Synthesis of Carbothioamide Substituted Benzimidazole Compounds and Investigation of Biological Activities

Yıl 2024, , 1 - 15, 30.04.2024

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

https://doi.org/10.46740/alku.1340210

Öz

Heterocyclic compounds containing nitrogen along with an oxygen atom in their structure are a major class of medicinal chemistry compounds due to their diverse biological applications. Benzimidazoles is also a heterocyclic aromatic organic compound in this group, carrying two different nitrogen (N) atoms in the ring structure. In this study, the antiurease and antioxidant activities of the synthesized benzimidazole derivatives (1-5) were investigated by spectrophotometric methods. Evidence of antioxidant activity clearly shows us that there is a defense mechanism against diseases that may occur in the body. All synthesized benzimidazole compounds showed antiurease and antioxidant activity. The most potent compound showing urease inhibition activity is number 2, and the least active compound is compound number 4. All compounds showed higher activity than thiourea. The compound with the highest antioxidant activity was determined as compound number 5, and the compound with the lowest antioxidant activity was determined as compound number 4.

Anahtar Kelimeler

ABTS and DPPH activity, Antiurease activity, Antioxidant activity, Benzimidazole

Proje Numarası

FEN-BAP-C-230123-03

Karbotiyoamidin Sübstitüye Benzimidazol Bileşiklerinin Sentezi ve Biyolojik Aktivitelerinin İncelenmesi

Öz

Yapılarında bir oksijen atomu ile birlikte nitrojen içeren heterosiklik bileşikler, çeşitli biyolojik uygulamaları nedeniyle önemli bir tıbbi kimya bileşikleri sınıfıdır. Benzimidazoller de bu grupta yer alıp, halka yapısında farklı yapıda iki azot (N) atomu taşıyan heterosiklik bir aromatik organik bileşiktir. Yapılan bu çalışmada, sentezlenen benzimidazol türevlerinin (1-5) antiüreaz ve antioksidan aktiviteleri spektrofotometrik metotlarla incelendi. Antioksidan aktivitesinin kanıtı bizlere vücutta oluşabilecek hastalıklara karşı savunma mekanizmasının var olduğunu açıkça göstermektedir. Sentezlenen tüm benzimidazol bileşikleri antiüreaz ve antioksidan aktivite gösterdi. Üreaz inhibisyon aktivitesi gösteren en güçlü bileşik 2 numaralı, en az aktif bileşik ise 4 numaralı bileşiktir. Tüm bileşikler tiyoüreden daha yüksek aktivite gösterdi. En yüksek antioksidan aktivitesine sahip bileşik 5 numaralı bileşik, en düşük antioksidan aktivitesine sahip bileşik ise 4 numaralı bileşikler olarak belirlendi.

Anahtar Kelimeler

ABTS ve DPPH aktivitesi, Antiüreaz aktivite, Antioksidan aktivite, Benzimidazol

Destekleyen Kurum

Giresun Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi

Proje Numarası

FEN-BAP-C-230123-03

Teşekkür

Yazarlar olarak bu çalışmayı FEN-BAP-C-230123-03 proje numarasıyla desteklemiş olan Giresun Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi’ne, makalenin inceleme ve değerlendirme aşamalarındaki tüm katkılardan dolayı editör ve hakemlere teşekkür ederiz.

