Araştırma Makalesi
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Antiproliferative effect of silver compounds containing benzimidazole ring

Yıl 2025, , 1 - 8, 15.04.2025

Dilek Bahar , Senem Akkoç , Buket Banu Özkan

https://doi.org/10.23902/trkjnat.1549105

Öz

With its significant biological activities, the benzimidazole nucleus is a crucial pharmacophore in medicine. Recent studies have focused on the synthesis and biological activity of benzimidazole compounds. Therefore, this study prepared a series of N-heterocyclic silver compounds containing benzimidazole nuclei. These complexes were cultured with lung (A549), colon (CaCo2), breast (MCF7), prostate (PC3) cancer cell lines, and healthy lung (WI38) cell line, and their anticancer effects were investigated through MTT, apoptosis determination, and oxidative stress tests. The results revealed that the presence of drug candidates was more practical than that of commercially used cisplatin.

Anahtar Kelimeler

Apoptosis cytotoxic activity Ag-NHC oxidative stress.

Etik Beyan

Since the article does not contain any studies with human or animal subject, its approval to the ethics committee was not required.

Destekleyen Kurum

Erciyes University Research Fund

Proje Numarası

TKB-2020-10346

Teşekkür

We would like to thank GENKOK, Erciyes University Research Fund (Eru BAP) and the Proofreading & Editing Office of the Dean for Research of Erciyes University for copyediting and proofreading service for an earlier version of the manuscript.

