Ozlem OZDEMIR, Perihan GURKAN, Yaprak Dilber SIMAY DEMIR, Mustafa ARK

Antioxidant and Cytotoxic Activity Studies in Series of Higher Amino Acid Schiff Bases

In this work, the antioxidant activity of the higher amino acid Schiff bases, which were preparedas the monosodium salts (1a–3a) and the neutral forms (1b–3b) was determined by DPPHscavenging assay. In pure MeOH solution, the scavenging ability of Schiff bases 1a-3a werehigher than 1b-3b, but lower than ascorbic acid. The activity followed the order 3 (a,b) > 2 (a,b)> 1 (a,b). On the other hand, Schiff bases 2a and 3a behaved as the most effective scavengers ofthe DPPH radical in methanol-water mixture (v:v, 1:3). And, they were found to be have lowerSC50 values in this mixture compared to pure methanol. In vitro cytotoxicity of these Schiff baseswas studied against human cervical cancer cells (HeLa), human breast adenocarcinoma cells(MCF-7), and human normal embryonic kidney cells (HEK293). For HeLa cell line, Schiff bases1a-3a exhibited a litttle high activity than 1b, but very low activity than doxorubicin. Schiff bases2b and 3b had no cytotoxicity against HeLa cell. For MCF-7 cell line, Schiff bases 1a, 3a, 1b and3b nearly were inactive at 100 μM, whereas 2a increased cell proliferation in the all testedconcentration range. Differently, Schiff base 2b showed the highest cytotoxicity and killed 90percent of MCF-7 cells at concentration of 100 μM. For HEK-293, doxorubicin was stronglycytotoxic. Despite this, Schiff bases 1a, 3a and 3b were inactive, whereas the others showed littleweak toxicity.

PDF

___

[1] Ikram, M., Rehman, S., Khan, A., Baker, R.J., Hofer, T.S., Subhan, F., Qayum, M., Faridoon, Schulzke C., "Synthesis, characterization, antioxidant and selective xanthine oxidase inhibitory studies of transition metal complexes of novel amino acid bearing Schiff base ligand", Inorganica Chimica Acta, 428: 117–126, (2015).
[2] Blois, M. S., "Antioxidant determination by the use of a free radical", Nature, 181: 1199–1200, (1958).
[3] Beena, K., D., Rawat, D. S., "Synthesis and antioxidant activity of thymol and carvacrol based Schiff bases", Bioorganic and Medicinal Chemistry Letters, 23: 641–645, (2013).
[4] Pillai, R. R., Karrouchi, K., Fettach, S., Armakovic, S., Armakovic, S. J., Brik, Y., Taoufik, J., Radi, S., My Faouzi, E. A., Ansar, M., "Synthesis, spectroscopic characterization, reactive properties by DFT calculations, molecular dynamics simulations and biological evaluation of Schiff bases tethered 1,2,4-triazole and pyrazole rings", Journal of Molecular Structure, 1177: 47– 54, (2019).
[5] Cantuti-Castelvetri, I., Shukitt-Hale, B., Joseph, J. A., "Neurobehavioral aspects of antioxidants in aging", International Journal of Development Neuroscience, 18: 367–381, (2000).
[6] Amarowicz, R., Peggb, R. B., Rahimi-Moghaddam, P., Barld, B., Weil, J. A., "Free-radical scavenging capacity and antioxidant activity of selected plant species from the Canadian prairies", Food Chemistry, 84: 551–562, (2004).
[7] Menteşe, E., Yılmaz, F., Baltaş, N., Bekircan, O., Kahveci, B., "Synthesis and antioxidant activities of some new triheterocyclic compounds containing benzimidazole, thiophene, and 1,2,4- triazole rings", Journal of Enzym Inhibition and Medicinal Chemistry Early Online,1–7, (2014).
[8] Shanty, A. A., Mohanan, P. V., "Heterocyclic Schiff bases as nontoxic antioxidants: Solvent effect, structure activity relationship and mechanism of action", Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 192: 181–187, (2018).
