Yeni Benzimidazol Bileşiklerinin Sentezi, Antioksidan ve Antiüreaz Aktiviteleri

Year 2023, Volume: 2 Issue: 2, 60 - 76, 31.07.2023

Hakan Akgün , Taner İlker Gümrükçüoğlu , Hakan Bektaş , Bahar Bilgin Sökmen

https://doi.org/10.59312/ebshealth.1326437

Cited By: 1

Abstract

Bu çalışmada, yeni bir seri benzimidazol türevi (1-5) sentezlenerek antioksidan ve antiüreaz aktiviteleri spektrofotometrik metotlarla incelendi. Sentezlenen yeni benzimidazol bileşiklerinin antioksidan aktiviteleri, DPPH (1,1-difenil-2-pikrilhidrazil) serbest radikal süpürme aktivitesi, ABTS (2,2'-azino-bis(3-etilbenzotiazolin-6-sülfonik asit) diamonyum tuzu) radikal süpürme aktivitesi, antiüreaz aktivite tayini ve demir indirgeme gücü gibi metodlarla tayin edildi. Antioksidanlar, reaktif oksijen çeşitlerinin meydana gelmesinin önlemek ve bunların oluşturmuş olduğu tahribatı engellemek için vücutta var olan bir tür savunma mekanizmalarıdır. Serbest radikalleri nötralize etmek amacıyla kullanılırlar. Antioksidan aktivitesinin kanıtı açıkça bizlere vücutta oluşabilecek hastalıklara karşı savunma mekanizmasının varlığını sergilemektedir. Elde edilen deneysel bulgulardan, benzimidazol bileşiklerinden özellikle 4 numaralı bileşiğin antioksidan aktivite değerlerinin diğer bileşiklere oranla daha yüksek olduğu saptandı. Tüm test bileşikleri, standart üreaz inhibitöründen (tiyoüre) daha yüksek aktivite gösterdi. En yüksek ve en düşük antiüreaz aktivite gösteren bileşikler sırasıyla 1 ve 5 numaralı bileşikler olarak belirlendi.

Keywords

ABTS aktivitesi, Antioksidan aktivite, Antiüreaz aktivite, Benzimidazol türevleri, Demir indirgeme gücü, DPPH aktivitesi

Supporting Institution

Giresun Üniversitesi BAP

Project Number

FEN-230123-03

Thanks

Makalenin tüm aşamalarında yapmış oldukları katkılardan dolayı editör kurulu ve hakemlere teşekkür ederiz.

Synthesis, Antioxidant and Antiurease Activities of Novel Benzimidazole Compounds

Abstract

In this study, a new series of benzimidazole derivatives (1-5) were synthesized and their antioxidant and antiurease activities were investigated by spectrophotometric methods. Antioxidant activities of synthesized new benzimidazole compounds, DPPH (1,1-diphenyl-2-picrylhydrazil) free radical scavenging activity, ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) radical scavenging activity were determined by methods such as antiurease activity assay and iron reducing power. Antioxidants are a kind of defense mechanism in the body to prevent the formation of reactive oxygen species and to prevent the damage they have caused. They are used to neutralize free radicals. Evidence of antioxidant activity clearly shows us that there is a defense mechanism against diseases that may occur in the body. From the experimental findings obtained, the antioxidant activity values of benzimidazole compounds, especially the number 4 compound, were found to be higher than the other compounds. All test compounds showed higher activity than the standard urease inhibitor (thiourea). Compounds with the highest and lowest antiurease activity were determined as compounds 1 and 5, respectively

Keywords

ABTS activity, Antioxidant activity, Antiurease activity, Benzimidazole derivatives, Iron reducing power, DPPH activity

