Synthesis, Characterization and Radical Scavenging Activities of 1,3-Disubstituted Benzimidazolium Salts

Serpil Demir Düşünceli; Buket Karatepe; Serhat Keser

doi:10.54565/jphcfum.1712592

Synthesis, Characterization and Radical Scavenging Activities of 1,3-Disubstituted Benzimidazolium Salts

Abstract

The reaction of N-substituted benzimidazole and alkyl halides (benzyl bromoacetate and trifluoromethoxybenzyl bromide) gave a series of 1,3-disubstituted benzimidazolium salts. The structure of synthesized compounds was confirmed by various spectroscopic techniques such as 1H, 13C and 19F NMR spectroscopy, FT-IR and elemental analysis. Biological efficiency of these compounds was evaluated by antioxidant activities like ABTS, OH and DPPH radical scavenging activity.

Keywords

Supporting Institution

İnonu University

Project Number

FLO-2024-3506

Ethical Statement

not necessary

Thanks

The research is financially supported by the İnönü University Research Fund (İ.Ü. B.A.P. Project No: FLO-2024-3506).

References

[1] Pizzino, G., Irrera, N., Cucinotta, M., Pallio, G., Mannino, F., Arcoraci, V., Squadrito, F., Altavilla, D., Bitto, A., 2017. Oxidative Stress: Harms and Benefits for Human Health, Oxid. Med. Cell Longev. 1, 1-13.
[2] Rajendran, P., Nandakumar, N., Rengarajan, T., Palaniswami R., Gnanadhas, E. N., Lakshminarasaiah, U., Gopas, J., Nishigaki, I., 2014. Antioxidants and human diseases, Clinica Chimica Acta 436, 332-347.
[3] Wu, J. Q., Kosten, T. R., Zhang, X. Y., 2013. Free radicals, antioxidant defense system, and schizophrenia, Prog. Neuro-Psychopharmacol. Biol. Psychiatry 46, 200-206.
[4] Taniyama, Y., Griendling, K. K., 2003. Reactive oxygen species in the vasculature, Hyper-tension 42, 1075-1081.
[5] Al-Gubory, K. H., Garrel, C., Faure, P., Sugino,N., 2012. Roles of antioxidant enzymes in corpus luteum rescue from reactive oxygen species-induced oxidative stress, Reproductive Biomedicine Online 25, 551-560.
[6] Saffrané, L. M., DellaPenna, D., 2010. Biosynthesis, regulation and functions of tocochromanols in plants, Plant Physiol. Biochem. 48, 301-309.
[7] Pandey, A. K., 2007. Anti-staphylococcal activity of a pan-tropical aggressive and ob-noxious weed Pariheniumhisterophorus: an in vitro study, Natl. Acad. Sci. Lett. 30, 383-386.
[8] Carr, A., Frei, B., 1999. Does vitamin C act as pro-oxidant under physiological conditions?, FASEB Journal 13, 1007-1024 .

