Thiophenyl-chalcone derivatives: Synthesis, antioxidant activity, FMO energies and molecular parameters

Abstract

In this study, a series of thiophenyl-chalcones derivatives was synthesized and their DPPH and ABTS activities were evaluated. All thiophenyl-chalcones exhibited high antioxidant activity. Among them, 4e ((E)-5-(3-(4-(chlorosulfonyl)-3-hydroxyphenyl)-3-oxoprop-1-en-1-yl)thiophene-2-sulfonyl chloride) have higher ABTS activity (IC50 = 13.12 μM) than quercetin (IC50 = 15.49 μM), well-known as antioxidant agent and used as a standard. The structure-activity relationship results revealed that most of synthesized sulfonyl chloride derivatives (4a-e) have higher antioxidant activity than the sulphonamide derivatives (5a-c) and also 4d and 4e including hydroxyl group, exhibited the strongest antioxidant activity as expected. Additionally, the frontier molecular orbitals (FMOs) energies and molecular parameters of the synthesized molecules were calculated to support experimental results. The quantum chemical calculation results indicated that the strongest antioxidant compounds, in this study, had the lowest LUMO energies and the highest electronegativity, electron affinity and electrophilicity index.

Keywords

• Thiophene
• chalcone
• antioxidant activity

Tiyofenil-kalkon türevleri: Sentez, antioksidan aktivite, FMO enerjileri ve moleküler parametreler

Abstract

Bu çalışmada bir dizi tiyofenil-kalkon türevi sentezlendi ve bunların DPPH ve ABTS aktiviteleri incelendi. Tüm tiyofenil-kalkonlar yüksek antioksidan aktivite sergilemiştir. Bunlardan, 4e ((E)-5-(3-(4-(klorosülfonil)-3-hidroksifenil)-3-oksoprop-1-en-1-il)tiyofen-2-sülfonil klorür) antioksidan ajan olarak iyi bilinen ve standart olarak kullanılan quersetinden (IC50 = 13.12 μM) daha yüksek ABTS aktivitesine sahiptir. Yapı-aktivite ilişkisi sonuçları, sentezlenen sülfonil klorür türevlerinin (4a-e) sülfonamid türevlerinden (5a-c) daha yüksek antioksidan aktiviteye sahip olduğunu ve ayrıca hidroksil grubu içeren 4d ve 4e'nin beklendiği gibi en güçlü antioksidan aktiviteyi sergilediğini ortaya koymuştur. Ayrıca, deneysel sonuçları desteklemek için sentezlenen bileşiklerin sınır moleküler orbital (FMO) enerjileri ve moleküler parametreleri hesaplandı. Kuantum kimyasal hesaplama sonuçları, bu çalışmada en güçlü antioksidan bileşiklerin en düşük LUMO enerjilerine ve en yüksek elektronegatiflik, elektron afinitesi ve elektrofilik indeksine sahip olduğunu göstermiştir.

Keywords

• tiyofen
• kalkon
• antioksidant aktivite

References

1. Mccord, J. M., Human disease, free radicals, and the oxidant/antioxidant balance, Clinical Biochemistry, 26, 351-357, (1993).
2. Dai, Y., Shao, C., Piao, Y., Hu, H., Lu, K., Zhang, T., Zhang, X., Jia, S., Wang, M. and Man, S., The mechanism for cleavage of three typical glucosidic bonds induced by hydroxyl free radical, Carbohydrate Polymers, 178, 34-40, (2017).
3. Oberley, L. W., Free radicals and diabetes, Free Radical Biology and Medicine, 5, 113-124, (1988).
4. Fang, Y. Z., Sheng, Y. and Guoyao, W., Free radicals, antioxidants, and nutrition, Nutrition, 18, 872-879, (2002).
5. Moskovitz, J., Moon, B. Y. and Chock, P. B., Free radicals and disease, Archives of Biochemistry and Biophysics, 397, 354-359, (2002).
6. Jensen, S. J. K., Oxidative stress and free radicals, Journal of Molecular Structure: THEOCHEM, 666-667, 387-392, (2003).
7. Hayes, J. D., Dinkova-Kostova, A.T. and Tew, K. D., Oxidative stress in cancer, Cancer Cells, 38, 167-197, (2020).
8. Pisoschi, A. M., Pop, A., Iordache, F., Stanca, L., Predoi, G. and Serban, A. I., Oxidative stress mitigation by antioxidants-an overview on their chemistry and influences on health status, European Journal of Medicinal Chemistry, 209, 112891, (2021).

