Startseite Water soluble biguanide salts and their 1,3,5-triazine derivatives as inhibitors of acetylcholinesterase and α-glucosidase
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Water soluble biguanide salts and their 1,3,5-triazine derivatives as inhibitors of acetylcholinesterase and α-glucosidase

  • Ozge Gungor , Seda Nur Kertmen Kurtar und Muhammet Kose EMAIL logo
Veröffentlicht/Copyright: 31. August 2020
Veröffentlichen auch Sie bei De Gruyter Brill
Manuskript einreichen Informationen für Autor*innen
Zeitschrift für Kristallographie - Crystalline Materials
Aus der Zeitschrift Zeitschrift für Kristallographie - Crystalline Materials Band 235 Heft 10

Abstract

Seven biguanide derivatives were prepared by the nucleophilic reaction between dicyandiamide and p-substitute aniline derivatives or memantine or adamantine under acidic conditions. The cyclization of the biguanide compounds were also conducted via acetone to give 1,3,5-triazine derivatives. The structures of the synthesized compounds were characterized by analytical methods. The solid state structures of [HL5]Cl, [H2L7]Cl2, [HL1a]Cl and [HL5a]Cl were investigated by X-ray diffraction study. The acetylcholinesterase and α-glucosidase inhibitor properties of the compounds were then evaluated by the spectroscopic method. The compounds were found to show considerable acetylcholinesterase and α-glucosidase inhibitory activities compared to the approved drugs. The cyclization of biguanide derivatives with acetone did not affect inhibition of acetylcholinesterase, yet increased the α-glucosidase inhibition.

Keywords: acetylcholinesterase (AChE); biguanide; inhibitor; molecular structure; α-glucosidase; 1,3,5-triazine
Corresponding author: Muhammet Kose, Chemistry Department, Kahramanmaras Sutcu Imam University, Kahramanmaras, 46050, Turkey, Email:

Funding source: The Research Unit of Kahramanmaras Sutcu Imam University, Turkey

Award Identifier / Grant number: 2018/5-17M

Award Identifier / Grant number: 2019/6-22M

Funding source: Turkish Council of Higher Education

Award Identifier / Grant number: YOK 100/2000

Acknowledgments

We are grateful to The Research Unit of Kahramanmaras Sutcu Imam University, Turkey, for the financial support of this work (Project numbers: 2018/5-17M, 2019/6-22M). We also thank to the Turkish Council of Higher Education for the award (YOK 100/2000) of a postgraduate scholarship (to SNKK and OG).

  1. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  2. Research funding: This work was supported by The Research Unit of Kahramanmaras Sutcu Imam University, Turkey, for the financial support of this work (Project numbers: 2018/5-17M, 2019/6-22M). We also thank to the Turkish Council of Higher Education for the award (YOK 100/2000) of a postgraduate scholarship (to SNKK and OG).

  3. Conflict of interest statement: Authors state no conflict of interest.

References

1. Oliveira, C., Bagetta, D., Cagide, F., Teixeira, J., Amorim, R., Silva, T., Garrido, J., Remi, F., Uriarte, E., Oliveira, P. J., Alcaro, S., Ortuso, F., Alcaro, S. Benzoic acid-derived nitrones: a new class of potential acetylcholinesterase inhibitors and neuroprotective agents. Eur. J. Med. Chem. 2019, 174, 116; https://doi.org/10.1016/j.ejmech.2019.04.026.Suche in Google Scholar

2. Santos, T.-C.-D., Gomes, T. M., Pinto, B. A. S., Camara, A. L., Paes, A. M. D. A. Naturally occurring acetylcholinesterase inhibitors and their potential use for Alzheimer’s disease therapy. Front. Pharmacol. 2018, 9, 1192; https://doi.org/10.3389/fphar.2018.01192.Suche in Google Scholar

3. Song, Q., Li, Y., Cao, Z., Qiang, X., Tan, Z., Deng, Y. Novel salicylamide derivatives as potent multifunctional agents for the treatment of Alzheimer’s disease: Design, synthesis and biological evaluation. Bioorg. Chem. 2019, 84, 137; https://doi.org/10.1016/j.bioorg.2018.11.022.Suche in Google Scholar

4. Chigurupati, S., Selvaraj, M., Mani, V., Selvarajan, K. K., Mohammad, J. I., Kaveti, B., Bera, H., Palanimuthu, V. R., Teh, L. K., Salleh, M. Z. Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies. Bioorg. Chem. 2016, 67, 9–17; https://doi.org/10.1016/j.bioorg.2016.05.002.Suche in Google Scholar

5. Bhaskar, V., Chowdary, R., Dixit, S. R., Joshi, S. D. Synthesis, molecular modeling and BACE-1 inhibitory study of tetrahydrobenzo [b] pyran derivatives. Bioorg. Chem. 2019, 84, 202; https://doi.org/10.1016/j.bioorg.2018.11.023.Suche in Google Scholar

