SYNTHESIS AND FUNCTIONAL PROPERTIES OF DIPHENYLAMINE-CONTAINING SCHIFF BASES

Year 2023, Volume: 6 Issue: 1, 40 - 55, 31.07.2023

Hasan Ufuk Celebioglu , Ebru Köroğlu , Recep Taş , Sevilay Günay , Yavuz Erden

https://doi.org/10.55930/jonas.1278393

Abstract

Schiff bases have been widely researched in vitro for their antimicrobial, antitumor, antiviral, antineoplastic, and antioxidant properties, owing to their strong chelating ability. Probiotics refer to “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. Thus, this study aims to investigate the antibacterial, anticancer, and antioxidant effects of Schiff Bases N-methylene-N-phenylbenzenaminium and N-(5-oxopentylidene)-N-phenylbenzenaminium, as well as their impact on some properties of probiotic bacteria, Lactobacillus acidophilus and Lacticaseibacillus rhamnosus. Results indicate that these Schiff bases promote the growth of probiotic bacteria while inhibiting pathogenic bacteria. They demonstrate potent antibacterial and antioxidant activities, and cytotoxicity assays reveal that both compounds exert a high degree of inhibition on human colon and breast cancer cells. Additionally, there is significant modulation in auto-aggregation and surface hydrophobicity of Lactobacillus acidophilus and Lacticaseibacillus rhamnosus. In conclusion, the Schiff bases investigated in this study possess significant therapeutic potential.

Keywords

Antibacterial, anticancer, antioxidant, Lactobacillus, probiotics, Schiff bases

Supporting Institution

Bartın Üniversitesi

Project Number

2020-FEN-A-006

Thanks

The authors are grateful to Chr. Hansen, Turkey for the probiotic strains. This work was partly financed by Bartin University Scientific Research Project Coordination Unit (Project No: 2020-FEN-A-006).

