MTT-Based Assessment of the Anticancer Potential of a Known 1,2-Disubstituted Benzimidazole Compound on DLD-1 Cell Line
Year 2025,
Volume: 3 Issue: 2, 73 - 77, 25.11.2025
Yasemin Sunucu Karafakıoğlu
,
Elif Ece Akgün
,
İkbal Demet Nane
,
Senem Akkoç
Abstract
In this study, the cytotoxic effect of 1-(4-methylbenzyl)-2-p-tolyl-1H-benzo[d]imidazole (SL-13) was investigated on human colorectal cancer DLD-1 cells using the MTT assay. Treatment with SL-13 at various concentrations (100, 50, and 25 µM) for 72 hours resulted in a potent cytotoxic response with an IC₅₀ value of 6.093 µM, indicating strong antiproliferative activity. This potency surpasses that reported for many other benzimidazole derivatives tested against DLD-1 cells. These findings show that SL-13 is a promising candidate for further development in colorectal cancer therapy, warranting additional mechanistic and in vivo studies to elucidate its therapeutic potential.
Ethical Statement
As this research was conducted entirely on established cancer cell lines, ethics committee approval was not required.
Supporting Institution
Süleyman Demirel University
Project Number
TSG-2024-9516
Thanks
SA would like to thank the Suleyman Demirel University Research Fund for financial support with project number TSG-2024-9516.
References
-
Ahmad, N., Azad, M., Khan, A., & Azad, I. (2021). Benzimidazole as a promising antiviral heterocyclic Scaffold: A review. Journal of Science and Arts, 21(1), 273–284.
-
Akkoc, S., Kayser, V., İlhan, İ. Ö., Hibbs, D. E., Gök, Y., Williams, P. A., ... & 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.
-
Akkoc, S., Sahin, D., Muhammed, M. T., Yıldız, M., & Ilhan, I. O. (2023). Synthesis, characterization, antiproliferative activity, docking, and molecular dynamics simulation of new 1,3-dihydro-2H-benzimidazol-2-one derivatives. Journal of Biomolecular Structure and Dynamics, 42(21), 11495–11507.
-
Akkoç, S. (2021). Design, synthesis, characterization, and in vitro cytotoxic activity evaluation of 1, 2‐disubstituted benzimidazole compounds. Journal of Physical Organic Chemistry, 34(1), e4125.
-
Al-Douh, M. H., Sahib, H. B., Osman, H., Abd Hamid, S., & Salhimi, S. M. (2012). Anti-proliferation effects of benzimidazole derivatives on HCT-116 colon cancer and MCF-7 breast cancer cell lines. Asian Pacific journal of cancer prevention : APJCP, 13(8), 4075–4079.
-
Al-Nasser, S., Abdulla, M. H., Alhassan, N., Vaali-Mohammed, M. A., Al-Omar, S., Hamdi, N., Elnakady, Y., Matou-Nasri, S., & Mansour, L. (2024). A Benzimidazole-Based N-Heterocyclic Carbene Derivative Exhibits Potent Antiproliferative and Apoptotic Effects against Colorectal Cancer. Medicina (Kaunas, Lithuania), 60(9), 1379.
-
Ansari, K. F., & Lal, C. (2009). Synthesis and evaluation of some new benzimidazole derivatives as potential antimicrobial agents. European journal of medicinal chemistry, 44(5), 2294–2299.
-
Bayar, I., Turkmenoglu, B., & Akkoc, S. (2024). Biological and in Silico Studies on the Benzimidazole-Based Compounds. Chemistry Africa, 7(5), 2345-2352.
-
Bui, H. T. B., Htoo, Z. P., Hong, Q. V., Le, H. T., Tran, Q., Hnin, S. Y. Y., Do, K. M., & Morita, H. (2024). Facile Synthesis of 1,2-Disubstituted Benzimidazoles as Potent Cytotoxic Agents. Chemical & pharmaceutical bulletin, 72(11), 944–949.
-
Dienstmann, R., Rodon, J., Barretina, J., & Tabernero, J. (2013). Genomic medicine frontier in human solid tumors: prospects and challenges. Journal of Clinical Oncology, 31(15), 1874-1884.
-
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.
-
Haque, R. A., Ghdhayeb, M. Z., Budagumpi, S., Salman, A. W., Ahamed, M. B. K., & Majid, A. M. S. A. (2013). Non-symmetrically substituted N-heterocyclic carbene–Ag (I) complexes of benzimidazol-2-ylidenes: Synthesis, crystal structures, anticancer activity and transmetallation studies. Inorganica Chimica Acta, 394, 519-525.
