The enzyme kinetic studies, DNA protection and antioxidant activities of furan/ thiophene-2-carboxamide derivatives

Abstract

Three furan and/or thiophene-2-carboxamide compounds, namely N-(furan-2-ylmethyl)thiophene-2-carboxamide (1), N-(furan-2-carbonyl)furan-2-carboxamide (2), and N-(Thiophene-2-ylmethyl)furan-2-carboxamide (3) were investigated the enzyme kinetic studies by urease, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). The inhibition constant (Ki) of Compound (CPD)3 by AChE was determined as 0.10 mM, and the Ki value by BChE was determined as 0.07 mM. In comparison, the Ki value of CPD1 by urease was determined as 0.10 mM. These CPDs were examined for antioxidant activity by the DPPH˙ scavenging method. CPD3 exhibited 98.93% DPPH scavenging activity compared to ascorbic acid, the positive control group. Furthermore, the DNA-protective activities of the compounds were investigated, and the DNA protection activity of CPD1 was observed to be 78%. The findings suggest that thiophene/furan carboxy amide-containing CPD1 and CPD3 might be exploited as potential structures for evaluating pharmaceuticals with greater potency.

Keywords

• Furan/thiophene-2-carboxamide
• acetylcholinesterase
• butyrylcholinesterase
• urease inhibition
• DNA-protective activity

References

1. Volodina, Y. L.; Tikhomirov, A. S.; Dezhenkova, L. G.; Ramonova, A. A.; Kononova, A. V.; Andreeva, D. V.; Kaluzhny, D. N.; Schols, D.; Moisenovich, M. M.; Shchekotikhin, A. E., 2021, Eur J Med Chem, 221, 113521.
2. Volodina, Y. L.; Tikhomirov, A. S.; Dezhenkova, L. G.; Ramonova, A. A.; Kononova, A. V.; Andreeva, D. V.; Kaluzhny, D. N.; Schols, D.; Moisenovich, M. M.; Shchekotikhin, A. E., 2021, Eur J Med Chem, 221, 113521.
3. Owa, T.; Nagasu, T., 2000, Expert Opin Ther Pat, 10 (11), 1725-1740.
4. Nan, X.; Wang, Q.-X.; Xing, S.-J.; Liang, Z.-G., 2023, J Enzym Inhib Med Ch, 38 (1), 2247183.
5. Mali, S. N.; Anand, A.; Zaki, M. E.; Al-Hussain, S. A.; Jawarkar, R. D.; Pandey, A.; Kuznetsov, A., 2023, Molecules, 28 (6), 2801.
6. Huang, E.; Zhang, L.; Xiao, C.; Meng, G.; Zhang, B.; Hu, J.; Wan, D. C.-C.; Meng, Q.; Jin, Z.; Hu, C., 2019, Chinese Chem Lett, 30 (12), 2157-2159.
7. Desantis, J.; Nannetti, G.; Massari, S.; Barreca, M. L.; Manfroni, G.; Cecchetti, V.; Palù, G.; Goracci, L.; Loregian, A.; Tabarrini, O., 2017, Eur J Med Chem, 138, 128-139.
8. Rollet-Labelle, E.; Grange, M.-J.; Elbim, C.; Marquetty, C.; Gougerot-Pocidalo, M.-A.; Pasquier, C., 1998, Free Radical Bio Med, 24 (4), 563-572.