[9] Rakesh, K. P., Kumara, H. K., Manukumar, H. M., Gowda, D. C., "Anticancer and DNA binding studies of potential amino acids based quinazolinone analogs: Synthesis, SAR and molecular docking", Bioorganic Chemistry, 87: 252–264, (2019).
[10] Chacko, S., Samanta, S., "A novel approach towards design, synthesis and evaluation of some Schiff base analogues of 2-aminopyridine and 2-aminobezothiazole against hepatocellular carcinoma", Biomedicine Pharmacotherapy, 89: 162–176, (2017).
[11] Shahraki, S., Delarami, H. S., Saeidifar, M., "Catalase inhibition by two Schiff base derivatives. Kinetics, thermodynamic and molecular docking studies", Journal of Molecular Liquid, 287: 111003, (2019).
[12] Ferri, N., Cazzaniga, S., Mazzarella, L., Curigliano, G., Lucchini, G., Zerla, D., Gandolfi, R., Facchetti, G., Pellizzoni, M., Rimoldi, I., "Cytotoxic effect of (1-methyl-1H-imidazol-2-yl)- methanamine and its derivatives in PtII complexes on human carcinoma cell lines: A comparative study with cisplatin", Bioorganic and Medicinal Chemistry, 21: 2379–2386, (2013).
[13] Ott, I., Gust, R., "Non Platinum Metal Complexes as Anti-cancer Drugs", Archiv der Pharmazie- Chemistry Life Sciences, 340: 117–126, (2007).
[14] Kaldır, H. M., Tatlı, E., Turgut, B., Vural, Ö., "Doksorubisin’e Bağlı Kardiyotoksisite", Turkiye Klinikleri Journal of Cardiology, 15: 416–421, (2002).
[15] Jin, V. X., Ranford, J. D., "Complexes of platinum(II) or palladium(II) with 1,10-phenanthroline and amino acids", Inorganica Chimica Acta, 304: 38–44, (2000).
[16] Bakalova, A., Varbanov, H., Buyukliev, R., Stanchev, S., Momekov, G., Ivanov, D., "Novel Pt(II) and Pt(IV) complexes with 3-amino-5-methyl-5-(4-pyridyl)-2,4-imidazolidenedione. Synthesis, physicochemical, chemometric and pharmacological investigation", Inorganica Chimica Acta, 363: 1568–1576 (2010).
[17] Shahraki, S., Majd, M. H., Heydari, A., "Novel tetradentate Schiff base zinc(II) complex as a potential antioxidant and cancer chemotherapeutic agent: Insights from the photophysical and computational approach", Journal of Molecular Structure, 1177: 536–544, (2019).
[18] Özdemir , Ö., Gürkan, P., Sarı, M., Tunç, T., "Synthesis of monosodium salts of N-(5-nitrosalicylidene)- D-amino acid Schiff bases and their iron(III) complexes: spectral and physical characterizations, antioxidant activities", Journal of Coordination Chemistry, 68: 2565–2585, (2015).
[19] Wang, H., Yuan, H., Li, S., Li, Z., Jiang, M., "Synthesis, antimicrobial activity of Schiff base compounds of cinnamaldehyde and amino acids", Bioorganic and Medicinal Chemistry Letters, 26: 809–813, (2016).
[20] Ganguly, R., Sreenivasulu, B., Vittal, J., "Amino acid-containing reduced Schiff bases as the building blocks for metallasupramolecular structures", Coordination Chemistry Reviews, 252: 1027–1050, (2008).
[21] Soares, S. M., Lemos, S. S., Sales, M. J. A., Burrow, R. A., "On the nuclearity of tricarbonyl rhenium(I) complexes with N,O,O-donating Schiff bases derived from amino acids", Journal of Organometallic Chemistry, 750: 80–85, (2014).
[22] Sevgi, F., Bagkesici, U., Kursunlu, A. N., Guler, E., "Fe (III), Co(II), Ni(II), Cu(II) and Zn(II) complexes of schiff bases based-on glycine and phenylalanine: Synthesis, magnetic/thermal properties and antimicrobial activity", Journal of Molecular Structure, 1154: 256–260, (2018).
