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Heterosiklik Benzimidazol–Tiyoeter Türevlerinin İnsan Deri Fibroblast Hücrelerinin Çoğalması Üzerindeki Etkisi

Year 2025, Volume: 18 Issue: 2, 464 - 475, 31.08.2025
https://doi.org/10.18185/erzifbed.1726734

Abstract

Benzimidazolün, farmakolojik ve fizikokimyasal özelliklerinden dolayı antikanser çalışmalarında önemli bir yer tutmasına rağmen normal hücre hatlarıda sitotoksik ve güvenlik profillerine ilişkin veriler sınırlı kalmaktadır. Bu sebeple bu çalışmada heterosiklik benzimidazol-tiyoeter bileşiklerinin İnsan deri Fibroblast (HDFa) hücre hattının poliferasyonuna etkisi 10 nM, 100 nM, 500 nM, 1 µM konsantasyonlarda ve 24 ile 48 saat süre ile incelenmiştir. Heterosiklik benzimidazol-tiyoeter moleküllerinden 11 ve 12 için IC50 değerleri 24 ve 48 saat için sırasıyla; 117.93, 13.2 nM ile 52.14, 28.2 nM olarak bulunmuştur. Çalışmada heterosiklik benzimidazol-tiyoeter bileşik-11 için kontrol grubuna en yakın canlılık gösteren konsantrasyonlarda 24 ve 48 saatte 10 nM olarak bulunmuştur. Ayrıca bileşik-11 için 24. saatte 500 nM ve 1 µM konstrasyonları istatiksel olarak anlamlı bulunurken; bileşik-12 için ise 24 saatte 100 nM 500 nM ve 1 µM konstrasyonları istatiksel olarak anlamlı bulunurken 48. Saatte bütün konsantrasyonlar istatiksel olarak anlamlı bulunmuştur (p<0.05).

