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Synthesis of some 3(2H)-pyridazinone and 1(2H)-phthalazinone derivatives incorporating aminothiazole moiety and investigation of their antioxidant, acetylcholinesterase, and butyrylcholinesterase inhibitory activities

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Abstract

In this study, 12 new compounds were synthesized, six of which were 3(2H)-pyridazinone (9a–f) and the others were 1(2H)-phthalazinone (10a–f) derivatives. The chemical structures of new compounds were confirmed by 1H-NMR, 13C-NMR, mass, and elemental analysis. The antioxidant properties of all the synthesized compounds were evaluated by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide radical scavenging assays. Moreover, cholinesterase inhibitory profiles of the synthesized compounds were determined using an in vitro assay based on a modified version of the Ellman protocol. Almost all the synthesized compounds displayed promising antioxidant activity, particularly in the DPPH radical scavenging assay, however, their inhibitory activities on cholinesterase enzymes pointed out structure specific interactions .

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References

  • Biran Y, Masters CL, Barnham KJ, Bush AI, Adlard PA (2009) Pharmacotherapeutic targets in Alzheimer’s disease. J Cell Mol Med 13(1):61–86

    Article  CAS  PubMed  Google Scholar 

  • Bolognesi ML, Bartolini M, Mancini F, Chiriano G, Ceccarini L, Rosini M, Milelli A, Tumiatti V, Andrisano V, Melchiorre C (2010) Bis(7)-tacrine derivatives as multitarget-directed ligands: focus on anticholinesterase and antiamyloid activities. Chem Med Chem 5(8):1215–1220

    Article  CAS  PubMed  Google Scholar 

  • Coates WJ, McKillop A (1993) One-pot preparation of 6-substituted 3(2H)-pyridazinones from ketones. Sythesis 3:334–342

    Article  Google Scholar 

  • Dasuri K, Zhang L, Keller JN (2013) Oxidative stress, neurodegeneration and the balance of protein degradation and protein synthesis. Free Radic Biol Med 62:170–185

    Article  CAS  PubMed  Google Scholar 

  • De S, Adhikari S, Tilak-Jain J, Menon VP, Devasagayam TPA (2008) Antioxidant activity of an aminothiazole compound: possible mechanisms. Chem Biol Interact 173:215–223

    Article  CAS  PubMed  Google Scholar 

  • Doğruer DS, Küpeli E, Yeşilada E, Sahin MF (2004) Synthesis of new 2-[1(2H)-phthalazinon-2-yl]acetamide and 3-[1(2H)-phthalazinon-2-yl]propanamide derivatives as antinociceptive and anti-inflammatory agents. Arch Pharm 337(6):303–310

    Article  Google Scholar 

  • Doğruer DS, Önkol T, Özkan S, Özgen S, Şahin MF (2008) Synthesis and antimicrobial activity of some 3(2H)-pyridazinone and 1(2H)-phthalazinone derivatives. Turk J Chem 32(4):469–479

    Google Scholar 

  • Droge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95

    CAS  PubMed  Google Scholar 

  • Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase. Biochem Pharmacol 7:88–95

    Article  CAS  PubMed  Google Scholar 

  • Fubini B, Hubbard A (2003) Reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation by silica in inflammation and fibrosis. Free Radic Biol Med 34(12):1507–1516

    Article  CAS  PubMed  Google Scholar 

  • Garcia AC, Pisani L, Nunez MC, Catto M, Nicolotti O, Leonetti F, Campos JM, Gallo MA, Espinosa A, Carotti A (2011) Homodimeric Bis-quaternary heterocyclic ammonium salts as potent acetyl-and butyrylcholinesterase inhibitors: a systematic investigation of the influence of linker and cationic heads over affinity and selectivity. J Med Chem 54:2627–2645

    Article  Google Scholar 

  • Geronikaki AA, Pitta EP, Liaras KS (2013) Thiazoles and thiazolidinones as antioxidants. Curr Med Chem 20(36):4460–4480

    Article  CAS  PubMed  Google Scholar 

  • Giacobini E (2004) Cholinesterase inhibitors: new roles and therapeutic alternatives. Pharmacol Res 50:433–440

    Article  CAS  PubMed  Google Scholar 

  • Hassanien AA (2003) Phthalazinone in heterocyclic synthesis: synthesis of some s-triazole, s-triazolothiadiazine, s-triazolothiadiazine, and s-triazolothiadiazole derivatives as pharmaceutical interest. Phosphorus Sulfur Silicon 178:199–1987

    Article  Google Scholar 

  • Kashyap SJ, Garg VK, Sharma PK, Kumar N, Dudhe R, Gupta JK (2012) Thiazoles: having diverse biological activities. Med Chem Res 21:2123–2132

    Article  CAS  Google Scholar 

  • Lü JM, Lin PH, Yao Q, Chen C (2010) Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems. J Cell Mol Med 14(4):840–860

    Article  PubMed Central  PubMed  Google Scholar 

  • Mirkov SM, Djordjevic AN, Andric NL, Andric SA, Kostic TS, Bogdanovic GM, Vojinovic-Miloradovc MB, Kovacevic RZ (2004) Nitric oxide-scavenging activity of polyhydroxylated fullerenol, C60(OH)24. Nitric Oxide-Biol Ch 11:201–207