6. Si, W., Zhang, T., Zhang, L., Mei, X., Dong, M., Zhang, K., Ning, J. Design, synthesis and bioactivity of novel phthalimide derivatives as acetylcholinesterase inhibitors. Bioorg. & Med. Chem. Lett. 2016, 26, 2380; https://doi.org/10.1016/j.bmcl.2015.07.052.Suche in Google Scholar

7. Więckowska, A., Kołaczkowski, M., Bucki, A., Godyń, J., Marcinkowska, M., Więckowski, K., Wieckowski, K., Zareba, P., Siwek, A., Kazek, G., Głuch-Lutwin, M., Mierzejewski, P., Bienkowski, P., Sienkiewicz-Jarosz, H., Knez, D., Wichur, T., Gobec, S., Mierzejewski, P. Novel multi-target-directed ligands for Alzheimer’s disease: combining cholinesterase inhibitors and 5-HT6 receptor antagonists. Design, synthesis and biological evaluation. Eur. J. Med. Chem. 2016, 124, 63; https://doi.org/10.1016/j.ejmech.2016.08.016.Suche in Google Scholar

8. Turkan, F., Cetin, A., Taslimi, P., Karaman, M., Gulçin, İ. Synthesis, biological evaluation and molecular docking of novel pyrazole derivatives as potent carbonic anhydrase and acetylcholinesterase inhibitors. Bioorg. Chem. 2019, 86, 420–427; https://doi.org/10.1016/j.bioorg.2019.02.013.Suche in Google Scholar

9. Sonmez, F., Zengin Kurt, B., Gazioglu, I., Basile, L., Dag, A., Cappello, V., Ginex, T., Kucukislamoglu Guccione, M., Design, S. Synthesis and docking study of novel coumarin ligands as potential selective acetylcholinesterase inhibitors. J. Enzym. Inhib. Med. Chem. 2017, 32, 285; https://doi.org/10.1080/14756366.2016.1250753.Suche in Google Scholar

10. Mumtaz, A., Majeed, A., Zaib, S., Rahman, S. U., Hameed, S., Saeed, A., Rafiqued, H., Mughald, E., Maalike, A., Hussainf, I., Iqbal, J. Investigation of potent inhibitors of cholinesterase based on thiourea and pyrazoline derivatives: Synthesis, inhibition assay and molecular modeling studies. Bioorg. Chem. 2019, 90, 103036; https://doi.org/10.1016/j.bioorg.2019.103036.Suche in Google Scholar

11. Pisani, L., Catto, M., De Palma, A., Farina, R., Cellamare, S., Altomare, C. D. Discovery of potent dual binding site acetylcholinesterase inhibitors via homo-and heterodimerization of coumarin-based moieties. ChemMedChem 2017, 12, 1349; https://doi.org/10.1002/cmdc.201700282.Suche in Google Scholar

12. Mahdavi, M., Saeedi, M., Gholamnia, L., Jeddi, S. A. B., Sabourian, R., Shafiee, A., Foroumadi, A., Akbarzadeh, T. Synthesis of novel tacrine analogs as acetylcholinesterase inhibitors. J. Heterocycl. Chem. 2017, 54, 384; https://doi.org/10.1002/jhet.2594.Suche in Google Scholar

13. Kumar, J., Gill, A., Shaikh, M., Singh, A., Shandilya, A., Jameel, E., Sharma, N., Mrinal, N., Hoda, N., Jayaram, B. Pyrimidine-triazolopyrimidine and pyrimidine-pyridine hybrids as potential acetylcholinesterase inhibitors for alzheimer’s disease. Chem. Scr. 2018, 3, 736; https://doi.org/10.1002/slct.201702599.Suche in Google Scholar

14. Kumar, K., Kumar, A., Keegan, R. M., Deshmukh, R. Recent advances in the neurobiology and neuropharmacology of Alzheimer’s disease. Biomed. Pharmacother. 2018, 98, 297; https://doi.org/10.1016/j.biopha.2017.12.053.Suche in Google Scholar

15. Yiğit, B., Yiğit, M., Barut Celepci, D., Gök, Y., Aktaş, A., Aygün, M., Taslimi, P., Gülçin, İ. Novel benzylic substituted imidazolinium, tetrahydropyrimidinium and tetrahydrodiazepinium salts: potent carbonic anhydrase and acetylcholinesterase inhibitors. Chem. Sel. 2018, 3, 7976; https://doi.org/10.1002/slct.201801019.Suche in Google Scholar

16. Poovitha, S., Parani, M. In vitro and in vivo α-amylase and α-glucosidase inhibiting activities of the protein extracts from two varieties of bitter gourd (Momordica charantia L.). BMC Complement. Altern. Med. 2016, 16, 1; https://doi.org/10.1186/s12906-016-1085-1.Suche in Google Scholar