References

• 1. Abbo, H.S., Titinchi, S.J.J., Prasad, R. & Chand, S. (2005). Synthesis, characterization and study of polymeric iron (III) complexes with bidentate p-hydroxy Schiff bases as heterogeneous catalysts. Journal of Molecular Catalysis a-Chemical.;225(2), 225-232.
• 2. Abd-Elzaher, M.M., Labib, A.A., Mousa, H.A., Moustafa, S.A., Ali, M.M. & El-Rashedy, A.A. (2016). Synthesis, anticancer activity and molecular docking study of Schiff base complexes containing thiazole moiety. Beni-Suef University Journal of Basic and Applied Sciences.5(1), 85-96.
• 3. Alander, M., Satokari, R., Korpela, R., Saxelin, M., Vilpponen-Salmela, T. Mattila-Sandholm, T. & von Wright, A. (1999). Persistence of colonization of human colonic mucosa by a probiotic strain, Lactobacillus rhamnosus GG, after oral consumption. Appl. Environ. Microbiol., 65(1), 351-354.
• 4. Aly, A.A., Hassan, A.A., Makhlouf, M.M. & Bräse, S. (2020). Chemistry and biological activities of 1,2,4-triazolethiones—antiviral and anti-infective drugs. Molecules. 25(13), 30-36.
• 5. Arena, M.P., Capozzi, V., Spano, G. & Fiocco, D. (2017). The potential of lactic acid bacteria to colonize biotic and abiotic surfaces and the investigation of their interactions and mechanisms. Applied Microbiology and Biotechnology, 101(7), 2641-2657.
• 6. Bayani, M.A. & Azanza, M.P.V. (2005). Inhibition of Staphylococcus aureus by garlic and NaCl in broth systems. Food Science and Technology Research.11(2), 214-221.
• 7. Bjarnsholt, T., Jensen, P.O., Rasmussen, T.B., Christophersen, L., Calum, H., Hentzer, M., Hougen, H.P., Rygaard, J., Moser, C., Ebert, L., Hoiby, N. & Givskov, M. (2005). Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections. Microbiology-Sgm. 151, 3873-3880.
• 8. Brandt, A.L., Castillo, A., Harris, K.B., Keeton, J.T., Hardin, M.D. & Taylor, T.M. (2010). Inhibition of Listeria monocytogenes by Food Antimicrobials Applied Singly and in Combination. Journal of Food Science. 75(9), M557-M563.
• 9. Bringmann, G., Dreyer, M., Faber, J.H., Dalsgaard, P.W., Staerk, D., Jaroszewski, J.W., Ndangalasi, H., Mbago, F., Brun, R. & Christensen, S.B. (2004). Ancistrotanzanine C and related 5,1 '- and 7,3 '-coupled naphthylisoquinoline alkaloids from Ancistrocladus tanzaniensis. Journal of Natural Products. 67(5), 743-748. 10. Buck, B.L., Altermann, E., Svingerud, T. & Klaenhammer, T.R. (2005). Functional analysis of putative adhesion factors in Lactobacillus acidophilus NCFM. Applied and Environmental Microbiology. 71(12), 8344-8351.
• 11. Capurso, L. (2019). Thirty years of Lactobacillus rhamnosus GG A Review. Journal of Clinical Gastroenterology. 53, S1-S41.
• 12. Çelebi, B., Taş, R., Akşit, A. & Celebioglu, H.U. (2020). Effects of loganic acid isolated from Vinca soneri on surface hydrophobicity and auto-aggregation of probiotic bacteria, Lactobacillus acidophilus and Lactobacillus rhamnosus. Erzincan University Journal of Science and Technology. 13(1), 115-122.
• 13. Celebioglu, H.U., Ejby, M., Majumder, A., Kobler, C., Goh, Y.J., Thorsen, K., Schmidt, B., Flaherty, S., Hachem, M.A., Lahtinen, S.J., Jacobsen, S., Klaenhammer, T.R., Brix, S., Molhave, K. & Svensson, B. (2016). Differential proteome and cellular adhesion analyses of the probiotic bacterium Lactobacillus acidophilus NCFM grown on raffinose - an emerging prebiotic. Proteomics. 16(9), 1361-1375.
• 14. Celebioglu, H.U., Kesici, A. & Taş, R. (2020a). Investigation of possibilities of using Nerium oleander L. extract as prebiotic for Lactobacillus acidophilus and Lactobacillus rhamnosus. Erzincan University Journal of Science and Technology. 13(3), 1147-1157.