[23] Abdel-Rahman, L. H., El-Khatib, R. M., Nassr, L. A. E., Abu-Dief, A. M., "DNA binding ability mode, spectroscopic studies, hydrophobicity, and in vitro antibacterial evaluation of some new Fe(II) complexes bearing ONO donors amino acid Schiff bases", Arabian Journal of Chemistry, 10: 1835–1846, (2017).
[24] Gupta, R., Mathur, M., Kumar Swami, A., Sharma, J., Singh, Y., "Synthesis and pharmacological activity of diorganoantimony(III) and triorganoantimony(V) derivatives of Schiff bases derived from amino acids", Journal of Saudi Chemical Society, 21: 67–75, (2017).
[25] Zhou, Y., Zhao, M., Wu, Y., Li, C., Wu, J., Zheng, M., Peng, L., Peng, S., "A class of novel Schiff’s bases: Synthesis, therapeutic action for chronic pain, anti-inflammation and 3D QSAR analysis", Bioorganic and Medicinal Chemistry, 18: 2165–2172, (2010).
[26] Zheng, J., Ma, L., "Silver(I) complexes of 2,4-dihydroxybenzaldehyde–amino acid Schiff bases: Novel noncompetitive α-glucosidase inhibitors", Bioorganic and Medicinal Chemistry Letters, 25: 2156–2161, (2015).
[27] Wang, R. M., Mao, J. J., Song, J. F., Huo, C. X., He, Y. F., "Antioxidant activity of bovine serum albümin binding amino acid Schiff-bases metal complexes", Chinese Chemical Letters, 18: 1416– 1418, (2007).
[28] Li, L-J., Fu, B., Qiao, Y., Wang, C., Huang, Y-Y., Liu, C-C., Tian, C., Du, J-L., "Synthesis, characterization and cytotoxicity studies of platinum(II) complexes with reduced amino acid ester Schiff-bases as ligands", Inorganica Chimica Acta, 419: 135–140, (2014).
[29] Alsalme, A., Laeeq, S., Dwivedi, S., Khan, M. S., Al Farhan, K., Musarrat, J., Khan, R. A., "Synthesis, characterization of α-amino acid Schiff base derived Ru/Pt complexes: Induces cytotoxicity in HepG2 cell via protein binding and ROS generation", Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 163: 1–7, (2016).
[30] Muche, S., Harms, K., Biernasiuk, A., Malm, A., Popiolek, L., Hordyjewska, A., Olszewska, A., Holynska, M., "New Pd(II) schiff base complexes derived from ortho-vanillin and L-tyrosine or L-glutamic acid: Synthesis, characterization, crystal structures and biological properties", Polyhedron, 151: 465–477, (2018).
[31] Sallam, S. A., Orabi, A. S., Abbas, A. M., "DNA interaction with octahedral and square planar Ni(II) complexes of aspartic-acid Schiff-bases", Journal of Molecular Structure, 1006: 272–281, (2011).
[32] Shahraki, S., Shiri, F., Saeidifar, M., "Evaluation of in silico ADMET analysis and human serum albumin interactions of a new lanthanum(III) complex by spectroscopic and molecular modeling studies", Inorganica Chimica Acta, 463: 80–87, (2017).
[33] Mahmood, S., Malik, M. A., Motevalli, M., Nunn, P. B., Q’Brien, P., "Synthesis and X-ray crystal structures of Schiff bases prepared from salicylaldehyde and the diamino acids L-2-amino-3- methylaminopropanoic acid, DL-2,4-diamino-butanoic acid and DL-2,3-diaminopropanoic acid", Tetrahedron, 54: 5721–5730, (1998).
[34] Yang, C. T., Vittal, J. J., "Synthesis and structural behavior of ternary copper(II) complexes containing reduced Schiff base N-(2-hydroxybenzyl)-4-am
[35] Puterova, Z., Valentova, J., Bojkova, Z., Kozisek, J., Devinsky, F., "Synthesis, crystal structure and antiradical effect of copper(II) Schiff base complexes containing five-, six- and unusual sevenmembered rings", Dalton Transactions, 40: 1484–1490, (2011).
[36] Güngör, Ö., Gürkan, P., "Synthesis and characterization of higher amino acid Schiff bases, as monosodium salts and neutral forms. Investigation of the intramolecular hydrogen bonding in all Schiff bases, antibacterial and antifungal activities of neutral forms", Journal of Molecular Structure, 1074: 62–70, (2014).