9. Sies, H. and Jones, D. P., Reactive oxygen species (ROS) as pleiotropic physiological signalling agents, Nature Reviews Molecular Cell Biology, 21, 363-383, (2020).
10. Zhang, N., Hu, P., Wang, Y., Tang, Q., Zheng, Q., Wang, Z. and He, Y., A reactive oxygen species (ROS) activated hydrogen sulfide (H2S) donor with self-reporting fluorescence, ACS Sensors, 5, 319-326, (2020).
11. Irazabal, M. V. and Torres, V. E., Reactive oxygen species and redox signaling in chronic kidney disease, Cells, 9, 1342, (2020).
12. Kirtonia, A., Sethi, G. and Garg, M., The multifaceted role of reactive oxygen species in tumorigenesis, Cellular and Molecular Life Sciences,77, 4459–4483, (2020).
13. Kurt, B. Z., Gazioglu, I., Kandas, N. O. and Sonmez, F., Synthesis, anticholinesterase, antioxidant, and anti-aflatoxigenic activity of novel coumarin carbamate derivatives, ChemistrySelect, 3, 3978–3983, (2018).
14. Kahriman, N., Yeni 3,5-disübstitüe-2-pirazolin türevlerinin sentezi ve biyolojik aktivitelerinin incelenmesi, Journal of Balıkesir University Institute of Science and Technology, 22, 1, 34-47, (2020).
15. Sahu, N., Balbhadra, S., Choudhary, J. and Kohli, D., Exploring pharmacological significance of chalcone scaffold: a review, Current Medicinal Chemistry,19, 209-225, (2012).
16. Gaonkar, S. L. and Vignesh, U. N., Synthesis and pharmacological properties of chalcones: a review, Research on Chemical Intermediates, 43, 6043-6077, (2017).
17. Singh, P., Anand, A. and Kumar, V., Recent developments in biological activities of chalcones: A mini review, European Journal of Medicinal Chemistry, 85, 758-777, (2014).
18. Sonmez, F., Sevmezler, S., Atahan, A., Ceylan, M., Demir, D., Gencer, N., Arslan, O. and Kucukislamoglu, M., Evaluation of new chalcone derivatives as polyphenol oxidase inhibitors, Bioorganic and Medicinal Chemistry Letters, 21, 7479–7482, (2011).
19. Dan, W. and Dai, J., Recent developments of chalcones as potential antibacterial agents in medicinal chemistry, European Journal of Medicinal Chemistry, 187, 111980, (2020).
20. Rani, A., Anand, A., Kumar, K. and Kumar, V., Recent developments in biological aspects of chalcones: the odyssey continues, Expert Opinion Drug Discovery, 14, 249-288, (2019).
21. Dandawate, P., Ahmed, K., Padhye, S., Ahmad, A. and Biersack, B., Anticancer active heterocyclic chalcones: recent developments, Anti-Cancer Agents in Medicinal Chemistry, 21, 558-566, (2021).
22. Basappa V. C., Ramaiah, S., Penubolu, S. and Kariyappa, A. K., Recent developments on the synthetic and biological applications of chalcones-A review, Biointerface Research in Applied Chemistry, 12, 180-195, (2021).
23. Salotra, R. and Utreja, D., A comprehensive appraisal of chalcones and their heterocyclic analogs as antimicrobial agents, Current Organic Chemistry, 24, 2755-2781, (2020).
24. Kesari, C., Rama, K. R., Sedighi, K., Stenvang, J., Björkling, F., Kankala, S. and Thota, N., Synthesis of thiazole linked chalcones and their pyrimidine analogues as anticancer agents, Synthetic Communications, 51, 1406-1416, (2021).
25. Gür, T., Tiyofenilşalkon Türevlerinin Sentezi, Yüksek Lisans Tezi, Sakarya Üniversitesi, Fen Bilimleri Enstitüsü, Sakarya, (2019).
26. Sonmez, F., Gunesli, Z., Kurt, B. Z., Gazioglu, I., Avci, D. and Kucukislamoglu, M., Molecular Diversity, 23, 829–844, (2019).
27. Yakan, H., Cavus, M. S., Kurt, B. Z., Muglu, H., Sonmez, F. and Güzel, E., Journal of Molecular Structure, 1239, 130495, (2021).