17. Adib, M., Peytam, F., Rahmanian-Jazi, M., Mahernia, S., Bijanzadeh, H.R., Jahani, M., Mohammadi-Khanaposhtani, M., Imanparast, S., Faramarzi, M. A., Mahdavi, M., Larijani, B. New 6-amino-pyrido[2,3-d]pyrimidine-2,4-diones as novel agents to treat type 2 diabetes: A simple and efficient synthesis, α-glucosidase inhibition, molecular modeling and kinetic study. Eur. J. Med. Chem. 2018, 155, 353; https://doi.org/10.1016/j.ejmech.2018.05.046.Suche in Google Scholar

18. Kathuria, D., Bankar, A. A., Bharatam, P. V. “What’s in a structure?” The story of biguanides. J. Mol. Struct. 2018, 1152, 61; https://doi.org/10.1016/j.molstruc.2017.08.100.Suche in Google Scholar

19. Slotta, K. H., Tschesche, R., Biguanide, ÜII. Die blutzucker-senkende Wirkung der Biguanide. Berichte Detsch. Chem. Ges. (A and B Ser.) 1929, 62, 1398; https://doi.org/10.1002/cber.19290620605.Suche in Google Scholar

20. Higurashi, T., Hosono, K., Takahashi, H., Komiya, Y., Umezawa, S., Sakai, E., Uchiyama, T., Taniguchi, L., Hata, Y., Uchiyama, S., Hattori, A., Nagase, H., Kessoku, T., Arimoto, J., Matsuhashi, N., Inayama, Y., Yamanaka, S., Taguri, M., Hattori, A. Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial. Lancet Oncol. 2016, 17, 475; https://doi.org/10.1016/s1470-2045(15)00565-3.Suche in Google Scholar

21. Markowicz-Piasecka, M., Sikora, J., Mateusiak, Ł., Mikiciuk-Olasik, E., Huttunen, K. M. Metformin and its sulfenamide prodrugs inhibit human cholinesterase activity. Oxid. Med. Cell. Longev. 2017, 2017, 7303096; https://doi.org/10.1155/2017/7303096.Suche in Google Scholar

22. Markowicz-Piasecka, M., Sikora, J., Mateusiak, Ł., Mikiciuk-Olasik, E., Huttunen, K. M. Metformin–a future therapy for neurodegenerative diseases. Pharm. Res. 2017, 34, 2614; https://doi.org/10.1007/s11095-017-2199-y.Suche in Google Scholar

23. Rotermund, C., Machetanz, G., Fitzgerald, J. C. The therapeutic potential of metformin in neurodegenerative diseases. Front. Endocrinol. 2018, 9, 400; https://doi.org/10.3389/fendo.2018.00400.Suche in Google Scholar

24. APEX and SAINT. Area Detector Control & Integration Software; SADABS, Program for Scaling and Correction of Area Detector Data; Bruker AXS Inc.: Madison, Wisconsin, USA, 2009.Suche in Google Scholar

25.a) Sheldrick, G. M. SHELXT – Integrated space-group and crystal-structure determination. Acta Crystallogr. 2015, A71, 3; https://doi.org/10.1107/s2053273314026370.Suche in Google Scholar

25.b) Sheldrick, G. M. Crystal structure refinement with SHELXL. Acta Crystallogr. 2015, C71, 3; https://doi.org/10.1107/s2053229614024218.Suche in Google Scholar

26. Werner, E., Bell, J. The preparation of methylguanidine, and of ββ-dimethylguanidine by the interaction of dicyanodiamide, and methylammonium and dimethylammonium chlorides respectively. J. Chem. Soc. Trans. 1922, 121, 1790; https://doi.org/10.1039/ct9222101790.Suche in Google Scholar

27. Ma, X., Poon, T. Y., Wong, P. T. H., Chui, W. K. Synthesis and in vitro evaluation of 2, 4-diamino-1, 3, 5-triazine derivatives as neuronal voltage-gated sodium channel blockers. Bioorg. & Med. Chem. Lett. 2009, 19, 5644; https://doi.org/10.1016/j.bmcl.2009.08.052.Suche in Google Scholar

28. Ellman, G. L., Courtney, K. D., Andres, V., Feather-Stone, R. M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 1961, 7, 88; https://doi.org/10.1016/0006-2952(61)90145-9.Suche in Google Scholar

29. Jabeen, F., Oliferenko, P. V., Oliferenko, A. A., Pillai, G. G., Ansari, F. L., Hall, C. D., Katritzky, A. R. Dual inhibition of the α-glucosidase and butyrylcholinesterase studied by Molecular Field Topology Analysis. Eur. J. Med. Chem. 2014, 80, 228; https://doi.org/10.1016/j.ejmech.2014.04.018.Suche in Google Scholar