[9] Prochazkova, D., Bousova, I., Wilhelmova, N., 2011. Antioxidant and prooxidant properties of flavonoids, Fitoterapia 82, 513-523.
[10] Alagöz, Z. A., Buyukbingol, I., 2001. Synthesis of some novel tetrahydronaphthalene benzimidazole derivatives, Heterocycl Commun. 7, 455-460.
[11] Alagöz, Z. A., Kuş, C., Çoban, T., 2005. Synthesis and antioxidant properties of novel benzimidazoles containing substituted indole or 1,1,4,4-tetramethyl1,2,3,4-tetrahydro-naphthalene fragments,” J. Enzy. Inhib. Med. Chem. 20:4, 325-331.
[12] Kılcıgil, G. A., Kuş, C., Özdamar, E. D., Eke, B. C., İşcan, M., 2007. Synthesis and Antioxidant Capacities of Some New Benzimidazole Derivatives, Arch Pharm Chem. Life Sci. 340, 607-611.
[13] Kuş¸ C., Kılcıgil, G. A., Eke, B C., İşcan, M., 2004. Synthesis and antioxidant properties of some novel benzimidazole derivatives on lipid peroxidation in the rat liver,” Arch Pharm Res. 27, 156-163.
[14] Elimam, D. M., Elgazar, A. A., El-Senduny, F. F., El-Domany, R. A., Badria, F. A., Eldehna, W. M., 2022. Natural inspired piperine-based ureas and amides as novel antitumor agents towards breast cancer, J. Enzyme Inhib. Med. Chem. 37, 39-50.
[15] Ozkay, Y., Tunali, Y., Karaca, H., Işıkdağ, İ., 2010. Antimicrobial activity and a SAR study of some novel benzimidazole derivatives bearing hydrazone moiety, Eur. J. Med. Chem. 45, 3293-3298.
[16] Sreena, K., Ratheesh, R., Rachana, M., Poornima, M., Shyni, C., 2009. Synthesis and anthelmintic activity of benzimidazole derivatives, Hygeia 1, 21-22 .
[17] Matiadis, D., Sagnou, M., 2020. Pyrazoline hybrids as promising anticancer agents: an up-to-date overview, Int. J. Mol. Sci. 21 (2020): 5507.
[18] Lien, J. C., Chung, C.-L., Huang, T.‐F., Chang, T.‐C., Chen, K.‐C., Gao, G.‐Y., Hsu, M.‐J., Huang, S. W., 2019. A novel 2-aminobenzimidazole-based compound Jzu 17 exhibits anti-angiogenesis effects by targeting VEGFR-2 signalling, Br. J. Pharmacol. 176, 4034-4049.
[19] Kusanur, R. A, Kulkarni, M. W., 2014. A novel route for the synthesis of recemic 4-(coumaryl) alanines and their antimicrobial activity, Asian J. Chem. 4, 1077-1080.
[20] Akhtar, M. J., Yar, M. S., Sharma, V. K., Khan, A. A., Ali, Z., Haider, M. R., Pathak, A., 2020. Recent progress of benzimidazole hybrids for anticancer potential, Curr. Med. Chem. 27, 5970-6014.
[21] Haque, R. A., Iqbal, M. A., Asekunowo, P., Majid, A.M.S.A., Ahamed, M.B.K., Umar, M. I., Al-Rawi, S. S., Al-Suede, F. S. R., 2013. Synthesis, structure, anticancer, and antioxidant activity of para-xylyl linked bis-benzimidazolium salts and respective dinuclear Ag(I) N-heterocyclic carbene complexes (Part-II), Med. Chem. Res. 22, 4663-4676.
[22] Bal, S., Demirci, Ö., Şen, B., Taslimi, P., Aktaş, A., Gök, Y., Aygün, M., Gülçin, İ., 2021. Synthesis, characterization, crystal structure, α-glycosidase, and acetylcholinesterase inhibitory properties of 1,3-disubstituted benzimidazolium salts, Arch. Pharm. 354,: e2000422.
[23] Kazancı, A., Gök, Y., Kaya, R., Aktaş, A., Taslimi, P., Gülçin,İ., 2021. Synthesis, characterization and bioactivities of dative donor ligand N-heterocyclic carbene (NHC) precursors and their Ag(I)NHC coordination compounds, Polyhedron 193, 114866.