28. Shao, Y., Gan, Z., Epifanovsky, E., Gilbert, A.T.B., Wormit, M., Kussmann, J., Lange, A. W., Behn, A., Deng, J., Feng, X., Ghosh, D., Goldey, M., Horn, P.R., Jacobson, L. D., Kaliman, I., Khaliullin, R.Z., Kús, T., Landau, A., Liu, J., Proynov, E.I., Rhee, Y. M., Richard, R.M., Rohrdanz, M.A., Steele, R.P., Sundstrom, E.J., Woodcock, H. L., Zimmerman, P.M., Zuev, D., Albrecht, B., Alguire, E., Austin, B., and Chen, Y., Q-Chem 4.3, Pleasanton, CA, (2015).
29. Shao, Y. H., Gan, Z. T., Epifanovsky, E., Gilbert, A. T. B., Wormit, M., Kussmann, J., Lange, A. W., Behn, A., Deng, J. and Feng, X. T., Advances in molecular quantum chemistry contained in the Q-Chem 4 program package, Molecular Physics, 113, 184–215, (2015).
30. Tao, J., Perdew, J. P., Staroverov, V. N. and Scuseria, G. E., Climbing the density functional ladder: Nonempirical meta–generalized gradient approximation designed for molecules and solids, Physical Review Letters, 91, 146401, (2003).
31. Liu, F., Proynov, E., Yu, J. G., Furlani, T. R. and Kong, J., Comparison of the performance of exact-exchange-based density functional methods, Journal of Chemical Physics, 137, 114104, (2012).
32. Chattaraj, P. K. and Roy, D.R., Update 1 of: Electrophilicity index, Chemical Reviews, 107, 46-74, (2007).
33. Eryılmaz, S., Gül, M. and Inkaya, E., Synthesis, spectral characterization, theoretical analysis and antioxidant activities of aldol derivative isophorone structures, Journal of Balıkesir University Institute of Science and Technology, 19, 3, 89-104, (2017).
34. Dege, N., Ozge, O., Avci, D., Basoglu, A., Sonmez, F., Yaman, M., Tamer, O., Atalay, Y. and Kurt, B. Z., Concentration effects on optical properties, DFT, crystal characterization and α-glucosidase activity studies: Novel Zn(II) complex, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 262, 120072, (2021).
35. Muğlu, H., Kurt, B. Z., Sönmez, F., Güzel, E., Çavuş, M. S. and Yakan, H., Preparation, antioxidant activity, and theoretical studies on the relationship between antioxidant and electronic properties of bis(thio/carbohydrazone) derivatives, Journal of Physics and Chemistry of Solids, 164, 110618, (2022).
36. Gazioglu, I., Kurt, B. Z., Sevgi, E. and Sonmez, F., Anticholinesterase, antioxidant, antiaflatoxigenic activities of ten edible wild plants from Ordu area, Turkey, Iranian Journal of Pharmaceutical Research, 17, 1047-1056, (2018).
37. Belkheiri, N., Bouguerne, B., Bedos-Belval, F., Duran, H., Bernis, C., Salvayre, R., Negre-Salvayre, A. and Baltas, M., Synthesis and antioxidant activity evaluation of a syringic hydrazones family, European Journal of Medicinal Chemistry, 45, 3019-3026, (2010).
38. Campos, A. M. and Lissi, E. A., Kinetics of the reaction between 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) derived radical cations and phenols, International Journal of Chemical Kinetics, 29, 219-224, (1997).
39. Herraiz, T. and Galisteo, J., Endogenous and dietary indoles: A class of antioxidants and radical scavengers in the ABTS assay, Free Radical Research, 38, 323-331, (2004).
40. Powis, G., Free radical formation by antitumor quinones, Advances in Free Radical Biology and Medicine, 6, 63-101, (1989).
41. Soares, M. A., Lessa, J. A., Mendes, I. C., Da Silva, J. G., dos Santos, R. G., Salum, L. B., Daghestani, H., Andricopulo, A. D., Day, B. W., Vogt, A., Pesquero, J. L., Rocha, W. R. and Beraldo, H., N4-Phenyl-substituted 2-acetylpyridine thiosemicarbazones: Cytotoxicity against human tumor cells, structure–activity relationship studies and investigation on the mechanism of action, Bioorganic and Medicinal Chemistry, 20, 3396-3409, (2012).