Synthesis and in vitro α-glucosidase and cholinesterases inhibitory actions of watersoluble metallophthalocyanines bearing ({6-[3-(diethylamino)phenoxy]hexyl}oxy groups
Synthesis and in vitro α-glucosidase and cholinesterases inhibitory actions of watersoluble metallophthalocyanines bearing ({6-[3-(diethylamino)phenoxy]hexyl}oxy groups
In this paper, we have prepared peripherally tetra-({6-[3-(diethylamino)phenoxy]hexyl}oxy substituted cobalt(II), copper(II), manganese(III) phthalocyanines (3, 4, 5) and their water-soluble derivatives (3a, 4a, 5a). Then, in vitro α-glucosidase and cholinesterases inhibitory actions of the water-soluble 3a, 4a, 5a were examined using spectrophotometric methods. 4a had the highest inhibitory effects among the tested compounds against α-glucosidase due to $IC_{50}$ values. 4a and 5a had 40 fold higher inhibitory effects than the positive control. For cholinesterases, the compounds showed significant inhibitory actions that of galantamine which was used as a positive control. According to the SI value, 3a inhibited acetylcholinesterase enzyme selectively. In kinetic studies, 4a was a mixed inhibitor for α-glucosidase, 3a was a competitive inhibitor for AChE, and 4a was a mixed inhibitor for BuChE. The therapeutic potential of these compounds has been demonstrated by in vitro studies, but these data should be supported by further studies.
___
- 1. Chen SD, Yong TQ, Xiao C, Gao X, Xie YZ et al. Inhibitory effect of triterpenoids from the mushroom Inonotus obliquus against α-glucosidase and their interaction: Inhibition kinetics and molecular stimulations. Bioorganic Chemistry 2021; 115: 105276.
- 2. Tian JL, Si X, Wang YH, Gong ES, Xie X et al. Bioactive flavonoids from Rubus corchorifolius inhibit α-glucosidase and α-amylase to improve postprandial hyperglycemia. Food Chemistry 2021; 341: 128149.
- 3. Sherafati M, Mirzazadeh R, Barzegari E, Mohammadi-Khanaposhtani M, Azizian H et al. Quinazolinone-dihydropyrano [3, 2-b] pyran hybrids as new α-glucosidase inhibitors: Design, synthesis, enzymatic inhibition, docking study and prediction of pharmacokinetic. Bioorganic Chemistry 2021; 109: 104703.
- 4. Laakso M, Cederberg H. Glucose control in diabetes: which target level to aim for? Journal of Internal Medicine 2012; 272: 1-12.
- 5. Kausar N, Ullah S, Khan MA, Zafar H, Choudhary MI et al. Celebrex derivatives: Synthesis, α-glucosidase inhibition, crystal structures and molecular docking studies. Bioorganic Chemistry 2021; 106: 104499.
- 6. Guerrini R, Marzola E, Trapella C, Molinari S, Cerlesi MC et al. A novel and facile synthesis of tetra branched derivatives of nociceptin/ orphanin FQ. Bioorganic Medicinal Chemistry 2014; 22: 3703-3712.
- 7. Hamed YS, Abdin M, Rayan AM, Akhtar HMS, Zeng X. Synergistic inhibition of isolated flavonoids from Moringa oleifera leaf on α-glucosidase activity. LWT-Food Science and Technology, 2021; 141: 111081.
- 8. Phan MAT, Wang J, Tang J, Lee YZ, Ng K. Evaluation of α-glucosidase inhibition potential of some flavonoids from Epimedium brevicornum. LWT-Food Science and Technology 2013: 53: 492-498.
- 9. Kaur R, Kumar R, Dogra N, Yadav AK. Design, synthesis, biological evaluations and in silico studies of sulfonate ester derivatives of 2-(2-benzylidenehydrazono) thiazolidin-4-one as potential α-glucosidase inhibitors. Journal of Molecular Structure 2021; 1247: 131266.