-
He, L. J., Yang, D. L., Li, S. Q., Zhang, Y. J., Tang, Y., Lei, J., Frett, B., Lin, H. K., Li, H. Y., Chen, Z. Z., & Xu, Z. G. (2018). Facile construction of fused benzimidazole-isoquinolinones that induce cell-cycle arrest and apoptosis in colorectal cancer cells. Bioorganic & medicinal chemistry, 26(14), 3899–3908.
-
Kumar, R., Marianesan, A. B., & Pathak, S. (2024). Benzimidazole as a Privileged Scaffold in Drug Design and Discovery. Current topics in medicinal chemistry, 24(17), 1504–1528.
-
Moharana, A. K., Dash, R. N., Mahanandia, N. C., & Subudhi, B. B. (2022). Synthesis and anti-inflammatory activity evaluation of some benzimidazole derivatives. Pharmaceutical Chemistry Journal, 56(8), 1070–1074.
-
Shrivastava, N., Naim, M. J., Alam, M. J., Nawaz, F., Ahmed, S., & Alam, O. (2017). Benzimidazole Scaffold as anticancer agent: Synthetic approaches and structure–activity relationship. Archiv Der Pharmazie, 350(6), e201700040.
-
Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 71(3), 209-249.
-
Tumosienė, I., Peleckis, A., Jonuškienė, I., Vaickelionienė, R., Kantminienė, K., Šiugždaitė, J., ... & Mickevičius, V. (2018). Synthesis of novel 1, 2-and 2-substituted benzimidazoles with high antibacterial and antioxidant activity. Monatshefte für Chemie-Chemical Monthly, 149(3), 577-594.
-
Venugopal, S., Kaur, B., Verma, A., Wadhwa, P., Magan, M., Hudda, S., & Kakoty, V. (2023). Recent advances of benzimidazole as anticancer agents. Chemical biology & drug design, 102(2), 357–376.
-
Yavuz S. C. (2024). Synthesis of new two 1,2-disubstituted benzimidazole compounds: their in vitro anticancer and in silico molecular docking studies. BMC chemistry, 18(1), 146.
DLD-1 Hücre Hattında Bilinen 1,2-Disübstitüe Benzimidazol Bileşiğinin Antikanser Potansiyelinin MTT Bazlı Değerlendirilmesi
Year 2025,
Volume: 3 Issue: 2, 73 - 77, 25.11.2025
Yasemin Sunucu Karafakıoğlu
,
Elif Ece Akgün
,
İkbal Demet Nane
,
Senem Akkoç
Abstract
Bu çalışmada, 1-(4-metilbenzil)-2-p-tolil-1H-benzo[d]imidazolün (SL-13) sitotoksik etkisi, MTT testi kullanılarak insan kolorektal kanser DLD-1 hücreleri üzerinde araştırılmıştır. SL-13 ile çeşitli konsantrasyonlarda (100, 50 ve 25 µM) 72 saat boyunca uygulanan tedavi, 6,093 µM'lik bir IC₅₀ değeriyle güçlü bir sitotoksik yanıta yol açmış ve bu da güçlü antiproliferatif aktiviteye işaret etmiştir. Bu etki, DLD-1 hücrelerine karşı test edilen diğer birçok benzimidazol türevi için bildirilen etkiyi aşmaktadır. Bu bulgular, SL-13'ün kolorektal kanser tedavisinde daha fazla geliştirilmeye aday olduğunu göstermekte ve terapötik potansiyelini aydınlatmak için ek mekanistik ve in vivo çalışmalara ihtiyaç duyulmaktadır.
Ethical Statement
Bu araştırma tamamen yerleşik kanser hücre hatları üzerinde yürütüldüğünden etik kurul onayına gerek duyulmamıştır.
Supporting Institution
Süleyman Demirel Üniversitesi
Project Number
TSG-2024-9516
Thanks
SA, TSG-2024-9516 numaralı projeyle sağladığı finansal destekten dolayı Süleyman Demirel Üniversitesi Araştırma Fonu'na teşekkür etmek ister.
References
-
Ahmad, N., Azad, M., Khan, A., & Azad, I. (2021). Benzimidazole as a promising antiviral heterocyclic Scaffold: A review. Journal of Science and Arts, 21(1), 273–284.
-
Akkoc, S., Kayser, V., İlhan, İ. Ö., Hibbs, D. E., Gök, Y., Williams, P. A., ... & 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.
-
Akkoc, S., Sahin, D., Muhammed, M. T., Yıldız, M., & Ilhan, I. O. (2023). Synthesis, characterization, antiproliferative activity, docking, and molecular dynamics simulation of new 1,3-dihydro-2H-benzimidazol-2-one derivatives. Journal of Biomolecular Structure and Dynamics, 42(21), 11495–11507.
