Resorcinol derivatives as human acetylcholinesterase inhibitor: An In Vitro and In Silico study

Abstract

Inhibitors of Acetylcholinesterase (Acetylcholine acetylhydrolase, AChE, E.C.3.1.1.7) are highly significant in the treatment of neurodegenerative diseases such as Alzheimer’s disease (AD) due to the deep relationship with memory and acetylcholine. So investigation of natural AChE inhibitors having minimal side effects has become important. In this paper human erythrocytes AChE enzyme (0.032 EU mg-1 protein) was partially isolated by using DE-52 anion exchange chromatography. Then, primer effects of resorcinol derivatives on the enzyme activity were studied and IC50 values were found in the range of 2.74-363.61 µM. Besides, inhibition profiles were elucidated by molecular docking and the highest inhibition potency was observed in 4-hexylresorcinol with the free binding energy of -6.16 kcal mol-1. In conclusion, by using both in vitro and in silico approaches it was found that 4-hexylresorcinol had the highest inhibitory potential on human AChE. So, this compound may be used in drug design in memory-lost diseases.

Keywords

• Acetylcholinesterase
• resorcinol
• inhibition
• molecular docking

References

1. Blennow, K.; de Leon, M. J.; Zetterberg, H. Lancet (London, England) 2006, 368 (9533), 387-403.
2. Burns, A.; Iliffe, S. BMJ (Clinical researched) 2009, 338:b158.
3. Reitz, C.; Mayeux, R. Biochemical pharmacology 2014, 88 (4), 640-651.
4. Baptista, F. I.; Henriques, A. G.; Silva, A. M.; Wiltfang, J.; da Cruz e Silva, O. A. ACS chemical neuroscience 2014, 5 (2), 83-92.
5. Du, X.; Wang, X.; Geng, M. Translational neurodegeneration 2018, 7 (1), 1-7.
6. Hardy, J.; Selkoe, D. J. science 2002, 297 (5580), 353-356.
7. Tang, B. L.; Kumar, R. Ann Acad Med Singapore 2008, 37 (5), 406-5.
8. Coyle, J. T.; Price, D. L.; Delong, M. R. Science 1983, 219 (4589), 1184-1190.