Kaynakça

• [1] Arslaner, C. (2017). Benzimidazol Bileşiklerinin Sentezi ve Bazı Metal Komplekslerinin İncelenmesi, Yüksek Lisans Tezi, Selçuk Üniversitesi Fen Bilimleri Enstitüsü, Konya.
• [2] Habernickel, V. J. (1992). Alkyl-5-heterocyclic-benzimidazolyl-carbamate derivatives. Drugs Made in Germany, 35-97.
• [3] Walia, R., Hedaitullah, M., Naaz, S. F., Iqbal, K. and Lamba, H. S. (2011). Benzimidazole derivatives– an overview. IJRPC, 1(3), 565-574.
• [4] Demirayak, I., Kayagil, I. and Yurttas, L. (2011). Microwave supported synthesis of some novel 1,3- diarylpyrazino[1,2-a]benzimidazole derivatives and investigation of their anticancer activities. Eur J Med Chem, 46(1), 411-6. https://doi.org/10.1016/j.ejmech.2010.11.007
• [5] Tuncbilek, M., Kiper, T. and N. Altanlar, N. (2009). Synthesis and in vitro antimicrobial activity of some novel substituted benzimidazole derivatives having potent activity against MRSA. Eur J Med Chem, 44(3), 1024-33. https://doi.org/10.1016/j.ejmech.2008.06.026
• [6] Desai, G. D. and Desai, K. R. (2006) Green route for the heterocyclization of 2-mercaptobenzimidazole into beta-lactum segment derivatives containing -CONH- bridge with benzimidazole: Screening in vitro antimicrobial activity with various microorganisms. Bioorg Med Chem, 14(24), 8271-8279. https://doi.org/10.1016/j.bmc.2006.09.017
• [7] Mobinikhaledi, A., Foroughifar, N., Kalhor, M. and Mirabolfathy, M. (2009). Synthesis and antifungal activity of novel 2-benzimidazolylimino-5-arylidene-4-thiazolidinones. J Heterocycl Chem, 47, 77-80. https://doi.org/10.1002/jhet.264
• [8] Menteşe, E., Yılmaz, F., Baltaş, N., Bekircan, O., & Kahveci, B. (2015). Synthesis and antioxidant activities of some new triheterocyclic compounds containing benzimidazole, thiophene, and 1,2,4-triazole rings. J Enzyme Inhib Med Chem, 30(3), 435-41. https://doi.org/10.3109/14756366.2014.943203.
• [9] Kohler, P. (2001). The biochemical basis of anthelmintic action and resistance. Int J Parasitol, 31(4), 336-45. https://doi.org/10.1016/s0020-7519(01)00131-x.
• [10] Refaat, H. M. (2010). Synthesis and anticancer activity of some novel 2-substituted benzimidazole derivatives. Eur J Med Chem, 45(7), 2949-56. https://doi.org/10.1016/j.ejmech.2010.03.022
• [11] Menteşe, E., Yılmaz, F., Emirik, M., Ülker, S. and Kahveci, B. (2018). Synthesis, molecular docking and biological evaluation of some benzimidazole derivatives as potent pancreatic lipase inhibitors. Bioorg Chem, 76, 478-486. https://doi.org/ 10.1016/j.bioorg.2017.12.023
• [12] Yadagiri, B., Gurrala, S., Bantu, R., Nagarapu, L., Polepalli, S., Srujana, G. and Jain, N. (2015). Synthesis and evaluation of benzosuberone embedded with 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole moieties as new potential anti proliferative agents. Bioorg Med Chem Lett, 25(10), 2220-4. https://doi.org/10.1016/j.bmcl.2015.03.032.
• [13] Zoumpoulakis, P., Camoutsis, C., Pairas, G., Soković, M., Glamočlija, J., Potamitis, C., & Pitsas, A. (2012). Synthesis of novel sulfonamide-1,2,4-triazoles, 1,3,4-thiadiazoles and 1,3,4-oxadiazoles, as potential antibacterial and antifungal agents. Biological evaluation and conformational analysis studies. Bioorg Med Chem, 20(4), 1569-83. https://doi.org/10.1016/j.bmc.2011.12.031.
• [14] Menteşe, E., Ülker, S. and Kahveci, B. (2015). Synthesis and Study of alpha-Glucosidase Inhibitory, Antimicrobial and Antioxidant Activities of Some Benzimidazole Derivatives Containing Triazole, Thiadiazole, Oxadiazole, and Morpholine Rings. Chem Heterocycl Compd, 50(12), 1671-1682. https://doi.org/10.1007/s10593-015-1637-1.
• [15] Karaali, N. and Menteşe, E. (2016). Synthesis and study of antitumor activity of some new 2-(4- methoxybenzyl)-1H-benzimidazole derivatives bearing triazole, oxadiazole and ethanol moiety. Rev Roum Chim, 61(3), 187-192.