Kaynakça

  • 1. Abdelgawad, M.A., Bakr, R.B., Ahmad, W., Al-Sanea, M.M. & Elshemy, H.A.H. 2019. New pyrimidine-benzoxazole/benzimidazole hybrids: Synthesis, antioxidant, cytotoxic activity, in vitro cyclooxygenase and phospholipase A2-V inhibition. Bioorganic Chemistry, 92: 1-6. https://doi.org/10.1016/j.bioorg.2019.103218
  • 2. Akkoç, S. 2019. Derivatives of 1‐(2‐(Piperidin‐1‐yl) ethyl)‐1H‐benzo [d] imidazole: Synthesis, characterization, determining of electronic properties and cytotoxicity studies. ChemistrySelect, 4(17): 4938-4943. https://doi.org/10.1002/slct.201900353
  • 3. Akkoç, S., Gök, Y., İlhan, İ.Ö. & Kayser, V. 2016a. N-Methylphthalimide-substituted benzimidazolium salts and PEPPSI Pd–NHC complexes: synthesis, characterization and catalytic activity in carbon–carbon bond-forming reactions. Beilstein Journal of Organic Chemistry, 12(1): 81-88. https://doi.org/10.3762/bjoc.12.9
  • 4. Akkoç, S., Gök, Y., Özdemir, İ. & Günal, S. 2014. N-Heterocyclic Carbene Silver Complexes: Synthesis, Characterization and in Vitro Antimicrobial Studies. Journal of the Chinese Advanced Materials Society, 2(1): 20-30. https://doi.org/10.1080/22243682.2014.882795
  • 5. Akkoç, S., Kayser, V. & İlhan, İ.Ö. 2019. Synthesis and in vitro anticancer evaluation of some benzimidazolium salts. Journal of Heterocyclic Chemistry, 56(10): 2934-2944. https://doi.org/10.1002/jhet.3687
  • 6. Akkoç, S., Kayser, V., İlhan, İ.Ö., Hibbs, D.E., Gök, Y., Williams, P.A., Hawkins, B. & Lai, F. 2017. New compounds based on a benzimidazole nucleus: synthesis, characterization and cytotoxic activity against breast and colon cancer cell lines. Journal of Organometallic Chemistry, 839: 98-107. https://doi.org/10.1016/j.jorganchem.2017.03.037
  • 7. Akkoç, S., Özer İlhan, İ., Gök, Y., Upadhyay, P.J. & Kayser, V. 2016b. In vitro cytotoxic activities of new silver and PEPPSI palladium N-heterocyclic carbene complexes derived from benzimidazolium salts. Inorganica Chimica Acta, 449: 75-81. https://doi.org/10.1016/j.ica.2016.05.001
  • 8. Aslan, H. G., Akkoç, S. & Kökbudak, Z. 2020. Anticancer activities of various new metal complexes prepared from a Schiff base on A549 cell line. Inorganic Chemistry Communications, 111: 11-6. https://doi.org/10.1016/j.inoche.2019.107645
  • 9. Bansal, Y. & Silakari, O. 2012. The therapeutic journey of benzimidazoles: A review. Bioorganic Medicinal Chemistry, 20(21): 6208-6236. https://doi.org/10.1016/j.bmc.2012.09.013
  • 10. Block, K.I., Gyllenhaal, C., Lowe, L., Amedei, A., Amin, A.R., Amin, A., Ashraf, S.S. 2015. A broad-spectrum integrative design for cancer prevention and therapy. In Seminars in Cancer Biology, 35(Suppl): 276-304. https://doi:10.1016/j.semcancer.2015.09.007
  • 11. Chaicharoenaudomrung, N., Kunhorm, P. & Noisa, P. 2019. Three-dimensional cell culture systems as an in vitro platform for cancer and stem cell modeling. World Journal of Stem Cells, 11(12): 1065-1083. https://doi:10.4252/wjsc.v11.i12.1065
  • 12. Gök, Y., Akkoç, S., Albayrak, S., Akkurt, M. & Tahir, M.N. 2014. N‐Phenyl‐substituted carbene precursors and their silver complexes: synthesis, characterization and antimicrobial activities. Applied Organometallic Chemistry, 28(4): 244-251. https://doi.org/10.1002/aoc.3116
  • 13. Gök, Y., Akkoc, S., Çelikal, Ö.Ö., Özdemir, İ. & Günal, S. 2019. In vitro antimicrobial studies of naphthalen-1-ylmethyl substituted silver N-heterocyclic carbene complexes. Arabian Journal of Chemistry, 12(8): 2513-2518. https://doi.org/10.1016/j.arabjc.2015.04.019
  • 14. Siegel, R., Giaquinto A.N. & Jemal A. 2024. Cancer statistics. CA: A Cancer Journal For Clinicians, 60(5): 277-300. https://doi.org/10.3322/caac.21820
  • 15. Liu, T., Sun, C., Xing, X., Jing, L., Tan, R., Luo, Y. & Zhao, Y. 2012. Synthesis and evaluation of 2-[2-(phenylthiomethyl)-1H-benzo [d] imidazol-1-yl) acetohydrazide derivatives as antitumor agents. Bioorganic & Medicinal Chemistry Letters, 22(9): 3122-3125. https://doi.org/10.1016/j.bmcl.2012.03.061
  • 16. Mavrova, A.T., Wesselinova, D., Vassilev, N. & Tsenov, J.A. 2013. Design, synthesis and antiproliferative properties of some new 5-substituted-2-iminobenzimidazole derivatives. European Journal of Medicinal Chemistry, 63: 696-701. https://doi.org/10.1016/j.ejmech.2013.03.010
  • 17. Özil, M., Parlak, C. & Baltaş, N. 2018. A simple and efficient synthesis of benzimidazoles containing piperazine or morpholine skeleton at C-6 position as glucosidase inhibitors with antioxidant activity. Bioorganic Chemistry, 76: 468-477. https://doi.org/10.1016/j.bioorg.2017.12.019
  • 18. Shingalapur, R.V., Hosamani, K.M., Keri, R.S. & Hugar, M.H. 2010. Derivatives of benzimidazole pharmacophore: Synthesis, anticonvulsant, antidiabetic and DNA cleavage studies. European Journal of Medicinal Chemistry, 45(5): 1753-1759. https://doi.org/10.1016/j.ejmech.2010.01.007
  • 19. Taha, M., Mosaddik, A., Rahim, F., Ali, S., Ibrahim, M. & Almandil, N.B., 2018. Synthesis, antiglycation and antioxidant potentials of benzimidazole derivatives. Journal of King Saud University -Science, 32(1): 191-194. https://doi.org/10.1016/j.jksus.2018.04.003
  • 20. Thimmegowda, N.R., Swamy, S.N., Kumar, C.A., Kumar, Y.S., Chandrappa, S., Yip, G. W. & Rangappa, K.S. 2008. Synthesis, characterization and evaluation of benzimidazole derivative and its precursors as inhibitors of MDA-MB-231 human breast cancer cell proliferation. Bioorganic & Medicinal Chemistry Letters. 18(1): 432-435. https://doi.org/10.1016/j.bmcl.2007.08.078
  • 21. Tonelli, M., Novelli, F., Tasso, B., Vazzana, I., Sparatore, A., Boido, V., Sparatore, F., La Colla, P., Sanna, G., Giliberti, G., Busonera, B., Farci, P., Ibba, C. & Loddo, R. 2014. Antiviral activity of benzimidazole derivatives. III. Novel anti-CVB-5, anti-RSV and anti-Sb-1 agents. Bioorganic Medicinal Chemistry, 22(17): 4893-4909. https://doi.org/10.1016/j.bmc.2014.06.043

