytes (3T3-L1) cells. Compound 1 was found to increase Glutathione (GSH) level slightly in all four cell lines. Compound 4 showed better selectivity and cytotoxicity against both BT549 and A549 cells compared to the anticancer drug tamoxifen. With the exception of compound 4 which reduced GSH levels in A549 and BT549, all other compounds maintained GSH levels in comparison to their respective controls.
Cite this paper: Islam, M. , Karim, M. , Boadi, W. , Falekun, S. and Mirza, A. (2016) Biological Evaluation of New Schiff Bases: Synthesized from 4-Amino-3,5-dimethyl-1,2,4-triazole, Phenathroline and Bipyridine Dicarboxaldehydes. Advances in Biological Chemistry, 6, 180-192. doi: 10.4236/abc.2016.66016.

[1]   American Cancer Society (2015) Global Cancer Facts and Figures. 3rd Edition, American Cancer Society, Atlanta.

[2]   Waghorne, C.L., Corkran, H.M., Hunt-Painter, A.A., Niktab, E., Baty, J.W., Berridge, M.V., Munkacsi, A.B., McConnell, M.J., Timmer, M.S.M. and Stocker, B.L. (2016) N,N-Bis(gly- cityl)amines as Anti-Cancer Drugs. Bioorganic and Medicinal Chemistry, 24, 3932-3939.

[3]   Bala, S., Uppal, G., Kamboj, S., Saini, V. and Prasad, D.N. (2012) Design, Characterization, Computational Studies, and Pharmacological Evaluation of Substituted-N’-[(1E)substituted- phenylmethylidene]benzohydrazide Analogs. Medicinal Chemistry Research, 21, 1-13.

[4]   Wu, H., Jia, F., Kou, F., Liu, B., Yuan, J. and Bai, Y. (2011) A Schiff Base Ligand N-(2-Hydro- xyacetophenone)-3-oxapetane-1,5-diamine and Its Nickel(II) Complex: Synthesis, Crystal Structure, Antioxidation and DNA-Binding Properties. Transition Metal Chemistry, 36, 847- 853.

[5]   Sing, G., Sharma, P., Dadhwal, S., Garg, P., Sharma, S., Mahajan, N. and Rawal, S. (2011) Triazoles—Impinging the Bioactivities. International Journal of Current Pharmaceutical Research, 3, 105-118.

[6]   Singhal, N., Sharma, P.K., Dudhe, R. and Kumar, N. (2011) Recent Advancement of Triazole Derivatives and Their Biological Significance. Journal of Chemical and Pharmaceutical Research, 3, 126-133.

[7]   Tarafder, M.T., Kasbollah, A., Saravan, N., Crouse, K.A., Ali, A.M. and Tin, O.K. (2002) S-Methyldithiocarbazate and Its Schiff Bases: Evaluation of Bondings and Biological Properties. Journal of Biochemistry, Molecular Biology and Biophysics, 6, 85-91.

[8]   Sahu, R., Thakur, D.S. and Kashyap, P. (2002) Schiff Bases: An Overview of its Medicinal Chemistry Potential for New Drug Molecules. International Journal of Pharmaceutical Sciences and Nanotechnology, 5, 1757-1764.

[9]   Vicini, P., Geronikaki, A., Incerti, M., Busonera, B., Poni, G., Kabras, C.A. and Colla, P.L. (2003) Synthesis and Biological Evaluation of Benzo[d]isothiazole, Benzothiazole and Thiazole Schiff Bases. Bioorganic and Medicinal Chemistry, 11, 4785-4789.

[10]   Jaman, Z., Karim, M.R., Dumenyo, K. and Mirza, A.H. (2014) Antibacterial Activities of New Schiff Bases and Intermediate Silyl Compounds Synthesized from 5-Substituted-1,10- phenanthroline-2,9-dialdehyde. Advances in Microbiology, 4, 1140-1153.

[11]   Pignatello, R., Panico, A., Mazzane, P., Pinizzotto, M.R., Garozzo, A. and Fumeri, P.M. (1994) Schiff Bases of N-Hydroxy-n-aminoguanidines as Antiviral, Antibacterial and Anticancer Agents. European Journal of Medicinal Chemistry, 29, 781-785.

[12]   Paudyal, R., Jamaluddin, A., Warren, J.P., Doyle, S.M., Robert, S., Warriner, S.L. and Baker, A. (2014) Trafficking Modulator TENin1 Inhibits Endocytosis, Causes Endomembrane Protein Accumulation at the Pre-Vacuolar Compartment and Impairs Gravitropic Response in Arabidopsis thaliana. Biochemical Journal, 460, 177-185.

[13]   Ma, L., Zhu, M., Wang, Q., Li, Y., Xing, S., Fu, X., Gao, Z. and Dong, Y. (2011) Mononuclear Copper(II) Complexes with 3,5-Substituted-4-salicylidene-amino-3,5-dimethyl-1,2,4- triazole: Synthesis, Structure and Potent Inhibition of Protein Tyrosine Phosphatases. Dalton Transactions, 40, 6532-6540.

[14]   Hu, G., Wang, G. and Duan, N. (2012) Design, Synthesis and Antitumor Activities of Fluoroquinolone C-3 Heterocycles(IV): S-Triazole Schiff-Mannich Bases Derived from Ofloxacin. Acta Pharmaceutica Sinica B, 2, 312-317.