Project Number

FEN-230123-03

References

• Amtul, Z., Rasheed, M., Chouhary, M. I., Supino, R., Khan, K. M., & Rahman, A. U. (2004). Kinetics of novel competitive inhibitors of urease enzymes by a focused library of oxadiazoles/thiadiazoles and triazoles. Biochem. Biophys. Res. Commun., 319(3), 1053-63. https://doi.org/10.1016/j.bbrc.2004.05.036
• Amtul, Z., Rahman, A. U., & Choudhary, M. I. (2002). Chemistry and mechanism of urease inhibition. Curr Med Chem., 9(14), 1323-48. https://doi.org/10.2174/0929867023369853
• Arnao, M. B., Cano, A. & Acosta, M. (2001). The hydrophilic and lipophilic contribution to total antioxidant activity. Food Chem., 73, 239–244. https://doi.org/10.1016/S0308-8146(00)00324-1
• Baltaş, N., Yılmaz F., & Menteşe E. (2016). Synthesis, Antioxidant, Xanthine Oxidase and Urease Inhibitory Activities of Some Chlorine Containing Benzimidazoles. Hacettepe J. Biol. & Chem., 44(3), 293–305
• Brand-Williams, W., Cuvelier, M. E., Berset, C., (1995). Use of a free radical method to evaluate antioxidant activity. Lebensm.-Wiss. Technol.-Food Sci. Technol., 28, 25–30. https://doi.org/10.1016/S0023-6438(95)80008-5
• Bilgin Sökmen, B., Serter, T., Çakır, D. & Bektaş, H. (2017). İlk Defa Sentezlenen Benzimidazol Türevlerinin Antioksidan Aktivitesinin İncelenmesi. Karadeniz Fen Bilimleri Dergisi, 7 (2), 87-95. https://doi.org/10.31466/kfbd.317706
• Castillo, I., Suwalsky, M., Gallardo, M. J., Troncoso, V., Sánchez-Eguía, B. N., Santiago-Osorio, E., Aguiñiga, I., & González-Ugarte, A. K. (2016). Structural and functional effects of benzimidazole/thioether–copper complexes with antitumor activity on cell membranes and molecular models. J. Inorg. Biochem., 156, 98–104. https://doi.org/10.1016/j.jinorgbio.2015.12.022
• Chandrasekera, N. S., Alling, T., Bailey, M. A., Files, M., Julie V. Early, J. V., Ollinger, J., Ovechkina, Y., Masquelin, T., Desai, P. V., Cramer, J. W., Hipskind, P. A., Odingo, J. O., & Parish, T. (2015). Identification of Phenoxyalkylbenzimidazoles with Antitubercular Activity. J Med Chem., 18, 7273–7285. https://doi.org/10.1021/acs.jmedchem.5b00546
• Chhabra, M., Sinha, S., Banerjee, S., & Paira P. (2016). An efficient green synthesis of 2-arylbenzothiazole analogues as potent antibacterial and anticancer agents. Bioorg. Med. Chem. Lett., 26, 213–217. https://doi.org/https://doi.org/10.1016/j.bmcl.2015.10.087
• Desai, K. G., & Desai, K. R. (2006). Green Route for the Heterocyclization of 2-Mercaptobenzimidazole into β-Lactum Segment Derivatives Containing –CONH– Bridge with Benzimidazole: Screening in Vitro Antimicrobial Activity with Various Microorganisms. Bioorganic & Medicinal Chemistry, 14, 8271-8279. https://doi.org/10.1016/j.bmc.2006.09.017
• Demirayak, Ş. (1985). Biyolojik Aktifliği Olan Bazı Benzimidazol Türevlerinin Sentezi, Fiziksel Sabitlerinin Saptanması ve Değerlendirilmesi [Doktora Tezi, Anadolu Üniversitesi Fen Bilimleri Enstitüsü].
• Eldebss, T. M. A., Farag, A. M., Abdulla, M. M., & Arafa, R., K. (2016). Novel benzo[d]imidazole-based heterocycles as broad spectrum anti-viral agents: Design, synthesis and exploration of molecular basis of action. Mini-Rev. Med. Chem., 16, 67–83. http://doi.org/10.2174/138955751601151029115533