Yıl 2025, , 1 - 8, 15.04.2025

Dilek Bahar , Senem Akkoç , Buket Banu Özkan

https://doi.org/10.23902/trkjnat.1549105

Öz

Benzimidazol çekirdeği önemli biyolojik aktiviteleri ile tıpta önemli bir farmakofordur. Son çalışmalar benzimidazol bileşiklerinin sentezi ve biyolojik aktivitesine odaklanmıştır. Bu nedenle, bu çalışmada benzimidazol çekirdekleri içeren bir dizi N-heterosiklik gümüş bileşiği hazırlamıştır. Bileşiklerin etkilerini incelemek için in vitro hücre kültür deneyleri yapılmıştır. Bileşikler akciğer (A549), kolon (CaCo2), meme (MCF7), prostat (PC3) kanser hücre hatları ve sağlıklı akciğer (WI38) hücre hattı ile kültüre edilmiş ve bileşiklerin antikanser etkileri bu hücreler üzerinde MTT hücre çoğalma testi, apoptoz tayini ve oksidatif stres testleri yapılarak araştırılmıştır. Sonuçlar ilaç adaylarının varlığının ticari olarak kullanılan sisplatinden daha pratik olduğunu ortaya koymuştur.

Proje Numarası

TKB-2020-10346

Kaynakça

  • 1. Abdelgawad, M.A., Bakr, R.B., Ahmad, W., Al-Sanea, M.M. & Elshemy, H.A.H. 2019. New pyrimidine-benzoxazole/benzimidazole hybrids: Synthesis, antioxidant, cytotoxic activity, in vitro cyclooxygenase and phospholipase A2-V inhibition. Bioorganic Chemistry, 92: 1-6. https://doi.org/10.1016/j.bioorg.2019.103218
  • 2. Akkoç, S. 2019. Derivatives of 1‐(2‐(Piperidin‐1‐yl) ethyl)‐1H‐benzo [d] imidazole: Synthesis, characterization, determining of electronic properties and cytotoxicity studies. ChemistrySelect, 4(17): 4938-4943. https://doi.org/10.1002/slct.201900353
  • 3. Akkoç, S., Gök, Y., İlhan, İ.Ö. & Kayser, V. 2016a. N-Methylphthalimide-substituted benzimidazolium salts and PEPPSI Pd–NHC complexes: synthesis, characterization and catalytic activity in carbon–carbon bond-forming reactions. Beilstein Journal of Organic Chemistry, 12(1): 81-88. https://doi.org/10.3762/bjoc.12.9
  • 4. Akkoç, S., Gök, Y., Özdemir, İ. & Günal, S. 2014. N-Heterocyclic Carbene Silver Complexes: Synthesis, Characterization and in Vitro Antimicrobial Studies. Journal of the Chinese Advanced Materials Society, 2(1): 20-30. https://doi.org/10.1080/22243682.2014.882795
  • 5. Akkoç, S., Kayser, V. & İlhan, İ.Ö. 2019. Synthesis and in vitro anticancer evaluation of some benzimidazolium salts. Journal of Heterocyclic Chemistry, 56(10): 2934-2944. https://doi.org/10.1002/jhet.3687
  • 6. Akkoç, S., Kayser, V., İlhan, İ.Ö., Hibbs, D.E., Gök, Y., Williams, P.A., Hawkins, B. & Lai, F. 2017. New compounds based on a benzimidazole nucleus: synthesis, characterization and cytotoxic activity against breast and colon cancer cell lines. Journal of Organometallic Chemistry, 839: 98-107. https://doi.org/10.1016/j.jorganchem.2017.03.037
  • 7. Akkoç, S., Özer İlhan, İ., Gök, Y., Upadhyay, P.J. & Kayser, V. 2016b. In vitro cytotoxic activities of new silver and PEPPSI palladium N-heterocyclic carbene complexes derived from benzimidazolium salts. Inorganica Chimica Acta, 449: 75-81. https://doi.org/10.1016/j.ica.2016.05.001
  • 8. Aslan, H. G., Akkoç, S. & Kökbudak, Z. 2020. Anticancer activities of various new metal complexes prepared from a Schiff base on A549 cell line. Inorganic Chemistry Communications, 111: 11-6. https://doi.org/10.1016/j.inoche.2019.107645
  • 9. Bansal, Y. & Silakari, O. 2012. The therapeutic journey of benzimidazoles: A review. Bioorganic Medicinal Chemistry, 20(21): 6208-6236. https://doi.org/10.1016/j.bmc.2012.09.013