- 10. Saeedi M, Hadjiakhondi A, Mohammad Nabavi S, Manayi A. Heterocyclic compounds: effective α-amylase and α-glucosidase inhibitors. Current Topics in Medicinal Chemistry 2017; 17: 428-440.
- 11. Almaz Z, Oztekin A, Tan A, Ozdemir H. Biological evaluation and molecular docking studies of 4-aminobenzohydrazide derivatives as cholinesterase inhibitors. Journal of Molecular Structure 2021; 244: 130918.
- 12. Kondapalli N, Sruthi K. Novel Tacrine and Hesperetin analogues: Design, Molecular docking and in silico ADME studies to identify potential Acetyl choline esterase inhibitors for Alzheimer’s disease. Journal of Faculty of Pharmacy of Ankara University 2020; 44: 18-32.
- 13. Haroon M, Khalid M, Shahzadi K, Akhtar T, Saba S et al. Alkyl 2-(2-(arylidene) alkylhydrazinyl) thiazole-4-carboxylates: Synthesis, Acetyl cholinesterase inhibition and docking studies. Journal of Molecular Structure 2021; 1245: 131063.
- 14. Ladner CJ, Lee JM. Pharmacological drug treatment of Alzheimer disease: the cholinergi hypothesis revisited. Journal of Neuropathology Experimental Neurology 1998; 57: 719-731.
- 15. Taha M, Alshamrani FJ, Rahim F, Uddin N, Chigurupati S et al. Synthesis, characterization, biological evaluation, and kinetic study of indole base sulfonamide derivatives as acetylcholinesterase inhibitors in search of potent anti-Alzheimer agent. Journal of King Saud University Science 2021; 33: 101401.
- 16. Francis PT, Palmer AM, Snape M, Wilcock GK. The cholinergic hypothesis of Alzheimer’s disease: a review of progress. Journal of Neurology Neurosurgery Psychiatry 1999; 66: 137-147.
- 17. Fang L, Chen M, Liu Z, Fang X, Gou S et al. Ferulic acid–carbazole hybrid compounds: combination of cholinesterase inhibition, antioxidant and neuroprotection as multifunctional anti-Alzheimer agents. Bioorganic Medicinal Chemistry 2016; 24: 886-893.
- 18. Mishra CB, Manral A, Kumari S, Saini V, Tiwari M. Design, synthesis and evaluation of novel indandione derivatives as multifunctional agents with cholinesterase inhibition, anti-β-amyloid aggregation, antioxidant and neuroprotection properties against Alzheimer’s disease. Bioorganic Medicinal Chemistry 2016; 24: 3829-3841.
- 19. Göksel M, Durmuş M, Bıyıklıoğlu Z. Synthesis and photodynamic activities of novel silicon(IV) phthalocyanines axially substituted with water soluble groups against HeLa cancer cell line. Dalton Transactions 2021; 50: 2570-2584.
- 20. Bilgiçli AT, Bilgiçli HG, Hepokur C, Tüzün B, Günsel A et al. Synthesis of (4R)-2-(3-hydroxyphenyl)thiazolidine-4-carboxylic acid substituted phthalocyanines: Anticancer activity on different cancer cell lines and molecular docking studies. Applied Organometallic Chemistry 2021; 35: e6242.
- 21. Cranston RR, Vebber MC, Rice NA, Tonnele C, Castet F et al. N-type solution-processed tin versus silicon phthalocyanines: A comparison of performance in organic thin-film transistors and in organic photovoltaics. ACS Applied Electronic Materials 2021; 3: 1873-1885.
- 22. Canımkurbey B, Taşkan MC, Demir S, Duygulu E, Atilla D et al. Synthesis and investigation of the electrical properties of novel liquid-crystal phthalocyanines bearing triple branched alkylthia chains. New Journal of Chemistry 2020; 44: 7424-7435.
- 23. Akyüz D, Koca A. Phthalocyanine-aniline dyad constructed with click electrochemistry: a novel hybrid electrochromic material. Journal of Solid State Electrochemistry 2020; 24: 431-440.