30. Mohsen, U. A., Kaymakcıoglu, B. K., Oruc-Emre, E. E., Kaplanc ıklı, Z. A., Rollas, S. Studies on hydrazideehydrazones derivatives as acetylcholinesterase inhibitors. Musbed 2015, 1, 10.10.5455/musbed.20141117035707Suche in Google Scholar

31. Karaman, N., Sıcak, Y., Tok, T. T., Oztürk, M., Iyidogan, A. K., Dikmen, M., Kaymakçıoglu, €. B. K., Oruç-Emre, E. E. New piperidine-hydrazone derivatives: synthesis, biological evaluations and molecular docking studies as AChE and BChE inhibitors. Eur. J. Med. Chem. 2016, 124, 270; https://doi.org/10.1016/j.ejmech.2016.08.037.Suche in Google Scholar

32. Alonso, D., Dorronsoro, I., Rubio, L., Munoz, P., García-Palomero, E., Del Monte, M., Bidon-Chanal, A., Orozco, M., Luque, F. J., Castro, A., Medina, M. Donepezil–tacrine hybrid related derivatives as new dual binding site inhibitors of AChE. Bioorg. & Med. Chem. 2005, 13, 6588; https://doi.org/10.1016/j.bmc.2005.09.029.Suche in Google Scholar

33. Peytam, F., Adib, M., Shourgeshty, R., Firoozpour, L., Rahmanian-Jazi, M., Jahani, M., Safari, F. An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo [1, 5-a] pyrimidines with α-glucosidase inhibitory activity. Sci. Rep. 2020, 10, 1; https://doi.org/10.1038/s41598-020-59079-z.Suche in Google Scholar

Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/zkri-2020-0025).

Received: 2020-03-09
Accepted: 2020-06-19
Published Online: 2020-08-31
Published in Print: 2020-10-25

© 2020 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Graphical Synopsis
  3. Miscellaneous
  4. Wolfgang Jeitschko, 27.05.1936--05.08.2020
  5. Original papers
  6. Superstructure formation in Sc5Cu2In4
  7. Cd2 and Co2 dumbbell formation in the yttrium-rich intermetallic compounds Y14Ni3Cd3 and Y6Co2Zn
  8. Crystal structure of the synthetic analogue of iwateite, Na2BaMn(PO4)2: an X-ray powder diffraction and Raman study
  9. Layered calcium hydrogen selenite chlorides Ca(HSeO3)Cl and Ca(HSeO3)Cl(H2O), the first halides obtained in СaCl2–H2SeO3–H2O system
  10. Crystal structure of incommensurate ηʺ-Cu1.235Sn intermetallic
  11. Synthesis, properties and crystal structure of novel Copper(II) ammine complex with [Pd(CN)4]2− building blocks
  12. Water soluble biguanide salts and their 1,3,5-triazine derivatives as inhibitors of acetylcholinesterase and α-glucosidase
  13. Letter
  14. Attractive halogen···halogen interactions in crystal structure of trans-dibromogold(III) complex
https://doi.org/10.1515/zkri-2020-0025
Schlagwörter für diesen Artikel
acetylcholinesterase (AChE); biguanide; inhibitor; molecular structure; α-glucosidase; 1,3,5-triazine

Artikel in diesem Heft

  1. Frontmatter
  2. Graphical Synopsis
  3. Miscellaneous
  4. Wolfgang Jeitschko, 27.05.1936--05.08.2020
  5. Original papers
  6. Superstructure formation in Sc5Cu2In4
  7. Cd2 and Co2 dumbbell formation in the yttrium-rich intermetallic compounds Y14Ni3Cd3 and Y6Co2Zn
  8. Crystal structure of the synthetic analogue of iwateite, Na2BaMn(PO4)2: an X-ray powder diffraction and Raman study
  9. Layered calcium hydrogen selenite chlorides Ca(HSeO3)Cl and Ca(HSeO3)Cl(H2O), the first halides obtained in СaCl2–H2SeO3–H2O system
  10. Crystal structure of incommensurate ηʺ-Cu1.235Sn intermetallic
  11. Synthesis, properties and crystal structure of novel Copper(II) ammine complex with [Pd(CN)4]2− building blocks
  12. Water soluble biguanide salts and their 1,3,5-triazine derivatives as inhibitors of acetylcholinesterase and α-glucosidase
  13. Letter
  14. Attractive halogen···halogen interactions in crystal structure of trans-dibromogold(III) complex
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2025 De Gruyter Brill
Heruntergeladen am 19.10.2025 von https://www.degruyterbrill.com/document/doi/10.1515/zkri-2020-0025/html?lang=de
Button zum nach oben scrollen