  • 10. Block, K.I., Gyllenhaal, C., Lowe, L., Amedei, A., Amin, A.R., Amin, A., Ashraf, S.S. 2015. A broad-spectrum integrative design for cancer prevention and therapy. In Seminars in Cancer Biology, 35(Suppl): 276-304. https://doi:10.1016/j.semcancer.2015.09.007
  • 11. Chaicharoenaudomrung, N., Kunhorm, P. & Noisa, P. 2019. Three-dimensional cell culture systems as an in vitro platform for cancer and stem cell modeling. World Journal of Stem Cells, 11(12): 1065-1083. https://doi:10.4252/wjsc.v11.i12.1065
  • 12. Gök, Y., Akkoç, S., Albayrak, S., Akkurt, M. & Tahir, M.N. 2014. N‐Phenyl‐substituted carbene precursors and their silver complexes: synthesis, characterization and antimicrobial activities. Applied Organometallic Chemistry, 28(4): 244-251. https://doi.org/10.1002/aoc.3116
  • 13. Gök, Y., Akkoc, S., Çelikal, Ö.Ö., Özdemir, İ. & Günal, S. 2019. In vitro antimicrobial studies of naphthalen-1-ylmethyl substituted silver N-heterocyclic carbene complexes. Arabian Journal of Chemistry, 12(8): 2513-2518. https://doi.org/10.1016/j.arabjc.2015.04.019
  • 14. Siegel, R., Giaquinto A.N. & Jemal A. 2024. Cancer statistics. CA: A Cancer Journal For Clinicians, 60(5): 277-300. https://doi.org/10.3322/caac.21820
  • 15. Liu, T., Sun, C., Xing, X., Jing, L., Tan, R., Luo, Y. & Zhao, Y. 2012. Synthesis and evaluation of 2-[2-(phenylthiomethyl)-1H-benzo [d] imidazol-1-yl) acetohydrazide derivatives as antitumor agents. Bioorganic & Medicinal Chemistry Letters, 22(9): 3122-3125. https://doi.org/10.1016/j.bmcl.2012.03.061
  • 16. Mavrova, A.T., Wesselinova, D., Vassilev, N. & Tsenov, J.A. 2013. Design, synthesis and antiproliferative properties of some new 5-substituted-2-iminobenzimidazole derivatives. European Journal of Medicinal Chemistry, 63: 696-701. https://doi.org/10.1016/j.ejmech.2013.03.010
  • 17. Özil, M., Parlak, C. & Baltaş, N. 2018. A simple and efficient synthesis of benzimidazoles containing piperazine or morpholine skeleton at C-6 position as glucosidase inhibitors with antioxidant activity. Bioorganic Chemistry, 76: 468-477. https://doi.org/10.1016/j.bioorg.2017.12.019
  • 18. Shingalapur, R.V., Hosamani, K.M., Keri, R.S. & Hugar, M.H. 2010. Derivatives of benzimidazole pharmacophore: Synthesis, anticonvulsant, antidiabetic and DNA cleavage studies. European Journal of Medicinal Chemistry, 45(5): 1753-1759. https://doi.org/10.1016/j.ejmech.2010.01.007
  • 19. Taha, M., Mosaddik, A., Rahim, F., Ali, S., Ibrahim, M. & Almandil, N.B., 2018. Synthesis, antiglycation and antioxidant potentials of benzimidazole derivatives. Journal of King Saud University -Science, 32(1): 191-194. https://doi.org/10.1016/j.jksus.2018.04.003
  • 20. Thimmegowda, N.R., Swamy, S.N., Kumar, C.A., Kumar, Y.S., Chandrappa, S., Yip, G. W. & Rangappa, K.S. 2008. Synthesis, characterization and evaluation of benzimidazole derivative and its precursors as inhibitors of MDA-MB-231 human breast cancer cell proliferation. Bioorganic & Medicinal Chemistry Letters. 18(1): 432-435. https://doi.org/10.1016/j.bmcl.2007.08.078
  • 21. Tonelli, M., Novelli, F., Tasso, B., Vazzana, I., Sparatore, A., Boido, V., Sparatore, F., La Colla, P., Sanna, G., Giliberti, G., Busonera, B., Farci, P., Ibba, C. & Loddo, R. 2014. Antiviral activity of benzimidazole derivatives. III. Novel anti-CVB-5, anti-RSV and anti-Sb-1 agents. Bioorganic Medicinal Chemistry, 22(17): 4893-4909. https://doi.org/10.1016/j.bmc.2014.06.043
Toplam 21 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Hücre Gelişimi, Proliferasyon ve Ölümü
Bölüm Araştırma Makalesi/Research Article
Yazarlar