[24] Atyam, V. S.S.S.G., Raidu, C. S., Nannapaneni, D. T., Reddy, M. I., 2010. Synthesis, characterization, and biological evaluation of benzimidazole derivatives as potential anxiolytics, J. Young Pharm. 2, 273-279.
[25] Meanwell, N. A., 2018. Fluorine and fluorinated motifs in the design and application of bioisosteres for drug design, J. Med. Chem., 61, 5822-5880.
[26] Gillis, E. P., Eastman, K. J., Hill, M. D., Donnelly, D. J., Meanwell, N. A., 2015. Applications of fluorine in medicinal chemistry, J. Med. Chem., 58, 8315-8359.
[27] Gök, Y., Kaya, G., Demir,Y., Karabıyık, H., Tok, T. T., M. İzmirli, Aktaş, A., Gülçin, İ., 2025. Benzimidazolium salts bearing ester group: Synthesis characterization, crystal structure, molecular docking studies, and inhibitory properties against metabolic enzymes, J.Mol.Struc. 1322, 140342.
[28] Sheppard, W. A., 1964. α-Fluorinated ethers. I. Aryl fluoroalkyl ethers1, J. Org. Chem. 29, 1-11.
[29] Aldrich, P.E., Sheppard, W. A., 1964. α-Fluorinated ethers. II. Alkyl fluoroalkyl ethers1 , J. Org. Chem. 29, 11-15.
[30] Muniz, S.C., Anthony, R., Niemann, S., Alffenear, J. W. C., 2017. “New approaches and therapeutic options for mycobacterium tuberculosis in a dormant state, Clin. Microbiol. Rev. 31, 1-13.
[31] Skripconoka, V., Danilovits, M., Pehme, L., Tomson, T., Skenders, G., Kummik, T., Cirule, A., Leimane, V., Kurve, A., Levina, K., Geiter, L. J., Manissereo, D., Wells, C. D., 2013. Delamanid improves outcomes and reduces mortality in multidrugresistant tuberculosis, Eur. Respir. J. 41, 1393-1400.
[32] Mathew, S. J., Manji, H. K., Charney, D. S., 2008. Novel drugs and therapeutic targets for severe mood disorders, Neuropsychopharmacology 33, 2080-2092.
[33] Blumberg, D., Doron, S., Bitton, S., 1985. Effect of triflumuron on two species of nitidulid beetles, Carpophilus hemipterus and Urophorus humeralis, Phytoparasitica 13, 9-19.
[34] Chen, Y., Zhang, A. F., Wang, W. X., Zhang Y., Gao, T. C., 2012. Baseline sensitivity and efficacy of thifluzamide in Rhizoctonia solani, Ann. Appl. Biol. 161, 247-254.
[35] Whipker, B. E., McCall, I., Gibson, J. L., Cavins, T. J., 2002, Efficacy of flurprimidol (Topflor) on bedding plants, Acta Hortic. 624, 413-418.
[36] Cueva, C., Arribas,M. V. M., Alvarez, P. J. M., Bills, G., Vicente, M. F., Basilio, A., Rivas, C. L., Requena, T., Rodrıguez, J. M., Bartolome, B., 2010. Antimicrobial activity of phenolic acids against commensal, probiotic and pathogenic bacteria, Res. Microbiol. 161, 372-382.
[37] Chong, K. P., Rossall,S., Atong, M., 2009. In vitro antimicrobial activity and fungitoxicity of syringic acid, cafeic acid and 4-hydroxybenzoic acid against Ganoderma Boninense,” J. Agric. Sci. 1, 15-20.
[38] Kosová, M., Hrádková, I., Mátlová, V., Kadlec, D., Smidrkal, J., Filip, V., 2015. Antimicrobial efect of 4-hydroxybenzoic acid ester with glycerol, J. Clin. Pharm. Ther. 40, 436-440.
[39] Özçelik, H., Kartal, M., Orhan, I., 2011. Cytotoxicity, antiviral and antimicrobial activities of alkaloids, favonoids, and phenolic acids, Pharm. Biol. 49, 396-402.
[40] Flausino, O. A., Dufau, L., Regasini, L. O., Petronio, M. S., Silva, D. H. S., Rose, T., Bolzani, V. S., Ravaux, M. R., 2012. Alkyl hydroxybenzoic acid derivatives that inhibit HIV-1 protease dimerization, Curr. Med. Chem. 19, 4534-4540.