• 15. Celebioglu, H.U., Erden, Y., Hamurcu, F., Taslimi, P., Şentürk, O.S., Özmen, Ü.Ö., Tuzun, B. & Gülçin, İ. (2020b). Cytotoxic effects, carbonic anhydrase isoenzymes, α-glycosidase and acetylcholinesterase inhibitory properties, and molecular docking studies of heteroatom-containing sulfonyl hydrazone derivatives. Journal of Biomolecular Structure and Dynamics, 1-12.
• 16. Celebioglu, H.U. & Svensson, B. (2018). Dietary nutrients, proteomes, and adhesion of probiotic lactobacilli to mucin and host epithelial cells. Microorganisms. 6(3).
• 17. Charalampopoulos, D., Pandiella, S.S. & Webb, C. (2002). Growth studies of potentially probiotic lactic acid bacteria in cereal-based substrates. Journal of Applied Microbiology. 92(5), 851-859.
• 18. Collado, M.C., Meriluoto, J. & Salminen, S. (2008). Adhesion and aggregation properties of probiotic and pathogen strains. European Food Research and Technology. 226(5), 1065-1073.
• 19. Dagogo-Jack, I & Shaw, A.T. (2018). Tumour heterogeneity and resistance to cancer therapies. Nat Rev Clin Oncol. 15(2), 81-94.
• 20. Das, A., Trousdale, M.D., Ren, S.J. & Lien, E.J. (1999). Inhibition of herpes simplex virus type 1 and adenovirus type 5 by heterocyclic Schiff bases of aminohydroxyguanidine tosylate. Antiviral Research. 44(3), 201-208.
• 21. De Souza, A.O., Galetti, F.C.S., Silva, C.L., Bicalho, B., Parma, M.M., Fonseca, S.F., Marsaioli, A.J., Trindade, A.C., Gil, R.P., Bezerra, F.S., Neto, M.A. & Oliveira, M.C. (2007). Antimycobacterial and cytotoxicity activity of synthetic and natural compounds. Quimica Nova. 30(7), 1563-1566.
• 22. Drisko, J.A., Giles, C.K. & Bischoff, B.J. (2003). Probiotics in health maintenance and disease prevention. Alternative medicine review.8(2), 143-155.
• 23. Durackova, Z., Mendiola, M.A., Sevilla, M.T. & Valent, A. (1999). Thiohydrazone copper(II) complexes. The relationship between redox properties and superoxide dismutase mimetic activity. Bioelectrochemistry and Bioenergetics. 48(1), 109-116.
• 24. Fioravanti, R., Biava, M., Donnarumma, S. & Porretta, G.C. (1996). Synthesis and microbiological evaluations of (N-heteroaryl)arylmethanamines and their Schiff bases. Farmaco. 51(10), 643-652.
• 25. Galini, M., Salehi, M., Kubicki, M., Amiri, A. & Khaleghian, A. (2017). Structural characterization and electrochemical studies of Co(II), Zn(II), Ni(II) and Cu(II) Schiff base complexes derived from 2-((E)-(2-methoxyphenylimino)methyl)-4-bromophenol; Evaluation of antioxidant and antibacterial properties. Inorganica Chimica Acta. 461, 167-173.
• 26. Gonzalez-Rodriguez, I., Ruiz, L., Gueimonde, M., Margolles, A. & Sanchez, B. (2013). Factors involved in the colonization and survival of bifidobacteria in the gastrointestinal tract. Fems Microbiology Letters. 340(1), 1-10.
• 27. Gupta, S. & Ravishankar, S. (2005). A comparison of the antimicrobial activity of garlic, ginger, carrot, and turmeric pastes against Escherichia coli O157 : H7 in laboratory buffer and ground beef. Foodborne Pathogens and Disease. 2(4), 330-340.
• 28. Hajrezaie, M., Paydar, M., Zorofchian Moghadamtousi, S., Hassandarvish, P., Gwaram, N.S., Zahedifard, M., Rouhollahi, E., Karimian, H., Looi, C.Y., Ali, H.M., Majid, N.A. & Abdulla, M.A. (2014). A Schiff Base-derived copper (II) complex is a potent inducer of apoptosis in colon cancer cells by activating the intrinsic pathway. The Scientific World Journal.
• 29. Hill, C., Guarner, F., Reid, G., Gibson, G.R., Merenstein, D.J., Pot, B., Morelli, L., Canani, R.B., Flint, H.J., Salminen, S., Calder, P.C. & Sanders, M.E. (2014). The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews Gastroenterology & Hepatology. 11(8), 506-514.