[37] Özdemir, Ö., "Studies on phenol-keto tautomerism, metal ion binding, and free radical scavenging properties of newly synthesized naphthalene-based tetraimine", Journal of BAUN Institute of Science and Technology, 20: 109–123, (2018).
[38] Özdemir, A., Şimay, Y. D., İbişoğlu, B., Yaren, B., Bülbül, D., Ark, M. "Cardiac glycosideinduced cell death and Rho/Rho kinase pathway: Implication of different regulation in cancer cell lines", Steroids, 109: 29–43, (2016).
[39] Zhang, Y., Fang, Y., Liang, H., Wang, H., Hu, K., Liu, X., Yi, X., Peng, Y., "Synthesis and antioxidant activities of 2-oxo-quinoline-3-carbaldehyde Schiff-base derivatives", Bioorganic and Medicinal Chemistry Letters, 23: 107–111, (2013).
[40] Porter, W. L., Antioxidants: Chemical, Physiological, Nutritional and Toxicological Aspects, (Williams,G.M.), Easton, USA, 93–122,(1993).
[41] Nenadis, N., Wang, L-F., Tsimidou, M., Zhang, H-Y., "Estimation of Scavenging Activity of Phenolic Compounds Using the ABTS.+ Assay", Journal of Agricultural and Food Chemistry, 52: 4669–4674, (2004).
[42] Sharma, O. P., Bhat, T. K., "DPPH antioxidant assay revisited", Food Chemistry, 113: 1202–1205, (2009).
[43] Sathiyaraj, S., Sampath, K., Butcher, R. J., Pallepogu, R., Jayabalakrishnan, C., "Designing, structural elucidation, comparison of DNA binding, cleavage, radical scavenging activity and anticancer activity of copper(I) complex with 5-dimethyl-2-phenyl-4-[(pyridin-2-ylmethylene)- amino]-1,2-dihydro-pyrazol-3-one Schiff base ligand", European Journal of Medicinal Chemistry, 64: 81–89, (2013).
[44] Brand-Williams, W., Cuvelier, M. E., Berset, C., "Use of a free radical method to evaluate antioxidant activity", Lebensmittel-Wissenschaft und Technologie, 28: 25–30, (1995).
[45] Thalamuthu, S., Annaraj, B., Neelakantan, M. A., "A systematic investigation on biological activities of a novel double zwitterionic Schiff base Cu(II) complex", Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 118: 120–129, (2014).
[46] Ratha, P., Chitra, L., Ancy, I., Kumaradhas, P., Palvannan, T., "New amino acid-Schiff base derived from s-allyl cysteine and methionine alleviates carbon tetrachloride-induced liver dysfunction", Biochimie, 138: 70–81, (2017).
[47] Adam, M. S. S., Elsawy, H., "Biological potential of oxo-vanadium salicylediene amino-acid complexes as cytotoxic, antimicrobial, antioxidant and DNA interaction", Journal of Photochemistry and Photobiology B, 184: 34–43, (2018).
[48] Özdemir, Ö., Gürkan, P., Şimay Demir, Y.D., Ark, M., "Novel palladium(II) complexes of N-(5- nitro-salicylidene)-Schiff bases: Synthesis, spectroscopic characterization and cytotoxicity investigation", Journal of Molecular Structure, 1207: 127852, (2020).
[49] John, L., Dasan, A., Joseyphus, R. S., Joe, I. H., "Molecular docking, structural characterization, DFT and cytotoxicity studies of metal(II) Schiff base complexes derived from thiophene-2- carboxaldehyde and l-histidine", Journal of Molecular Structure, 1198: 126934, (2019).
[50] Zhang, N., Fan, Y-h., Zhang, Z., Zuo, J., Zhang, P-f., Wang, Q., Liu, S-b., Bi, C-f., Syntheses, crystal structures and anticancer activities of three novel transition metal complexes with Schiff base derived from 2-acetylpyridine and l-tryptophan, Inorganic Chemistry Communications, 22: 68–72, (2012).