• E. Mentes¸e, H. Bektas¸, S. Ülker, O. Bekircan, B. Kahveci, J Enzyme Inhib Med Chem 2014, 29, 64
• Fang, X., Jeyakkumar, P., Avula, S. R., Zhou, Q., & Zhou, C. (2016). Design, synthesis and biological evaluation of 5-fluorouracil-derived benzimidazoles as novel type of potential antimicrobial agents. Bioorg. Med. Chem. Lett., 26(11), 2584–2588. https://doi.org/10.1016/j.bmcl.2016.04.036
• Göker, H., Karaaslan, C., Puskullu, M. O., Yildiz, S., Duydu, Y., Üstündağ, A., & Yalcin, C. Ö. (2016). Synthesis and In Vitro Activity of Polyhalogenated 2-phenylbenzimidazoles as a New Class of anti-MRSA and Anti-VRE Agents. Chem. Biol. Drug. Des., 87, 57–68. https://doi.org/10.1111/cbdd.12623
• Güven M. (2000). Benzimidazol türevlerinin sentezi ve özelliklerinin incelenmesi [Yüksek lisans tezi]. İnönü Üniversitesi Fen Bilimleri Enstitüsü.
• Hoffmann, K. (1953). Imidazole and its derivatives. Intersciense Publishers, INC, New York.
• Kahveci, B., Menteşe, E., Özil, M., Ülker, S., & Ertürk, M. (2013). An efficient synthesis of benzimidazoles via a microwave technique and evaluation of their biological activities. Monatsh. Chem., 144, 993–1001. https://doi.org/10.1007/s00706-012-0916-0
• Kasnak, C., & Palamutoğlu, R. (2015). Doğal antioksidanların sınıflandırılması ve insan sağlığına etkileri. Türk Tarım – Gıda Bilim ve Teknoloji Dergisi, 3(5), 226-234. https://doi.org/10.24925/turjaf.v3i5.226-234.171
• Marinelli, M., Pellei, M., Cimarelli, C., Dias H.V.R., Marzano C., Tisato F., Porchia M., Gandin V., & Santini C. (2016). Novel multicharged silver(I)-NHC complexes derived from zwitterionic 1,3-symmetrically and 1,3-unsymmetrically substituted imidazoles and benzimidazoles: Synthesis and cytotoxic properties. J. Organomet. Chem., 806, 45–53. https://doi.org/10.1016/j.jorganchem.2016.01.018.
• Mobley, H. L. T., & Hausinger, R. P. (1989). Microbial ureases: significance, regulation, and molecular characterization. Microbiyol. Rev., 53(1), 85-108. https://doi.org/10.1128/mr.53.1.85-108.1989
• Mobley, H. L. T., Island, M. D., & Hausinger, R. P. (1995). Molecular biology of microbial ureases. Microbiyol. Rev., 59(3), 451-480. https://doi.org/10.1128/mr.59.3.451-480.1995
• Oyaizu, M. (1986). Studies on products of browning reactions: antioxidative activities of products of browning reaction prepared from glucosamine. Japanese Journal of Nutrition and Dietetics, 44(6), 307-315. http://dx.doi.org/10.5264/eiyogakuzashi.44.307
• Strelciunaite, V., Anusevicius, K., Tumosiene, I., Siugzdaite, J., Jonuskiene, I., Ramanauskaite, I., & Vytautas, M. (2016). synthesis of novel benzimidazoles 2-functionalized with pyrrolidinone and γ-amino acid with a high antibacterial activity. Heterocycles, 92, 235–251. https://doi.org/10.3987/COM-15-13343
• Stuchlíková, L., Jirásko, R., Skálová, L., Pavlík, F., Szotáková, B., Holčapek, M., Vaněk, T., & Podlipná, R. (2016). Metabolic pathways of benzimidazole anthelmintics in harebell (Campanula rotundifolia). Chemosphere, 157, 10-7. https://doi.org/10.1016/j.chemosphere.2016.05.015
• Van Slyke, D. D., & Archibald, R. M. (1944). Manometric, titrimetric and colorimetric methods for measurements of urease activity. The Journal of Biological Chemistry, 154, 623-642.