Project Number

-

References

  • [1] Wright, J.B., (1951) The Chemistry of the Benzimidazoles, Chem Rev, 48 397–541.
  • [2] Bansal, Y., Kaur, M., Bansal, G., (2019) Antimicrobial Potential of Benzimidazole Derived Molecules, Mini-Reviews in Medicinal Chemistry, 19 624–646.
  • [3] Mendogralo, E.Y., Nesterova, L.Y., Nasibullina, E.R., Shcherbakov, R.O., Myasnikov, D.A., Tkachenko, A.G., Sidorov, R.Y., Uchuskin, M.G., (2023) Synthesis, Antimicrobial and Antibiofilm Activities, and Molecular Docking Investigations of 2-(1H-Indol-3-Yl)-1H- Benzo[d]Imidazole Derivatives, Molecules, 28 7095.
  • [4] Coelho, R.A., Figueiredo-Carvalho, M.H.G., Almeida-Silva, F., de Souza Rabello, V.B., de Souza, G.R., Sangenito, L.S., Joffe, L.S., Santos, A.L.S., da Silva Lourenço, M.C., Rodrigues, M.L., Almeida-Paes, R., (2023) Repurposing Benzimidazoles against Causative Agents of Chromoblastomycosis: Albendazole Has Superior In Vitro Activity Than Mebendazole and Thiabendazole, Journal of Fungi, 9 753.
  • [5] Sharma, A., Luxami, V., Paul, K., (2015) Purine-Benzimidazole Hybrids: Synthesis, Single Crystal Determination and in Vitro Evaluation of Antitumor Activities, Eur J Med Chem, 93 414–422.
  • [6] Sun, D., Wang, C., Fan, Y., Gu, J., (2023) Identification, Structure Elucidation and Origin of a Common Pyridinium-Thiocyanate Intermediate in Electrospray Mass Spectrometry among the Benziamidazole-Class Proton Pump Inhibitors, J Pharm Anal, 13 683–688.
  • [7] Choudhary, A., Viradiya, R.H., Ghoghari, R.N., Chikhalia, K.H., (2023) Recent Scenario for the Synthesis of Benzimidazole Moiety(2020–2022), ChemistrySelect, 8.
  • [8] Yadav, G., Ganguly, S., (2015) Structure Activity Relationship (SAR) Study of Benzimidazole Scaffold for Different Biological Activities: A Mini-Review, Eur J Med Chem, 97 419–443.
  • [9] Haider, K., Shahar Yar, M., (2022) Advances of Benzimidazole Derivatives as Anticancer Agents: Bench to Bedside. In S. Basak (Ed.), Benzimidazole derivatives (pp. 1–24). IntechOpen, United Kingdom.
  • [10] Aroua, L.M., (2020) Novel Mixed Complexes Derived from Benzoimidazolphenylethanamine and 4-(Benzoimidazol-2-Yl)Aniline: Synthesis, Characterization, Antibacterial Evaluation and Theoretical Prediction of Toxicity, Asian Journal of Chemistry, 32 1266–1272.
  • [11] Tayade, A.P., Pawar, R.P., (2022) The Microwave Assisted and Efficient Synthesis of 2- Substituted Benzimidazole Mono-Condensation of O-Phenylenediamines and Aldehyde, Polycycl Aromat Compd, 42(1), 1474–1478.
  • [12] Dokla, E.M.E., Abutaleb, N.S., Milik, S.N., Li, D., El-Baz, K., Shalaby, M.-A.W., Al- Karaki, R., Nasr, M., Klein, C.D., Abouzid, K.A.M., Seleem, M.N., (2020) Development of Benzimidazole-Based Derivatives as Antimicrobial Agents and Their Synergistic Effect with Colistin against Gram-Negative Bacteria, Eur J Med Chem, 186, 111850.
  • [13] Maghraby, M.T.-E., Abou-Ghadir, O.M.F., Abdel-Moty, S.G., Ali, A.Y., Salem, O.I.A., (2020) Novel Class of Benzimidazole-Thiazole Hybrids: The Privileged Scaffolds of Potent Anti-Inflammatory Activity with Dual Inhibition of Cyclooxygenase and 15-Lipoxygenase Enzymes, Bioorg Med Chem, 28(1), 115403.
  • [14] Imran, M., Al Kury, L.T., Nadeem, H., Shah, F.A., Abbas, M., Naz, S., Khan, A., Li, S., (2020) Benzimidazole Containing Acetamide Derivatives Attenuate Neuroinflammation and Oxidative Stress in Ethanol-Induced Neurodegeneration, Biomolecules, 10(1), 108.
  • [15] Doganc, F., Celik, I., Eren, G., Kaiser, M., Brun, R., Goker, H., (2021) Synthesis, in Vitro Antiprotozoal Activity, Molecular Docking and Molecular Dynamics Studies of Some New Monocationic Guanidinobenzimidazoles, Eur J Med Chem, 221, 113545.
  • [16] Choudhary, S., Arora, M., Verma, H., Kumar, M., Silakari, O., (2021) Benzimidazole Based Hybrids against Complex Diseases: A Catalogue of the SAR Profile, Eur J Pharmacol, 899, 174027.
  • [17] Miller, J.F., Turner, E.M., Gudmundsson, K.S., Jenkinson, S., Spaltenstein, A., Thomson, M., Wheelan, P., (2010) Novel N-Substituted Benzimidazole CXCR4 Antagonists as Potential Anti-HIV Agents, Bioorg Med Chem Lett, 20(7), 2125–2128.
  • [18] Pan, T., He, X., Chen, B., Chen, H., Geng, G., Luo, H., Zhang, H., Bai, C., (2015) Development of Benzimidazole Derivatives to Inhibit HIV-1 Replication through Protecting APOBEC3G Protein, Eur J Med Chem, 95, 500–513. [19] Singh, I., Luxami, V., Paul, K., (2019) Synthesis and in Vitro Evaluation of Naphthalimide–Benzimidazole Conjugates as Potential Antitumor Agents, Org Biomol Chem, 17(22), 5349–5366.
  • [20] Wang, Z., Deng, X., Xiong, R., Xiong, S., Liu, J., Cao, X., Lei, X., Chen, Y., Zheng, X., Tang, G., (2018) Design, Synthesis and Biological Evaluation of 3′,4′,5′-Trimethoxy Flavonoid Benzimidazole Derivatives as Potential Anti-Tumor Agents, Medchemcomm, 9(2), 305–315.
  • [21] Hranjec, M., Starčević, K., Pavelić, S.K., Lučin, P., Pavelić, K., Karminski Zamola, G., (2011) Synthesis, Spectroscopic Characterization and Antiproliferative Evaluation in Vitro of Novel Schiff Bases Related to Benzimidazoles, Eur J Med Chem, 46, 2274–2279.