-
Akkoç, S. (2021). Design, synthesis, characterization, and in vitro cytotoxic activity evaluation of 1, 2‐disubstituted benzimidazole compounds. Journal of Physical Organic Chemistry, 34(1), e4125.
-
Al-Douh, M. H., Sahib, H. B., Osman, H., Abd Hamid, S., & Salhimi, S. M. (2012). Anti-proliferation effects of benzimidazole derivatives on HCT-116 colon cancer and MCF-7 breast cancer cell lines. Asian Pacific journal of cancer prevention : APJCP, 13(8), 4075–4079.
-
Al-Nasser, S., Abdulla, M. H., Alhassan, N., Vaali-Mohammed, M. A., Al-Omar, S., Hamdi, N., Elnakady, Y., Matou-Nasri, S., & Mansour, L. (2024). A Benzimidazole-Based N-Heterocyclic Carbene Derivative Exhibits Potent Antiproliferative and Apoptotic Effects against Colorectal Cancer. Medicina (Kaunas, Lithuania), 60(9), 1379.
-
Ansari, K. F., & Lal, C. (2009). Synthesis and evaluation of some new benzimidazole derivatives as potential antimicrobial agents. European journal of medicinal chemistry, 44(5), 2294–2299.
-
Bayar, I., Turkmenoglu, B., & Akkoc, S. (2024). Biological and in Silico Studies on the Benzimidazole-Based Compounds. Chemistry Africa, 7(5), 2345-2352.
-
Bui, H. T. B., Htoo, Z. P., Hong, Q. V., Le, H. T., Tran, Q., Hnin, S. Y. Y., Do, K. M., & Morita, H. (2024). Facile Synthesis of 1,2-Disubstituted Benzimidazoles as Potent Cytotoxic Agents. Chemical & pharmaceutical bulletin, 72(11), 944–949.
-
Dienstmann, R., Rodon, J., Barretina, J., & Tabernero, J. (2013). Genomic medicine frontier in human solid tumors: prospects and challenges. Journal of Clinical Oncology, 31(15), 1874-1884.
-
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.
-
Haque, R. A., Ghdhayeb, M. Z., Budagumpi, S., Salman, A. W., Ahamed, M. B. K., & Majid, A. M. S. A. (2013). Non-symmetrically substituted N-heterocyclic carbene–Ag (I) complexes of benzimidazol-2-ylidenes: Synthesis, crystal structures, anticancer activity and transmetallation studies. Inorganica Chimica Acta, 394, 519-525.
-
He, L. J., Yang, D. L., Li, S. Q., Zhang, Y. J., Tang, Y., Lei, J., Frett, B., Lin, H. K., Li, H. Y., Chen, Z. Z., & Xu, Z. G. (2018). Facile construction of fused benzimidazole-isoquinolinones that induce cell-cycle arrest and apoptosis in colorectal cancer cells. Bioorganic & medicinal chemistry, 26(14), 3899–3908.
-
Kumar, R., Marianesan, A. B., & Pathak, S. (2024). Benzimidazole as a Privileged Scaffold in Drug Design and Discovery. Current topics in medicinal chemistry, 24(17), 1504–1528.
-
Moharana, A. K., Dash, R. N., Mahanandia, N. C., & Subudhi, B. B. (2022). Synthesis and anti-inflammatory activity evaluation of some benzimidazole derivatives. Pharmaceutical Chemistry Journal, 56(8), 1070–1074.
-
Shrivastava, N., Naim, M. J., Alam, M. J., Nawaz, F., Ahmed, S., & Alam, O. (2017). Benzimidazole Scaffold as anticancer agent: Synthetic approaches and structure–activity relationship. Archiv Der Pharmazie, 350(6), e201700040.
-
Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 71(3), 209-249.
-
Tumosienė, I., Peleckis, A., Jonuškienė, I., Vaickelionienė, R., Kantminienė, K., Šiugždaitė, J., ... & Mickevičius, V. (2018). Synthesis of novel 1, 2-and 2-substituted benzimidazoles with high antibacterial and antioxidant activity. Monatshefte für Chemie-Chemical Monthly, 149(3), 577-594.
-
Venugopal, S., Kaur, B., Verma, A., Wadhwa, P., Magan, M., Hudda, S., & Kakoty, V. (2023). Recent advances of benzimidazole as anticancer agents. Chemical biology & drug design, 102(2), 357–376.
-
Yavuz S. C. (2024). Synthesis of new two 1,2-disubstituted benzimidazole compounds: their in vitro anticancer and in silico molecular docking studies. BMC chemistry, 18(1), 146.