    Article  CAS  Google Scholar 

  • Nitta Y, Yoneda F, Ohtaka T, Kato T (1964) Pyridazin-derivate. V. Synthese der derivative des 6-phenyl-3(2H)-pyridazinons. Chem Pharm Bull 12(1):69–73

    Article  CAS  PubMed  Google Scholar 

  • Özçelik AB, Gökçe M, Orhan I, Kaynak F, Sahin MF (2010) Synthesis and antimicrobial, acetylcholinesterase and butyrylcholinesterase inhibitory activities of novel ester and hydrazide derivatives of 3(2H)-pyridazinone. Arzneimittel-forsch 60(7):452–458

    Google Scholar 

  • Pinto M, Pickrell AM, Fukui H, Moraes CT (2013) Mitochondrial DNA damage in a mouse model of Alzheimer’s disease decreases amyloid beta plaque formation. Neurobiol Aging 34:2399–2407

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ramalingam M, Kim SJ (2012) Reactive oxygen/nitrogen species and their functional correlations in neurodegenerative diseases. J Neural Transm 119:891–910

    Article  CAS  PubMed  Google Scholar 

  • Salloway S, Mintzer J, Weiner MF, Cummings JL (2008) Disease-modifying therapies in Alzheimer’s disease. Alzheimer’s & Dementia 4:65–79

    Article  CAS  Google Scholar 

  • Schliebs R, Arendt T (2011) The cholinergic system in aging and neuronal degeneration. Behav Brain Res 221:555–563

    Article  CAS  PubMed  Google Scholar 

  • Seifried HE, Anderson DE, Fisher EI, Milner JA (2007) A review of the interaction among dietary antioxidants and reactive oxygen species. J Nutr Biochem 18(9):567–579

    Article  CAS  PubMed  Google Scholar 

  • Sharma OP, Bhat TK (2009) DPPH antioxidant assay revisited. Food Chem 113(4):1202–1205

    Article  CAS  Google Scholar 

  • Skoumalova´ A, Hort J (2012) Blood markers of oxidative stress in Alzheimer’s disease. J Cell Mol Med 16(10):2291–2300

    Article  PubMed  Google Scholar 

  • Şüküroğlu M, Yamalı C, Tiryaki D, Onurdag FK, Akkol E, Dogruer DS (2013) Synthesis of some new 3(2H)-pyridazinone derivatives and evaluation of their analgesic-anti-inflammatory and antimicrobial activities. Lett Drug Des Discov 10(6):507–514

    Article  Google Scholar 

  • Tiryaki D, Şüküroğlu M, Doğruer DS, Akkol E, Ozgen S, Şahin MF (2013) Synthesis of some new 2,6-disubstituted-3(2H)-pyridazinone derivatives and investigation of their analgesic, anti-inflammatory and antimicrobial activities. Med Chem Res 22:2553–2560

    Article  CAS  Google Scholar 

  • Usmar VD, Halliwell B (1996) Blood radicals: reactive nitrogen species, reactive oxygen species, transition metal ions, and the vascular system. Pharm Res 3(5):649–662

    Article  Google Scholar 

  • Wiseman H, Halliwell B (1996) Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Biochem J 313:17–29

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wolin MS (2000) Interactions of oxidants with vascular signaling systems. Arterioscler Thromb Vasc Biol 20:1430–1442

    Article  CAS  PubMed  Google Scholar 

  • Xing W, Fu Y, Shi Z, Lu D, Zhang H, Hua Y (2013) Discovery of novel 2,6-disubstituted pyridazinone derivatives as acetylcholinesterase inhibitors. Eur J Med Chem 63:95–103

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported financially with grant from Research Foundation of Gazi University (Project Number: 02/2012-39).

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Etiler, Ankara, Turkey

    Cem Yamalı, Burcu Kahya, M. Kadir Şüküroğlu & Deniz S. Doğruer

  2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Atatürk University, Erzurum, Turkey

    Cem Yamalı

  3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Eastern Mediterranean University, Gazimagosa, North Cyprus

    H. Ozan Gülcan

  4. Department of Biochemistry, Faculty of Pharmacy, Gazi University, Etiler, Ankara, Turkey

    Simla Çobanoğlu

Authors
  1. Cem Yamalı
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  2. H. Ozan Gülcan
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  3. Burcu Kahya
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  4. Simla Çobanoğlu
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  5. M. Kadir Şüküroğlu
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  6. Deniz S. Doğruer
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Corresponding author

Correspondence to Deniz S. Doğruer.

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Yamalı, C., Ozan Gülcan, H., Kahya, B. et al. Synthesis of some 3(2H)-pyridazinone and 1(2H)-phthalazinone derivatives incorporating aminothiazole moiety and investigation of their antioxidant, acetylcholinesterase, and butyrylcholinesterase inhibitory activities. Med Chem Res 24, 1210–1217 (2015). https://doi.org/10.1007/s00044-014-1205-8

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  • DOI: https://doi.org/10.1007/s00044-014-1205-8

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