• 30. Holmes, E., Li, J.V., Marchesi, J.R.. & Nicholson, J.K. (2012). Gut microbiota composition and activity in relation to host metabolic phenotype and disease risk. Cell Metabolism. 16(5), 559-564.
• 31. Iftikhar, B., Javed, K., Khan, M.S.U., Akhter, Z., Mirza, B. & Mckee, V. (2018). Synthesis, characterization and biological assay of Salicylaldehyde Schiff base Cu(II) complexes and their precursors. Journal of Molecular Structure. 1155, 337-348.
• 32. Iqbal, A., Siddiqui, H.L., Ashraf, C.M., Ahmad, M. & Weaver, G.W. (2007). Synthesis, characterization and antibacterial activity of azomethine derivatives derived from 2-formylphenoxyacetic acid. Molecules. 12(2), 245-254.
• 33. Kedare, S.B. & Singh, R.P. (2011). Genesis and development of DPPH method of antioxidant assay. Journal of Food Science and Technology-Mysore. 48(4), 412-422.
• 34. Khan, S.A., Asiri, A.M. & Sharma, K. (2017). Efficient microwave assisted synthesis and computational study of isoxazole Schiff base as an antibacterial agent. Indian Journal of Chemistry Section B-Organic Chemistry Including Medicinal Chemistry. 56(4), 453-457.
• 35. Krishna, K.M., Inturi, B., Pujar, G.V., Madhusudan, N.P. & Vijaykumar, G.S. (2014). Design, synthesis and 3D-QSAR studies of new diphenylamine containing 1,2,4-triazoles as potential antitubercular agents. European Journal of Medicinal Chemistry, 84(12), 516-529.
• 36. Kos, B., Suskovic, J., Vukovic, S., Simpraga, M., Frece, J. & Matosic, S. (2003). Adhesion and aggregation ability of probiotic strain Lactobacillus acidophilus M92. Journal of Applied Microbiology. 94(6), 981-987.
• 37. Köroğlu, E., Celebioglu, H.U., Akşit, H. & Taş, R. (2019). Insight into effects of ipolamiide isolated from Plantago euphratica on probiotic properties of Lactobacillus acidophilus and Lactobacillus rhamnosus. European Journal of Science and Technology. 17, 995-1000.
• 38. Kumar, S., Dhar, D.N. & Saxena, P.N. (2009). Applications of metal complexes of Schiff bases-A review. Journal of Scientific & Industrial Research. 68(3), 181-187.
• 39. Kumar, A. & Mishra, A.K. (2018). Pharmacological applications of diphenylamine and its derivative as potent bioactive compound: A Review. Current Bioactive Compounds. 14(3), 217-233.
• 40. Laparra, J.M. & Sanz, Y. (2009). Comparison of in vitro models to study bacterial adhesion to the intestinal epithelium. Letters in Applied Microbiology. 49(6), 695-701.
• 41. Liberta, A.E. & West, D.X. (1992). Antifungal and antitumor-activity of heterocyclic thiosemicarbazones and their metal-complexes - Current Status. Biometals. 5(2), 121-126.
• 42. Liu, Y.T., Sheng, J., Yin, D.W., Xin, H., Yang, X.M., Qiao, Q.Y. & Yang, Z.J. (2018). Ferrocenyl chalcone-based Schiff bases and their metal complexes: Highly efficient, solvent-free synthesis, characterization, biological research. Journal of Organometallic Chemistry. 856, 27-33.
• 43. Lu, C., Eskandari, A., Cressey, P.B. & Suntharalingam, K. (2017). Cancer stem cell and bulk cancer cell active Copper(ii) complexes with vanillin Schiff base derivatives and naproxen. Chemistry – A European Journal. 23(47), 11366-11374.
• 44. Mamedova, G., Mahmudova, A., Mamedov, S., Erden, Y., Taslimi, P., Tüzün, B., Tas, R., Farzaliyev, V., Sujayev, A., Alwasel, S.H. & Gulçin, İ. (2019). Novel tribenzylaminobenzolsulphonylimine based on their pyrazine and pyridazines: Synthesis, characterization, antidiabetic, anticancer, anticholinergic, and molecular docking studies. Bioorganic Chemistry 93, 103313.
• 45. Michel-Barba, M.G., Espinosa-Andrews, H., Garcia-Reyes, R.A., Desjardins, Y. & Gonzalez-Avila, M. (2019). Effect of blueberry extract, carriers, and combinations on the growth rate of probiotic and pathogenic bacteria. International Journal of Food Sciences and Nutrition. 70(1), 63-70.