[41] Manuja, R., Sachdeva, S., Jain, A., Chaudhary, J., 2013. A comprehensive review on biological activities of P-hydroxy benzoic acid and its derivatives, Int. J. Pharm. Sci. Rev. Res. 22, 109-115.
[42] Patchett, A. A., 1984. The chemistry of enalapril, Br. J. Clin. Pharmacol. 18, 201S–207S.
[43] Hamide, M. Gök, Y., Demir, Y., Sevinçek, R., Tok, T. T., Tezcan, B., Aktaş, A., Gülçin, İ., Aygün, M. Güzel,B., 2022. Benzimidazolium salts containing trifluoromethoxybezyl: synthesis characterization, crystal structure, molecular docking studies and enzymes inhibitory properties, Chem. Biodiversity. 19, e202200257.
[44] Keser, S., Keser, F., Karatepe, M., Kaygili, O., Tekin, S., Turkoglu, I., Demir, E., Yilmaz, O., Kirbag, S., Sandal, S., 2020. Bioactive contents, in vitro antiradical, antimicrobial and cytotoxic properties of rhubarb (Rheum ribes L.) extracts, Natur. Product Res. 34, 3353-3357.
[45] Keser, S., Kak, O., 2021. In vitro antimicrobial, antiradical, anticancer evaluation, and phytochemical contents of endemic Scorzonera semicana DC, J. Food Process. Pres. 45, e15971.
[46] Shimada, K., Fujikawa, K., Yahara, K., Nakamura, T., 1992. Antioxidant properties of xanthin on autoxidation of soybean oil in cyclodextrin emulsion, J. Agricultur. Food Chem. 40, 945-948.
[47] Yu, L., Haley, S., Perret, J., Harris, M., Wilson, J., Qıan, M., 2002. Free radical scavenging properties of wheat extracts, J. Agricultur. Food Chem. 50, 1619-1624.
[48] Halliwell, B., Gutteridge, J. M. C., Aruoma, O., 1987. The deoxyribose method: a simple “test tube” assay for determination of rate constants for reactions of hydroxyl radicals, Analytic. Biochem. 165, 215-219.
[49] Ebenezer, O., Joshua, F. O., Omotoso, O. D., Shapi, M., 2022. Benzimidazole and its derivatives: Recent Advances (2020–2022), Results in Chem. 5, 100925.
[50] El Ouasif, L., Bouyahya, A., Zniber, R., Ghoul, M., Achour, R., Chakchak, H., Talbaoui, A., Boury, H., Dakka, N., Bakri, Y., 2017. Novel 2-mercaptobenzimidazole derivatives: synthesis and evaluation of their antibacterial and antioxidant activities,” Mediterr. J. Chem. 6(3), 77-87.
[51] Argirova, M. A., Georgieva, M. K., Avakumova, N. G. H., Vuchev, D. I., Daskalova, G. V. P., Anichina, K. K. Yancheva, D. Y., 2021. New 1H-benzimidazole-2-yl hydrazones with combined antiparasitic and antioxidant activity, RSC Adv. 11, 39848-39868.
[52] Khodja, I. A., Bensouici, C., Bouleb, H., 2020. Combined experimental and theoretical studies of the structure antiradical activity relationship of heterocyclic hydrazone compounds, J. Mol. Struct. 1221, 128858.
[53] Shatokhin, S. S., Tuskaev, V. A., Gagieva, S. C., Markova, A. A., Pozdnyakov, D. I., Melnikova, E. K., Bulychev, B. M., Oganesyan, E. T., 2022. Synthesis, cytotoxic and antioxidant activities of new n-substituted 3-(benzimidazol-2-yl)-chromones containing 2,6-di-tert-butylphenol fragment, J. Mol. Struct. 1249, 131683.
[54] Prakash, S., Somiya, G., Elavarasan, N., Subashini, K., Kanaga, S., Dhandapani, R., Sivanandam, M., Kumaradhas, P., Thirunavukkarasu, C., Sujatha, V., 2021. Synthesis and characterization of novel bioactive azo compounds fused with benzothiazole and their versatile biological applications, J. Mol. Struct. 1224, 129016.