• [16] Menteşe, E., Bektas, H., Emirik, M., Bilgin Sökmen, B. and Kahveci, B. (2017). Synthesis and molecular docking study of some 5,6-dichloro-2-cyclopropyl-1H-benzimidazole derivatives bearing triazole, oxadiazole, and imine functionalities as potent inhibitors of urease. Bioorg Med Chem Lett, 27(13), 3014- 3018. https://doi.org/10.1016/j.bmcl.2017.05.019
• [17] Yılmaz, F., Menteşe, E. and Baltaş, N. (2017). Synthesis and antioxidant evaluation of some novel benzimidazole derivatives containing a triazole nucleus. Lett Drug Des Discovery, 14(2), 201-208. https://doi.org/ 10.2174/1570180813666160609082633.
• [18] El-Masry, A. H., Fahmy, H. H. and Abdelwahed, H. A. (2000). Synthesis and Antimicrobial Activity of Some New Benzimidazole Derivatives. Molecules, 5(12), 1429-1438. https://doi.org/10.3390/51201429
• [19] Barot, K. P., Manna, K. S., & Ghate, M. D. (2017). Design, synthesis and antimicrobial activities of some novel 1,3,4-thiadiazole, 1,2,4-triazole-5-thione and 1,3-thiazolan-4-one derivatives of benzimidazole. J Saudi Chem Soc, 21, 35-43. https://doi.org/10.1016/j.jscs.2013.09.010
• [20] Velik, J., Baliharova, V., Fink-Gremmels, J., Bull, S., Lamka, J. and Skalova, L. (2004). Benzimidazole drugs and modulation of biotransformation enzymes. Research in Veterinary Science, 76(2), 95-108. https://doi.org/10.1016/j.rvsc.2003.08.005
• [21] Zerner B. (1991). Recent advances in the chemistry of an old enzyme, urease. Bioorg Chem, 19, 116–131. https://doi.org/10.1016/0045-2068(91)90048-T
• [22] Sosa, V., Molin, T., Somoza, R., Paciucci, R., Kondoh, H. and Leonart, M. E. (2013). Oxidative stress and cancer: an overview. Ageing Res Rev, 12(1), 376-90. https://doi.org/ 10.1016/j.arr.2012.10.004.
• [23] Gumrukcuoglu, N. and Bilgin Sokmen, B. (2021). Synthesis and Antioxidant Activities of New 2-(4- methylphenylsulphonyl)-5-Aryl1,3,4-Oxadiazole Compounds. Erzincan University Fen Bilimleri Enstitüsü Dergisi Journal of Science and Technology, 14(1), 232-240. https://doi.org/10.18185/erzifbed.823431.
• [24] Blois, M. S. (1958). Antioxidant determinations by the use of a stable free radical. Nature, 181, 1119-1200. https://doi.org/10.1038/1811199a0
• [25] Foye, W.O. (1995). Cancer Chemotherapeutic Agents. American Chemical Society. 1-212.
• [26] Mentese, E., Bektas, H., Ulker, S., Bekircan, O. and Kahveci, B. (2014). Microwave-assisted synthesis of new benzimidazole derivatives with lipase inhibition activity. Journal of Enzyme Inhibition and Medicinal Chemistry, 29 (1):64-68. https://doi.org/10.3109/14756366.2012.753880.
• [27] Akgün, H., Gümrükçüoğlu, T. İ., Bektaş, H. and Bilgin Sökmen, B. (2023). Yeni Benzimidazol Bileşiklerinin Sentezi, Antioksidan ve Antiüreaz Aktiviteleri. Doğu Karadeniz Sağlık Bilimleri Dergisi, 2(2), 60-76. https://doi.org/10.59312/ebshealth.1326437
• [28] Van Slyke, D. D. V. and Archibald, R. M. (1944). Manometric, titrimetric, and colorimetric methods for measurement of urease activity. Journal of Biological Chemistry, 154(3), 623-642. https://doi.org/10.1016/S0021-9258(18)71897-8
• [29] Brand-Williams, W., Cuvelier, M. E. and 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
• [31] Koleva, I. I., van Beek T. A., Linssen, J. P. H., de Groot, A. and Evstatieva L. N. (2002). Screening of plant extracts for antioxidant activity: a comparative study on three testing methods. Phytochem. Anal. 13(1), 8- 17. https://10.1002/pca.611.
• [31] Arnao, M. B., Cano, A. and 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.
• [32] 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. https://doi.org/10.5264/eiyogakuzashi.44.307
• [33] 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