9. Blokland, A., Brain Research Reviews 1995, 21 (3), 285-300.
10. Francis, P. T.; Palmer, A. M.; Snape, M.; Wilcock, G. K. Journal of Neurology, Neurosurgery & Psychiatry 1999, 66 (2), 137-147.
11. H Ferreira-Vieira, T.; M Guimaraes, I.; R Silva, F.; M Ribeiro, F. Current neuropharmacology 2016, 14 (1), 101-115.
12. Pope, C. N.; Brimijoin, S. Biochemical pharmacology 2018, 153, 205-216.
13. Greig, N. H.; Utsuki, T.; Yu, Q.-s.; Zhu, X.; Holloway, H. W.; Perry, T.; Lee, B.; Ingram, D. K.; Lahiri, D. K. Current medical research and opinion 2001, 17 (3), 159-165.
14. Ahmad, B.; Mukarram Shah, S.; Khan, H.; Hassan Shah, S. Journal of enzyme inhibition and medicinal chemistry 2007, 22 (6), 730-732.
15. Colovic, M. B.; Krstic, D. Z.; Lazarevic-Pasti, T. D.; Bondzic, A. M.; Vasic, V. M. Current neuropharmacology 2013, 11 (3), 315-335.
16. Sun, Y.; Lai, M. S.; Lu, C. J.; Chen, R. C. European journal of neurology 2008, 15 (3), 278-283.
17. Kozubek, A.; Tyman, J. H. P. Chem Rev 1999, 99 (1), 1-25.
18. Srimai, V.; Ramesh, M.; Parameshwar, K. S.; Parthasarathy, T. Medicinal Chemistry Research 2013, 22 (11), 5314-5323.
19. Worek, F.; Mast, U.; Kiderlen, D.; Diepold, C.; Eyer, P. Clinica Chimica Acta 1999, 288 (1-2), 73-90.
20. Bradford, M. M. Anal Biochem 1976, 72 (1-2), 248-254.
21. Guller, U.; Guller, P.; Ciftci, M. Altern Ther Health Med 2020.
22. Adem, S.; Akkemik, E.; Aksit, H.; Guller, P.; Tufekci, A. R.; Demirtas, I.; Ciftci, M. Medicinal Chemistry Research 2019, 28 (5), 711-722.
23. Cheung, J.; Rudolph, M. J.; Burshteyn, F.; Cassidy, M. S.; Gary, E. N.; Love, J.; Franklin, M. C.; Height, J. J. Journal of medicinal chemistry 2012, 55 (22), 10282-10286.
24. Morris, G. M.; Huey, R.; Lindstrom, W.; Sanner, M. F.; Belew, R. K.; Goodsell, D. S.; Olson, A. J, J Comput Chem 2009, 30 (16), 2785-2791.
25. Geula, C.; Mesulam, M. M. Cholinergic Systems in Alzheimer’s Disease, Alzheimer Disease. 2 ed.; Lippincott, Williams and Wilkins: Philadelphia, PA, 1999.
26. Dhanasekaran, S.; Perumal, P.; Palayan, M. Journal of Applied Pharmaceutical Science 2015, 5 (02), 012-016.
27. Forette, F. B. Alzheimer Hastalığında İlaç Geliştirilmesi: Tarihçesine Bakış ve Geleceğine İlişkin Öngörüler. In Alzheimer Hastalığının Farmakoterapisi, Gauthier, S., Ed. Yelkovan Yayıncılık: İstanbul, 2000; pp 1-5.
28. Bores, G. M.; Huger, F. P.; Petko, W.; Mutlib, A. E.; Camacho, F.; Rush, D. K.; Selk, D. E.; Wolf, V.; Kosley, R.; Davis, L. Journal of Pharmacology and Experimental Therapeutics 1996, 277 (2), 728-738.
29. Giacobini, E. Cholinesterase Inhibitors. In Enzymes of the cholinesterase family, Springer: 1995; pp 463-469.
30. Abbasi, M. A.; Hassan, M.; Siddiqui, S. Z.; Shah, S. A. A.; Raza, H.; Seo, S. Y. PeerJ 2018, 6, e4962.
31. Biscussi, B.; Sequeira, M. A.; Richmond, V.; Mañez, P. A.; Murray, A. P. Journal of Photochemistry and Photobiology A: Chemistry 2021, 113375.
32. Song, M.-q.; Min, W.; Wang, J.; Si, X.-X.; Wang, X.-J.; Liu, Y.-W.; Shi, D.-H. Journal of Molecular Structure 2021, 1229, 129784.
33. Zhao, Y.; Ye, F.; Xu, J.; Liao, Q.; Chen, L.; Zhang, W.; Sun, H.; Liu, W.; Feng, F.; Qu, W. Bioorganic & medicinal chemistry 2018, 26 (13), 3812-3824.
34. Lopes, J. P. B.; Silva, L.; da Costa Franarin, G.; Ceschi, M. A.; Lüdtke, D. S.; Dantas, R. F.; de Salles, C. M. C.; Silva-Jr, F. P.; Senger, M. R.; Guedes, I. A. Bioorganic & medicinal chemistry 2018, 26 (20), 5566-5577.
35. Krátký, M.; Štěpánková, Š.; Vorčáková, K.; Vinšová, J. Bioorganic chemistry 2018, 80, 668-673.
36. Guevara, J. A.; Trujillo, J. G.; Quintana, D.; Jiménez, H. A.; Arellano, M. G.; Bahena, J. R.; Tamay, F.; Ciprés, F. J. Medicinal Chemistry Research 2018, 27 (3), 989-1003.
37. Kurt, B. Z.; Gazioglu, I.; Kandas, N. O.; Sonmez, F. ChemistrySelect 2018, 3 (14), 3978-3983.
38. Güller, P.; Dağalan, Z.; Güller, U.; Çalışır, U.; Nişancı, B. Journal of Molecular Structure 2021, 1239, 130498.
39. Valencia, M. E.; Herrera-Arozamena, C.; de Andrés, L.; Pérez, C.; Morales-García, J. A.; Pérez-Castillo, A.; Ramos, E.; Romero, A.; Viña, D.; Yáñez, M. European journal of medicinal chemistry 2018, 156, 534-553.
40. Güller, P. Journal of Molecular Structure 2021, 1228, 129790.
41. Zhang, X.-Z.; Xu, Y.; Jian, M.-M.; Yang, K.; Ma, Z.-Y. Medicinal Chemistry Research 2019, 28 (10), 1683-1693.
42. Fernandes, T. B.; Cunha, M. R.; Sakata, R. P.; Candido, T. M.; Baby, A. R.; Tavares, M. T.; Barbosa, E. G.; Almeida, W. P.; Parise‐Filho, R. Archiv der Pharmazie 2017, 350 (11), 1700163.