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Synthesis, protonation constants and biological activity determination of amino acid–salicylaldehyde-derived Schiff bases

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Abstract

Schiff bases represent a class of molecules widely studied for their importance in organic and coordination chemistry. Despite the large amount of studies on the chemical and biological properties of the Schiff bases, the different experimental conditions prevent a useful comparison to search for a correlation structure–activity. Moreover, literature is lacking in comprehensive data on the spectroscopic characterization of these compounds. For this reason, six Schiff bases, derived from salicylaldehyde and natural amino acids were fully characterized by nuclear magnetic resonance and infrared spectroscopy, and their aqueous solution equilibria, antiproliferative activity and DNA-binding activity were examined. All experimental conditions were kept constants to achieve comparable information and useful insights about their structure–activity correlation. The synthesized compounds showed DNA binding constants in the 101–102 M−1 range, depending on the substituent present in the amino acid side-chain, and resulted devoid of significant cytotoxic activity against the different human tumor cell lines showing IC50 values higher than 100 µM.

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References

  1. Ali AQ, Teoh SG, Salhin A, Eltayeb NE, Khadeer Ahamed MB, Abdul Majid AM (2014) Synthesis of isatin thiosemicarbazones derivatives: in vitro anti-cancer, DNA binding and cleavage activities. Spectrochim Acta A Mol Biomol Spectrosc 125:440–448. https://doi.org/10.1016/j.saa.2014.01.086

  2. Antony R, Arun T, Manickam STD (2019) A review on applications of chitosan-based Schiff bases. Int J Biol Macromol 129:615–633. https://doi.org/10.1016/j.ijbiomac.2019.02.047

  3. Arshad N, Ahmad M, Ashraf MZ, Nadeem H (2014) Spectroscopic, electrochemical DNA binding and in vivo anti-inflammatory studies on newly synthesized Schiff bases of 4-aminophenazone. J Photochem Photobiol B Biol 138:331–346. https://doi.org/10.1016/j.jphotobiol.2014.06.014

  4. Babu MSS, Reddy KH, Krishna PG (2007) Synthesis, characterization, DNA interaction and cleavage activity of new mixed ligand copper(II) complexes with heterocyclic bases. Polyhedron 26:572–580. https://doi.org/10.1016/j.poly.2006.08.026

  5. Banti CN, Hadjikakou SK, Sismanoglu T, Hadjiliadis N (2019) Anti-proliferative and antitumor activity of organotin(IV) compounds. An overview of the last decade and future perspectives. J Inorg Biochem 194:114–152

  6. Canel E, Gültepe A, Doğan A, Kilıç E (2006) The determination of protonation constants of some amino acids and their esters by potentiometry in different media. J Solut Chem 35:5–19. https://doi.org/10.1007/s10953-006-8934-3

  7. Chow MJ, Licona C, Wong DYQ, Pastorin G, Gaiddon C, Ang WH (2014) Discovery and investigation of anticancer ruthenium–arene Schiff-base complexes via water-promoted combinatorial three-component assembly. J Med Chem 57:6043–6059. https://doi.org/10.1021/jm500455p

  8. Dalapati S, Jana S, Guchhait N (2014) Anion recognition by simple chromogenic and chromo-fluorogenic salicylidene Schiff base or reduced-Schiff base receptors. Spectrochim Acta Part A Mol Biomol Spectrosc 129:499–508. https://doi.org/10.1016/j.saa.2014.03.090

  9. Dossetter AG, Jamison TF, Jacobsen EN (1999) Highly enantio- and diastereoselective hetero-Diels-Alder reactions catalyzed by new chiral tridentate chromium (III) catalysts. Angew Chem Int Ed Engl 38:2398–2400. https://doi.org/10.1002/(sici)1521-3773(19990816)38:16%3c2398:aid-anie2398%3e3.0.co;2-e

  10. El-Sherif AA, Aljahdali MS (2013) Review: protonation, complex-formation equilibria, and metal–ligand interaction of salicylaldehyde Schiff bases. J Coord Chem 66:3423–3468. https://doi.org/10.1080/00958972.2013.839027

  11. Ershov AY, Nasledov DG, Nasonova KV, Sezyavina KV, Susarova TV, Lagoda IV, Shamanin VV (2013) Ring-chain tautomerism of 2-aryl-6-oxohexahydropyrimidine-4-carboxylic acid sodium salts. Chem Heterocycl Compd 49:640–645. https://doi.org/10.1007/s10593-013-1287-0

  12. Galić N, Cimerman Z, Tomišić V (1997) Tautomeric and protonation equilibria of Schiff bases of salicylaldehyde with aminopyridines. Anal Chim Acta 343:135–143. https://doi.org/10.1016/S0003-2670(96)00586-7

  13. Gans P, O’Sullivan B (2000) GLEE, a new computer program for glass electrode calibration. Talanta 51:33–37. https://doi.org/10.1016/s0039-9140(99)00245-3