[15]   Jordan, V.C. (1993) A Current View of Tamoxifen for the Treatment and Prevention of Breast Cancer. British Journal of Pharmacology, 110, 507-517.

[16]   Marí, M., Morales, A., Colell, A., García-Ruiz, C. and Fernández-checa, J.C. (2009) Mitochondrial Glutathione, a Key Survival Antioxidant. Antioxidants and Redox Signaling, 11, 2685-2700.

[17]   Cheng, L., Zhang, W. X., Ye, B.H., Lin, J.B. and Chen, X.M. (2007) In Situ Solvothermal Generation of 1,2,4-Triazolates and Related Compounds from Organonitrile and Hydrazine Hydrate: A Mechanism Study. Inorgnic Chemistry, 46, 1135-1143.

[18]   Thiele, S., Malmgaard-Clausen, M., Engel-Andreasen, J., Steen, A., Rummel, P.C., Nielsen, M.C., Gloriam, D.E., Frimurer, T.M., Ulven, T. and Rosenkilde, M.M. (2012) Modulation in Selectivity and Allosteric Properties of Small-Molecule Ligands for CC-Chemokine Receptors. Journal of Medicinal Chemistry, 55, 8164-8177.

[19]   Arifuzzaman, M., Karim, M.R., Siddiquee, T.A., Mirza, A.H. and Ali, M.A. (2013) Synthesis and Characterization of New Schiff Bases Formed by Condensation of 2,9-Phenanthroline- 1,10-dialdehyde with Sulfur-Containing Amines. International Journal of Organic Chemistry, 3, 81-86.

[20]   Gouthaman, S., Periyaraja, S. and Shanmugam, P. (2015) Bipyridine Carbaldehydes as Electrophiles in the Morita-Baylis-Hillman Reaction: Synthesis of Highly Functionalized Bipyridyl Ligands and a Macrocycle. Tetrahedron Letters, 56, 5920-5923.

[21]   Newkome, G.R. and Lee, H.W. (1983) 18[Hexa(2,6)pyridinocoronand-6]: “Sexipyridine”. Journal of American Chemical Society, 105, 5956-5957.

[22]   Razzak, M., Karim, M.R., Hoq, M.R. and Mirza, A.H. (2015) New Schiff Bases from 6,6’-Diformyl-2,2’-bipyridine with Amines Containing O, S, N and F: Synthesis and Characterization. International Journal of Organic Chemistry, 5, 264-270.

[23]   Yang, S.J., Park, N.Y. and Lim, Y. (2014) Anti-Adipogenic Effect of Mulberry Leaf Ethanol Extract in 3T3-L1 Adipocytes. Nutrition Research and Practice, 8, 613-617.

[24]   Mphahlele, M.J., Makhafola, T.J. and Mmonwa, M.M. (2016) In Vitro Cytotoxicity of Novel 2,5,7-Tricarbo-substituted Indoles Derived from 2-Amino-5-bromo-3-iodoacetophenone. Bioorganic and Medicinal Chemistry, 24, 4576-4586.

[25]   Boadi, W.Y., Lyere, P.A. and Adunyah, S.E. (2005) In Vitro Exposure to Quercetin and Genistein Alters Lipid Peroxides and Prevents the Loss of Glutathione in Human Progenitor Mononuclar (U937) Cells. Journal of Applied Toxicology, 25, 82-88.

[26]   Rimbach, G., Gohil, K., Matsugo, S., Moini, H., Saliou, C., Virgili, F., Weber, S.U. and Packer, L. (2001) Induction of Glutathione Synthesis in Human Keratinocytes by Ginkgo Biloba Extract (EG761). Biofactors, 15, 39-52.

[27]   Cowan, M.M. (1999) Plant Product as Antimicrobial Agents. Clinical Microbiology Reviews, 12, 564-582.

[28]   Cushnie, T.P.T. and Lamb, A.J. (2005) Antimicrobial Activity of Flavonoids. International Journal of Antimicrobial Agents, 26, 343-356.

[29]   Hoq, M.R., Karim, M.R. Arifuzzaman, M. and Mirza, A.H. (2015) Synthesis and Characterization of 2,2’-Bipyridyl-5,5’-dialdehyde Schiff Bases from O,S,N and F-Containing Amines. International Journal of Organic Chemistry, 5, 29-36.

[30]   Halliwell, B. (2007) Oxidative Stress and Cancer: Have We Moved Forward. Biochemical Journal, 401, 1-11.

[31]   Pohanka, M. (2014) Alzhimer’s Disease and Oxidative Stress: A Review. Current Medicinal Chemistry, 21, 356-364.

[32]   Hwang, O. (2013) Role of Oxidative Stress in Parkinson’s Disease. Experimental Neurobiology, 22, 11-17.

[33]   Pohanka, M. (2013) Role of Oxidative Stress in Infectious Diseases. A Review. Folia Microbiologica, 58, 503-513.

[34]   Singh, N., Dhalla, A.K., Seneviratne, C. and Singal, P.K. (1995) Oxidative Stress and Heart Failure. Molecular and Cellular Biochemistry, 147, 77-81.