Details

Primary Language

English

Subjects

Biochemistry and Cell Biology (Other)

Journal Section

Research Article

Authors

Serpil Demir Düşünceli ^*
0000-0001-8765-4039
Türkiye

Buket Karatepe
0000-0000-0000-0000
Türkiye

Serhat Keser
0000-0002-9678-1053
Türkiye

Publication Date

June 17, 2025

Submission Date

June 2, 2025

Acceptance Date

June 10, 2025

Published in Issue

Year 2025 Volume: 8 Number: 1

DOI

https://doi.org/10.54565/jphcfum.1712592

IZ

https://izlik.org/JA82GL36SE

Cite

RIS / Bibtex

APA

Demir Düşünceli, S., Karatepe, B., & Keser, S. (2025). Synthesis, Characterization and Radical Scavenging Activities of 1,3-Disubstituted Benzimidazolium Salts. Journal of Physical Chemistry and Functional Materials, 8(1), 91-102. https://doi.org/10.54565/jphcfum.1712592

AMA

1.Demir Düşünceli S, Karatepe B, Keser S. Synthesis, Characterization and Radical Scavenging Activities of 1,3-Disubstituted Benzimidazolium Salts. Journal of Physical Chemistry and Functional Materials. 2025;8(1):91-102. doi:10.54565/jphcfum.1712592

Chicago

Demir Düşünceli, Serpil, Buket Karatepe, and Serhat Keser. 2025. “Synthesis, Characterization and Radical Scavenging Activities of 1,3-Disubstituted Benzimidazolium Salts”. Journal of Physical Chemistry and Functional Materials 8 (1): 91-102. https://doi.org/10.54565/jphcfum.1712592.

EndNote

Demir Düşünceli S, Karatepe B, Keser S (June 1, 2025) Synthesis, Characterization and Radical Scavenging Activities of 1,3-Disubstituted Benzimidazolium Salts. Journal of Physical Chemistry and Functional Materials 8 1 91–102.

IEEE

[1]S. Demir Düşünceli, B. Karatepe, and S. Keser, “Synthesis, Characterization and Radical Scavenging Activities of 1,3-Disubstituted Benzimidazolium Salts”, Journal of Physical Chemistry and Functional Materials, vol. 8, no. 1, pp. 91–102, June 2025, doi: 10.54565/jphcfum.1712592.

ISNAD

Demir Düşünceli, Serpil - Karatepe, Buket - Keser, Serhat. “Synthesis, Characterization and Radical Scavenging Activities of 1,3-Disubstituted Benzimidazolium Salts”. Journal of Physical Chemistry and Functional Materials 8/1 (June 1, 2025): 91-102. https://doi.org/10.54565/jphcfum.1712592.

JAMA

1.Demir Düşünceli S, Karatepe B, Keser S. Synthesis, Characterization and Radical Scavenging Activities of 1,3-Disubstituted Benzimidazolium Salts. Journal of Physical Chemistry and Functional Materials. 2025;8:91–102.

MLA

Demir Düşünceli, Serpil, et al. “Synthesis, Characterization and Radical Scavenging Activities of 1,3-Disubstituted Benzimidazolium Salts”. Journal of Physical Chemistry and Functional Materials, vol. 8, no. 1, June 2025, pp. 91-102, doi:10.54565/jphcfum.1712592.

Vancouver

1.Serpil Demir Düşünceli, Buket Karatepe, Serhat Keser. Synthesis, Characterization and Radical Scavenging Activities of 1,3-Disubstituted Benzimidazolium Salts. Journal of Physical Chemistry and Functional Materials. 2025 Jun. 1;8(1):91-102. doi:10.54565/jphcfum.1712592