  • [22] Radzikowska-Bűchner, E., Radej, S., Niezabitowska, E., Sitarz, R., Szewc, M., (2025) Potential of Using New Indole- and Benzimidazo[1,2-C]Quinazolines in Anticancer Therapy Based on Mesenchymal Stem Cells, Cancer Manag Res, 17, 1087–1097.
  • [23] Abd El-Aleam, R.H., Sayed, A.M., Taha, M.N., George, R.F., Georgey, H.H., Abdel- Rahman, H.M., (2022) Design and Synthesis of Novel Benzimidazole Derivatives as Potential Pseudomonas aeruginosa Anti-Biofilm Agents Inhibiting LasR: Evidence from Comprehensive Molecular Dynamics Simulation and in Vitro Investigation, Eur J Med Chem, 241, 114629.
  • [24] Schleser, S.W., Köhler, L.H.F., Riethmüller, F., Reich, S., Fertig, R., Schlotte, L., Seib, J., Goller, A., Begemann, G., Kempe, R., Schobert, R., (2023) Anti‐Tumoural [NHC(Thiolato)] Gold(I) Complexes Derived from HIF‐1α Inhibitor AC1‐004 Target the Mitochondrial Redox System and Show Antiangiogenic Effects in Vivo, Chempluschem, 88.
  • [25] Dighe, S.N., van Akker, S.R., Mathew, M., Perera, M., Collet, T.A., (2021) Discovery of a Novel Antimicrobial Agent by the Virtual Screening of a Library of Small Molecules, Mol Inform, 40.
  • [26] Hehir, S., O’Donovan, L., Carty, M.P., Aldabbagh, F., (2008) Synthesis of Dimethyl Substituted Benzimidazoles Containing Cyclopropane Fused onto Five to Eight Membered [1,2-a]Alicyclic Rings and Influence of Methyl Group Substituents on Cytotoxicity of Benzimidazolequinones, Tetrahedron, 64, 4196–4203.
  • [27] Neochoritis, C.G., Zarganes-Tzitzikas, T., Tsoleridis, C.A., Stephanidou-Stephanatou, J., Kontogiorgis, C.A., Hadjipavlou-Litina, D.J., Choli-Papadopoulou, T., (2011) One-Pot Microwave Assisted Synthesis under Green Chemistry Conditions, Antioxidant Screening, and Cytotoxicity Assessments of Benzimidazole Schiff Bases and Pyrimido[1,2-a]Benzimidazol- 3(4H)-Ones, Eur J Med Chem, 46, 297–306.
  • [28] Kumaravel, G., Ponya Utthra, P., Raman, N., (2018) Exploiting the Biological Efficacy of Benzimidazole Based Schiff Base Complexes with L-Histidine as a Co-Ligand: Combined Molecular Docking, DNA Interaction, Antimicrobial and Cytotoxic Studies, Bioorg Chem, 77, 269–279. [29] Dastyafteh, N., Negahdaripour, M., Sayahi, M.H., Emami, M., Ghasemi, Y., Safaei, E., Azizian, H., Pakrouh Jahromi, Z., Asadi, M., Mohajeri-Tehrani, M.R., Zare, F., Shahidi, M., Pooraskari, Z., Sajjadi-Jazi, S.M., Larijani, B., Mahdavi, M., Ranjbar, S., (2024) Design, Synthesis, Biological Evaluation, and in Silico Studies of Novel N-Substituted-2-(3,4,5- Trimethoxyphenyl)-1H-Benzo[d]Imidazole-6-Carboxamides as Promising Anticancer Agents, RSC Adv, 14, 35323–35335.
  • [30] Batooie, N., Khodaei, M.M., Bahrami, K., Miraghaee, S.S., Hosseinzadeh, N., Sajadimajd, S., (2023) One-Pot Synthesis of New Benzo[4,5]Imidazo[2,1-b]Pyrimido[4,5-d][1,3]Thiazine- 2,4(3H)-Dione and Benzo[4,5]Imidazo[2,1-b][1,3]Thiazin-4-One Derivatives as New Anti- Cancer Components, J Mol Struct, 1271, 134037.
  • [31] Gökoğlan, E., Dere, D., Bedir, İ., Yelekçi, K., Telci, D., Küçükgüzel, Ş.G., (2023) Synthesis and Investigation of Cytotoxic Effects of Compounds Derived from Flurbiprofen, J Mol Struct, 1289, 135876.
  • [32] Wang, X.; Liu, Y.; Liu, M.; Ren, G. (2021). Human skin fibroblast cell models in vitro for screening of skin irritation: a review. Toxicology in Vitro, 75, 105178.
  • [33] Schäfer, M.; Werner, S. (2007). Transcriptional control of wound repair. Annual Review of Cell and Developmental Biology, 23, 69–92.
  • [34] OECD (2004). Guidance Document on the Validation and International Acceptance of New or Updated Test Methods for Hazard Assessment. OECD Series on Testing and Assessment No. 34.
  • [35] El-Gohary, N.S., Shaaban, M.I., (2017) Synthesis, Antimicrobial, Antiquorum-Sensing and Antitumor Activities of New Benzimidazole Analogs, Eur J Med Chem, 137, 439–449.
  • [36] Çevik, U.A., Sağlık, B.N., Osmaniye, D., Levent, S., Çavuşoğlu, B.K., Karaduman, A.B., Eklioğlu, Ö.A., Özkay, Y., Kaplancıklı, Z.A., (2020) Synthesis, Anticancer Evaluation and Molecular Docking Studies of New Benzimidazole-1,3,4-oxadiazole Derivatives as Human Topoisomerase Types I Poison, J Enzyme Inhib Med Chem, 35, 1657–1673.
  • [37] Özkay, Y., Yurttaş, L., Dikmen, M., Engür, S., (2016) Synthesis and Antiproliferative Activity Evaluation of New Thiazole–Benzimidazole Derivatives Using Real-Time Cell Analysis (RTCA DP), Medicinal Chemistry Research, 25, 482–493.
  • [38] Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. (2008). Fluorine in medicinal chemistry. Chemical Society Reviews, 37(2), 320–330.
  • [39] Sun, S.; Fu, J. (2018). Methyl-containing pharmaceuticals: Methylation in drug design. Bioorg Med Chem Lett, 28(20), 3283–3289
  • [40] Kuzu, B., Yetkin, D., Hepokur, C., Algul, O., (2025) Pyrrole‐Tethered Bisbenzoxazole Derivatives: Apoptosis‐Inducing Agents Targeting Breast Cancer Cells, Chem Biol Drug Des, 105(3), e70078.