9. Singh, P.; Vishwakarma, S. P.; Singh, R. L., 2014, J Sci Food Agr, 94 (12), 2497-2504.
10. Moskovitz, J.; Yim, M. B.; Chock, P. B., 2002, Arch Biochem Biophys, 397 (2), 354-359.
11. Sevgi, K.; Tepe, B.; Sarikurkcu, C., 2015, Food Chem Toxicol, 77, 12-21.
12. Cakmak, S.; Yenigun, S.; Ozen, T., 2023, J Iran Chem Soc, 20 (10), 2543-2553.
13. Zhang, L.; Mulrooney, S. B.; Leung, A. F.; Zeng, Y.; Ko, B. B.; Hausinger, R. P.; Sun, H., 2006, Biometals, 19 (5), 503-511.
14. Ellman, G. L.; Courtney, K. D.; Andres Jr, V.; Featherstone, R. M., 1961, Biochem Pharmacol, 7 (2), 88-95.
15. Wu, Z.; Shen, L.; Han, Q.; Lu, J.; Tang, H.; Xu, X.; Xu, H.; Huang, F.; Xie, J.; He, Z., 2017, Food Biophys, 12 (1), 78-87.
16. Blois, M. S., 1958, Nature, 181 (4617), 1199-1200.
17. Baiseitova, A.; Jenis, J.; Kim, J. Y.; Li, Z. P.; Park, K. H., 2021, Nat Prod Res, 35 (5), 880-883.
18. Başar, Y.; Demirtaş, İ.; Yenigün, S.; İpek, Y.; Özen, T.; Behçet, L., 2024, J Biomol Struct Dyn, 1-14.
19. Basar, Y.; Yenigun, S.; Gul, F.; Ozen, T.; Demirtas, I. A., M. Hakkı ; Temel, S., 2024, Int J Chem Techno, 8 (1), 62-71.
20. Gökçimen, S. Ş.; İpek, Y.; Behçet, L.; Demirtaş, İ.; Özen, T., 2024, J Biomol Struct Dyn, Published online: 12 Jan 2024, 1-18.
21. Başar, Y.; Yenigün, S.; İpek, Y.; Behçet, L.; Gül, F.; Özen, T.; Demirtaş, İ., 2023, J Biomol Struct Dyn, Published online.
22. Yenigün, S.; Başar, Y.; İpek, Y.; Behçet, L.; Özen, T.; Demirtaş, İ., 2024, J Biomol Struct Dyn, 42 (11), 5799-5816.
23. Afshari, M.; Rahimmalek, M.; Miroliaei, M.; Sabzalian, M. R.; Sadeghi, M.; Matkowski, A.; Szumny, A., 2024, Ind Crop Prod, 208, 117859.
24. Yenigun, S.; Basar, Y.; Gül, F.; Ipek, Y.; Gok, M.; Behcet, L.; Ozen, T.; Demirtas, I., 2024, ChemistrySelect, 9 (18), e202400919.
25. Yenigun, S.; Basar, Y.; Ipek, Y.; Gok, M.; Behcet, L.; Ozen, T.; Demirtas, I., 2024, Process Biochem, 143, 234-247.
26. Yenigün, S.; Ozen, T.; Başar, Y.; Ipek, Y.; Gök, M.; Behçet, L.; Demirtaş, İ., 2024, Curr Persp Med Aromatic Plants, 7 (1), 1-11.
27. Kareem, H. S.; Nordin, N.; Heidelberg, T.; Abdul-Aziz, A.; Ariffin, A., 2016, Molecules, 21 (2), 224.
28. Takahashi, O.; Kirikoshi, R., 2014, Comput Sci Disc, 7 (1), 015005.
29. Iqbal, A.; Khan, Z. A.; Shahzad, S. A.; Usman, M.; Khan, S. A.; Fauq, A. H.; Bari, A.; Sajid, M. A., 2018, Turkish J Chem, 42 (6), 1518-1533.
30. Valko, M.; Leibfritz, D.; Moncol, J.; Cronin, M. T.; Mazur, M.; Telser, J., 2007, The Int J Biochem Cell Bio, 39 (1), 44-84.
31. Azqueta, A.; Collins, A., 2016, Nutrients, 8 (12), 785.
32. Bekhouche, K.; Ozen, T.; Boussaha, S.; Koldas, S.; Yenigun, S.; Lassed, S.; Demirtas, I.; Benayache, F.; Benayache, S.; Zama, D., 2018, Bangladesh J Pharmacol, 13 (1).
33. Mondal, N. K.; Sorensen, E.; Hiivala, N.; Feller, E.; Griffith, B.; Wu, Z. J., 2013, Int J Med Sci, 10 (7), 883.
34. Ozen, T.; Yenigun, S.; Toka, M., 2022, Int J Chem Techno, 6 (1), 21-32.
35. Tuteja, N.; Singh, M. B.; Misra, M. K.; Bhalla, P. L.; Tuteja, R., 2001, Crit Rev Biochem Mol, 36 (4), 337-397.
36. Valko, M.; Izakovic, M.; Mazur, M.; Rhodes, C. J.; Telser, J., 2004, Mol Cell Biochem, 266 (1-2), 37-56.
37. Yenigun, S.; Ipek, Y.; Marah, S.; Demirtas, I.; Ozen, T., 2024, J Biomol Struct Dyn, 42 (2), 848-862.
38. De Almeida, S. M. V.; Lafayette, E. A.; Da Silva, L. P. B. G.; Amorim, C. A. d. C.; De Oliveira, T. B.; Ruiz, A. L. T. G.; De Carvalho, J. E.; De Moura, R. O.; Beltrão, E. I. C.; De Lima, M. D. C. A., 2015, Int J Mol Sci, 16 (6), 13023-13042.