Dilek Bahar 0000-0002-4916-5071

Senem Akkoç 0000-0002-1260-9425

Buket Banu Özkan 0000-0002-1589-9464

Proje Numarası TKB-2020-10346
Erken Görünüm Tarihi 20 Aralık 2024
Yayımlanma Tarihi 15 Nisan 2025
Gönderilme Tarihi 13 Eylül 2024
Kabul Tarihi 2 Kasım 2024
Yayımlandığı Sayı Yıl 2025

Kaynak Göster

APA Bahar, D., Akkoç, S., & Özkan, B. B. (2025). Antiproliferative effect of silver compounds containing benzimidazole ring. Trakya University Journal of Natural Sciences, 26(1), 1-8. https://doi.org/10.23902/trkjnat.1549105
AMA Bahar D, Akkoç S, Özkan BB. Antiproliferative effect of silver compounds containing benzimidazole ring. Trakya Univ J Nat Sci. Nisan 2025;26(1):1-8. doi:10.23902/trkjnat.1549105
Chicago Bahar, Dilek, Senem Akkoç, ve Buket Banu Özkan. “Antiproliferative Effect of Silver Compounds Containing Benzimidazole Ring”. Trakya University Journal of Natural Sciences 26, sy. 1 (Nisan 2025): 1-8. https://doi.org/10.23902/trkjnat.1549105.
EndNote Bahar D, Akkoç S, Özkan BB (01 Nisan 2025) Antiproliferative effect of silver compounds containing benzimidazole ring. Trakya University Journal of Natural Sciences 26 1 1–8.
IEEE D. Bahar, S. Akkoç, ve B. B. Özkan, “Antiproliferative effect of silver compounds containing benzimidazole ring”, Trakya Univ J Nat Sci, c. 26, sy. 1, ss. 1–8, 2025, doi: 10.23902/trkjnat.1549105.
ISNAD Bahar, Dilek vd. “Antiproliferative Effect of Silver Compounds Containing Benzimidazole Ring”. Trakya University Journal of Natural Sciences 26/1 (Nisan 2025), 1-8. https://doi.org/10.23902/trkjnat.1549105.
JAMA Bahar D, Akkoç S, Özkan BB. Antiproliferative effect of silver compounds containing benzimidazole ring. Trakya Univ J Nat Sci. 2025;26:1–8.
MLA Bahar, Dilek vd. “Antiproliferative Effect of Silver Compounds Containing Benzimidazole Ring”. Trakya University Journal of Natural Sciences, c. 26, sy. 1, 2025, ss. 1-8, doi:10.23902/trkjnat.1549105.
Vancouver Bahar D, Akkoç S, Özkan BB. Antiproliferative effect of silver compounds containing benzimidazole ring. Trakya Univ J Nat Sci. 2025;26(1):1-8.

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