- 24. Güzel E, Baş H, Bıyıklıoğlu Z, Şişman İ. Dye-sensitized solar cells using silicon phthalocyanine photosensitizers with pyridine anchor: preparation, evaluation of photophysical, electrochemical and photovoltaic properties. Applied Organometallic Chemistry 2021; 35: e6214.
- 25. Ndebele N, Mgidlana S, Nyokong T. Electrocatalytic Activity of Cobalt Phthalocyanines Revisited: Effect of the Number of Oxygen Atoms and Conjugation to Carbon Nanomaterials. Electrocatalysis 2021; 12: 499-515.
- 26. Güzel E, Koçyiğit ÜM, Taslimi P, Erkan S, Taskin OS. Biologically active phthalocyanine metal complexes: Preparation, evaluation of α-glycosidase and anticholinesterase enzyme inhibition activities, and molecular docking studies. Journal of Biochemical Molecular Toxicology 2021; 35: e22765.
- 27. Arslan T, Çakır N, Keleş T, Bıyıklıoğlu Z, Şentürk M. Triazole substituted metal-free and metallophthalocyanines and their water soluble derivatives as potential cholinesterases ınhibitors for the treatment of Alzheimer’s disease: Design, synthesis, and in vitro inhibition study. Bioorganic Chemistry 2019; 90: 103100.
- 28. Keleş T, Barut B, Özel A, Bıyıklıoğlu Z. Design, synthesis and biological evaluation of water soluble and non-aggregated silicon phthalocyanines, naphthalocyanines against A549, SNU-398, SK-MEL128, DU-145, BT-20 and HFC cell lines as potential anticancer agents. Bioorganic Chemistry 2021; 107: 104637.
- 29. Atsay A, Gül A, Koçak MB. A new hexadeca substituted non-aggregating zinc phthalocyanine. Dyes and Pigments 2014; 100: 177-183.
- 30. Barut B, Bıyıklıoğlu Z, Yalçın CÖ, Abudayyak M. Non-aggregated axially disubstituted silicon phthalocyanines: Synthesis, DNA cleavage and in vitro cytotoxic/phototoxic anticancer activities against SH-SY5Y cell line. Dyes and Pigments 2020; 172: 107794.
- 31. Barut B, Yalçın CÖ, Demirbaş Ü. The water soluble Zn(II) and Mg(II) phthalocyanines: Synthesis, photochemical, DNA photodamage and PDT effects against A549 cells. Journal of Photochemistry and Photobiology A: Chemistry 2021; 405: 112946.
- 32. Bıyıklıoğlu Z, Çakır V, Çakır D, Kantekin H. Crown ether-substituted water soluble phthalocyanines and their aggregation, electrochemical studies. Journal of Organometallic Chemistry 2014; 749: 18-25.
- 33. Şen P. Yıldız SZ, Kanmazalp SD, Dege N. New Benzimidazole Substituted Cobalt and Manganese Phthalocyanines as Hydrogen Peroxide Catalysts for Laundry Bleaching. Macroheterocycles 2018; 11: 293-303.
- 34. Frasco MF, Fournier D, Carvalho F, Guilhermino L. Do metals inhibit acetylcholinesterase (AChE)? Implementation of assay conditions for the use of AChE activity as a biomarker of metal toxicity. Biomarkers 2005;10(5):360-75.
- 35. Arslan T. Design, synthesis of novel peripherally tetra-chalcone substituted phthalocyanines and their inhibitory effects on acetylcholinesterase and carbonic anhydrases (hCA I and II). Journal of Organometallic Chemistry2021; 951: 122021.
- 36. Barut B, Keleş T, Biyiklioglu Z, Yalçın CÖ. Peripheral or nonperipheral tetra-[4-(9H-carbazol-9-yl)phenoxy] substituted cobalt(II), manganese(III) phthalocyanines: Synthesis, acetylcholinesterase, butyrylcholinesterase, and α-glucosidase inhibitory effects and anticancer activities. Applied Organometallic Chemistry 2021; 35: e6021.