Impact of Heterocyclic Benzimidazole–Thioether Derivatives on the Proliferation of Human Dermal Fibroblast

Year 2025, Volume: 18 Issue: 2, 464 - 475, 31.08.2025
https://doi.org/10.18185/erzifbed.1726734

Abstract

Benzimidazole derivatives have attracted considerable attention in anticancer research due to their favorable pharmacological and physicochemical properties. However, data regarding their cytotoxicity and safety in normal (non-cancerous) cell lines are still limited. Therefore, in this study, the effect of heterocyclic benzimidazole-thioether compounds on the proliferation of Human Skin Fibroblast (HDFa) cell line was investigated at concentrations of 10 nM, 100 nM, 500 nM, 1 µM and for 24 and 48 hours. IC50 values for heterocyclic benzimidazole-thioether compounds 11 and 12 were found to be 117.93, 13.2 nM and 52.14, 28.2 nM for 24 and 48 hours, respectively. In the study, the closest viability concentrations to the control group for the 11 molecule among the heterocyclic benzimidazole-thioether compounds were found to be 10nm at 24 and 48 hours. In addition, while 500 nm and 1 µM were statistically significant at 24 hours for compound-11, 100 nm, 500 nm and 1 µM were statistically significant at 24 hours for compound-12, while all concentrations were statistically significant at 48 hours (p<0.05).

Ethical Statement

There are no ethical issues regarding the publication of this study

Supporting Institution

No funding was received for this study.