• 46. Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival - application to proliferation and cyto-toxicity assays. Journal of Immunological Methods. 65(1-2), 55-63.
• 47. Mousavi, Z.E., Mousavi, S.M., Razavi, S.H., Emam-Djomeh, Z. & Kiani, H. (2011). Fermentation of pomegranate juice by probiotic lactic acid bacteria. World Journal of Microbiology & Biotechnology. 27(1), 123-128.
• 48. Özçelik, G.G.F. (2014). Probiotic use of bacteriocin producing lactic acid bacteria. Academic Food. 12(1), 63-68.
• 49. Parekh, N.M., Mistry, B.M., Pandurangan, M., Shinde, S.K. & Patel, R.V. (2017). Investigation of anticancer potencies of newly generated Schiff base imidazolylphenylheterocyclic-2-ylmethylenethiazole-2-amines. Chinese Chemical Letters. 28(3), 602-606.
• 50. Pedersen, K. & Tannock, G.W. (1989). Colonization of the porcine gastrointestinal tract by lactobacilli. Appl. Environ. Microbiol., 55(2), 279-283.
• 51. Percival, G.C., Chamundeeswari, M., Lovlyna, F.R., Seethalakshmi, R. & Sreekumar, G. (2019). Production and partial purification of beta-galactosidase enzyme from probiotic Bacillus subtilis SK09. Indian Journal of Biotechnology. 18(2), 139-144.
• 52. Roy, F. (1992). History and development of probiotics. In: Probiotics. In. Dordrecht: Springer.
• 53. Servin, A.L. & Coconnier, M.H. (2003). Adhesion of probiotic strains to the intestinal mucosa and interaction with pathogens. Best Practice & Research Clinical Gastroenterology. 17(5), 741-754.
• 54. Shanty, A.A., Philip, J.E., Sneha, E.J., Kurup, M.R.P., Balachandran, S. & Mohanan, P.V. (2017). Synthesis, characterization and biological studies of Schiff bases derived from heterocyclic moiety. Bioorganic Chemistry. 70, 67-73.
• 55. Shi, L., Ge, H.M., Tan, S.H., Li, H.Q., Song, Y.C., Zhu, H.L. & Tan, R.X. (2007). Synthesis and antimicrobial activities of Schiff bases derived from 5-chloro-salicylaldehyde. European Journal of Medicinal Chemistry. 42(4), 558-564.
• 56. Siciliano, R.A. & Mazzeo, M.F. (2012). Molecular mechanisms of probiotic action: a proteomic perspective. Current Opinion in Microbiology. 15(3), 390-396.
• 57. Sur, B., Chatterjee, S.P., Sur, P., Maity, T. & Roychoudhury, S. (1990). Studies on the Antineoplasticity of Schiff-Bases Containing 5-Nitrofuran and Pyrimidine. Oncology. 47(5), 433-438.
• 58. Sutherland, J., Miles, M., Hedderley, D., Li, J., Devoy, S., Sutton, K. & Lauren, D. (2009). In vitro effects of food extracts on selected probiotic and pathogenic bacteria. International Journal of Food Sciences and Nutrition. 60(8), 717-727.
• 59. Taslimi, P., Erden, Y., Mamedov, S., Zeynalova, L., Ladokhina, N., Tas, R., Tuzun, B., Sujayev, A., Sadeghian, N., Alwasel, S.H. & Gulcin, İ. (2021). The biological activities, molecular docking studies, and anticancer effects of 1-arylsuphonylpyrazole derivatives. Journal of Biomolecular Structure and Dynamics 39(9), 3336-3346.
• 60. Tekin, S., Erden, Y., Sandal, S. & Yilmaz, B. (2015). Is irisin an anticarcinogenic peptide? Medicine Science. 4(2), 2172-2180.
• 61. Tidwell, T.T. (2008). Hugo (ugo) Schiff, Schiff bases, and a century of beta-lactam synthesis. Angewandte Chemie-International Edition. 47(6), 1016-1020.
• 62. Van Tassell, M.L. & Miller, M.J. (2011). Lactobacillus Adhesion to Mucus. Nutrients. 3(5), 613-636.
• 63. Xia, Y., Liu, X., Zhang, L., Zhang, J., Li, C., Zhang, N., Xu, H. & Li, Y. (2019). A new Schiff base coordinated copper(II) compound induces apoptosis and inhibits tumor growth in gastric cancer. Cancer Cell Int. 19, 81.
• 64. Yang, Z.Y., Yang, R.D., Li, F.S. & Yu, K.B. (2000). Crystal structure and antitumor activity of some rare earth metal complexes with Schiff base. Polyhedron. 19(26-27), 2599-2604.