  14. Gans P, Sabatini A, Vacca A (1996) Investigation of equilibria in solution. Determination of equilibrium constants with the hyperquad suite of programs. Talanta 43:1739–1753. https://doi.org/10.1016/0039-9140(96)01958-3

  15. Gomes LMF, Vieira RP, Jones MR, Wang MCP, Dyrager C, Souza-Fagundes EM et al (2014) 8-Hydroxyquinoline Schiff-base compounds as antioxidants and modulators of copper-mediated Aβ peptide aggregation. J Inorg Biochem 139:106–116. https://doi.org/10.1016/j.jinorgbio.2014.04.011

  16. Gowri M, Jayabalakrishnan C (2012) DNA binding and cytotoxicity of newly synthesized Schiff base (Z)-4-(((2-hydroxyphenyl)amino)(phenyl)methylene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one and its analogues. Int J Appl Biol Pharm Technol 3:327–337

  17. Gran G (1952) Determination of the equivalence point in potentiometric titrations-Part II. Analyst 77:771

  18. Hiskey RG, Jung JM (1963) Azomethine chemistry. II. Formation of peptides from oxazolidine-5-ones. J Am Chem Soc 85:578–582. https://doi.org/10.1021/ja00888a021

  19. Hsieh SH, Kuo YP, Gau HM (2007) Synthesis, characterization, and structures of oxovanadium(V) complexes of Schiff bases of beta-amino alcohols as tunable catalysts for the asymmetric oxidation of organic sulfides and asymmetric alkynylation of aldehydes. Dalton Trans. https://doi.org/10.1039/b613212j

  20. Latt SA, Stetten G, Juergens LA, Willard HF, Scher CD (1975) Recent developments in the detection of deoxyribonucleic acid synthesis by 33258 Hoechst fluorescence. J Histochem Cytochem 23:493–505. https://doi.org/10.1177/23.7.1095650

  21. Liu X, Manzur C, Novoa N, Celedón S, Carrillo D, Hamon JR (2018) Multidentate unsymmetrically-substituted Schiff bases and their metal complexes: synthesis, functional materials properties, and applications to catalysis. Coord Chem Rev 357:144–172

  22. Liu S, Peng J, Yang H, Bai Y, Li J, Lai G (2012) Highly efficient and convenient asymmetric hydrosilylation of ketones catalyzed with zinc Schiff base complexes. Tetrahedron 68:1371–1375. https://doi.org/10.1016/j.tet.2011.12.054

  23. Malik MA, Dar OA, Gull P, Wani MY, Hashmi AA (2018) Heterocyclic Schiff base transition metal complexes in antimicrobial and anticancer chemotherapy. Med Chem Commun 9:409–436. https://doi.org/10.1039/c7md00526a

  24. Malinowski ER (2002) Factor analysis in chemistry, 3rd edn. Wiley, New York

  25. Maurya MR, Kumar U, Correia I, Adão P, Costa Pessoa J (2008) A polymer-bound oxidovanadium(IV) complex prepared from an l-cysteine-derived ligand for the oxidative amination of styrene. Eur J Inorg Chem. https://doi.org/10.1002/ejic.200700662

  26. Metzler CM, Cahill A, Metzler DE (1980) Equilibria and absorption spectra of Schiff bases. J Am Chem Soc 102:6075–6082. https://doi.org/10.1021/ja00539a017

  27. Michałowicz J, Duda W (2007) Phenols-sources and toxicity. Polish J Environ Stud 16:347–362

  28. Murmur J (1961) A procedure for the isolation of deoxyribonucleic acid from micro-organisms. J Mol Biol 3:208–218. https://doi.org/10.1016/S0022-2836(61)80047-8

  29. Palomo C, Aizpurua JM, Ganboa I, Oiarbide M (1999) Asymmetric synthesis of β-lactams by Staudinger Ketene-imine cycloaddition reaction. Eur J Org Chem. https://doi.org/10.1002/(SICI)1099-0690(199912)1999:12%3c3223:AID-EJOC3223%3e3.0.CO;2-1

  30. Pauwels R, Balzarini J, Baba M, Snoeck R, Schols D, Herdewijn P et al (1988) Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds. J Virol Methods 20:309–321. https://doi.org/10.1016/0166-0934(88)90134-6

  31. Pessoa JC, Mannar MR (2017) Vanadium complexes supported on organic polymers as sustainable systems for catalytic oxidations. Inorg Chim Acta 455:415–428

  32. Pillai MRA, Kothari K, Banerjee S, Samuel G, Suresh M, Sarma HD, Jurisson S (1999) Radiochemical studies of 99mTc complexes of modified cysteine ligands and bifunctional chelating agents. Nucl Med Biol 26:555–561

  33. Pivetta T, Trudu F, Valletta E, Isaia F, Castellano C, Demartin F et al (2014) Novel copper(II) complexes as new promising antitumour agents. A crystal structure of [Cu(1,10-phenanthroline-5,6-dione)2(OH2)(OClO3)](ClO4). J Inorg Biochem 141:103–113. https://doi.org/10.1016/j.jinorgbio.2014.08.011

  34. Pivetta T, Valletta E, Ferino G, Isaia F, Pani A, Vascellari S, Castellano C, Demartin F, Cabiddu MG, Cadoni E (2017) Novel coumarins and related copper complexes with biological activity: DNA binding, molecular docking and in vitro antiproliferative activity. J Inorg Biochem 177:101–109. https://doi.org/10.1016/j.jinorgbio.2017.09.013

  35. Qiao X, Ma ZY, Xie CZ, Xue F, Zhang YW, Xu JY et al (2011) Study on potential antitumor mechanism of a novel Schiff base copper(II) complex: synthesis, crystal structure, DNA binding, cytotoxicity and apoptosis induction activity. J Inorg Biochem 105:728–737. https://doi.org/10.1016/j.jinorgbio.2011.01.004

  36. Qin W, Long S, Panunzio M, Biondi S (2013) Schiff bases: a short survey on an evergreen chemistry tool. Molecules 18:12264–12289. https://doi.org/10.3390/molecules181012264

  37. Rajesh CM, Ray M (2014) Characterization of a meso-chiral isomer of a hexanuclear Cu(II) cage from racemization of the l-alanine Schiff base. Dalton Trans 43:12952–12960. https://doi.org/10.1039/c4dt01443j

  38. Rao G, Philipp M (1991) Boronic acid catalyzed hydrolyses of salicylaldehyde imines. J Org Chem 56:1505–1512. https://doi.org/10.1021/jo00004a031

  39. Reichmann ME, Rice SA, Thomas CA, Doty P (1954) A further examination of the molecular weight and size of desoxypentose nucleic acid. J Am Chem Soc 76:3047–3053. https://doi.org/10.1021/ja01640a067

  40. Saleem H, Erdogdu Y, Subashchandrabose S, Thanikachalam V, Jayabharathi J, Ramesh Babu N (2012) Structural and vibrational studies on (E)-2-(2-hydroxybenzylidenamino)-3-phenylpropionic acid using experimental and DFT methods. J Mol Struct 1030:157–167. https://doi.org/10.1016/j.molstruc.2012.04.011

  41. Smith HE, Burrows EP, Marks MJ, Lynch RD, Chen FM (1977) Optically active amines. 22. Application of the salicylidenimino chirality rule to α-amino acids. J Am Chem Soc 2:707–713. https://doi.org/10.1021/ja00445a008

  42. Turan B, Şendil K, Şengül E, Gültekin MS, Taslimi P, Gulcin I, Supuran CT (2016) The synthesis of some β- lactams and investigation of their metal-chelating activity, carbonic anhydrase and acetylcholinesterase inhibition profiles. J Enzyme Inhib Med Chem 31 (sup1):79–88

  43. Türkoğlu G, Berber H, Dal H, Öğretir C (2011) Synthesis, characterization, tautomerism and theoretical study of some new Schiff base derivatives. Spectrochim Acta A Mol Biomol Spectrosc 79:1573–1583. https://doi.org/10.1016/j.saa.2011.04.089

  44. Vilanova B, Gallardo J, Caldés C, Adrover M, Ortega-Castro J, Muñoz F et al (2012) Formation of Schiff bases of O-phosphorylethanolamine and O-phospho-d, l-serine with pyridoxal 5′-phosphate. Experimental and theoretical studies. J Phys Chem A 116:1897–1905. https://doi.org/10.1021/jp2116033

  45. Yang ZY, Yang RD, Li FS, Yu KB (2000) Crystal structure and antitumor activity of some rare earth metal complexes with Schiff base. Polyhedron 19:2599–2604. https://doi.org/10.1016/S0277-5387(00)00562-3

  46. Yoo J, Cui Q (2008) Does arginine remain protonated in the lipid membrane? Insights from microscopic pKa calculations. Biophys J Biophys Lett 94:L61–63. https://doi.org/10.1529/biophysj.107.122945

  47. Zhang N, Fan Y, Zhang Z, Zuo J, Zhang P, Wang Q et al (2012) Syntheses, crystal structures and anticancer activities of three novel transition metal complexes with Schiff base derived from 2-acetylpyridine and l-tryptophan. Inorg Chem Commun 22:68–72. https://doi.org/10.1016/j.inoche.2012.05.022

  48. Zhong X, Yi J, Sun J, Wei HL, Liu WS, Yu KB (2006) Synthesis and crystal structure of some transition metal complexes with a novel bis-Schiff base ligand and their antitumor activities. Eur J Med Chem 41:1090–1092. https://doi.org/10.1016/j.ejmech.2006.05.009

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Correspondence to Claudia Fattuoni or Tiziana Pivetta.

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Fattuoni, C., Vascellari, S. & Pivetta, T. Synthesis, protonation constants and biological activity determination of amino acid–salicylaldehyde-derived Schiff bases. Amino Acids (2020) doi:10.1007/s00726-019-02816-0

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Keywords

  • Schiff bases
  • l-Amino acids
  • DNA binding
  • Cytotoxicity
  • Aqueous solution equilibria