Project Number

-

Thanks

-

References

  • [1] Wright, J.B., (1951) The Chemistry of the Benzimidazoles, Chem Rev, 48 397–541.
  • [2] Bansal, Y., Kaur, M., Bansal, G., (2019) Antimicrobial Potential of Benzimidazole Derived Molecules, Mini-Reviews in Medicinal Chemistry, 19 624–646.
  • [3] Mendogralo, E.Y., Nesterova, L.Y., Nasibullina, E.R., Shcherbakov, R.O., Myasnikov, D.A., Tkachenko, A.G., Sidorov, R.Y., Uchuskin, M.G., (2023) Synthesis, Antimicrobial and Antibiofilm Activities, and Molecular Docking Investigations of 2-(1H-Indol-3-Yl)-1H- Benzo[d]Imidazole Derivatives, Molecules, 28 7095.
  • [4] Coelho, R.A., Figueiredo-Carvalho, M.H.G., Almeida-Silva, F., de Souza Rabello, V.B., de Souza, G.R., Sangenito, L.S., Joffe, L.S., Santos, A.L.S., da Silva Lourenço, M.C., Rodrigues, M.L., Almeida-Paes, R., (2023) Repurposing Benzimidazoles against Causative Agents of Chromoblastomycosis: Albendazole Has Superior In Vitro Activity Than Mebendazole and Thiabendazole, Journal of Fungi, 9 753.
  • [5] Sharma, A., Luxami, V., Paul, K., (2015) Purine-Benzimidazole Hybrids: Synthesis, Single Crystal Determination and in Vitro Evaluation of Antitumor Activities, Eur J Med Chem, 93 414–422.
  • [6] Sun, D., Wang, C., Fan, Y., Gu, J., (2023) Identification, Structure Elucidation and Origin of a Common Pyridinium-Thiocyanate Intermediate in Electrospray Mass Spectrometry among the Benziamidazole-Class Proton Pump Inhibitors, J Pharm Anal, 13 683–688.
  • [7] Choudhary, A., Viradiya, R.H., Ghoghari, R.N., Chikhalia, K.H., (2023) Recent Scenario for the Synthesis of Benzimidazole Moiety(2020–2022), ChemistrySelect, 8.
  • [8] Yadav, G., Ganguly, S., (2015) Structure Activity Relationship (SAR) Study of Benzimidazole Scaffold for Different Biological Activities: A Mini-Review, Eur J Med Chem, 97 419–443.
  • [9] Haider, K., Shahar Yar, M., (2022) Advances of Benzimidazole Derivatives as Anticancer Agents: Bench to Bedside. In S. Basak (Ed.), Benzimidazole derivatives (pp. 1–24). IntechOpen, United Kingdom.
  • [10] Aroua, L.M., (2020) Novel Mixed Complexes Derived from Benzoimidazolphenylethanamine and 4-(Benzoimidazol-2-Yl)Aniline: Synthesis, Characterization, Antibacterial Evaluation and Theoretical Prediction of Toxicity, Asian Journal of Chemistry, 32 1266–1272.
  • [11] Tayade, A.P., Pawar, R.P., (2022) The Microwave Assisted and Efficient Synthesis of 2- Substituted Benzimidazole Mono-Condensation of O-Phenylenediamines and Aldehyde, Polycycl Aromat Compd, 42(1), 1474–1478.
  • [12] Dokla, E.M.E., Abutaleb, N.S., Milik, S.N., Li, D., El-Baz, K., Shalaby, M.-A.W., Al- Karaki, R., Nasr, M., Klein, C.D., Abouzid, K.A.M., Seleem, M.N., (2020) Development of Benzimidazole-Based Derivatives as Antimicrobial Agents and Their Synergistic Effect with Colistin against Gram-Negative Bacteria, Eur J Med Chem, 186, 111850.
  • [13] Maghraby, M.T.-E., Abou-Ghadir, O.M.F., Abdel-Moty, S.G., Ali, A.Y., Salem, O.I.A., (2020) Novel Class of Benzimidazole-Thiazole Hybrids: The Privileged Scaffolds of Potent Anti-Inflammatory Activity with Dual Inhibition of Cyclooxygenase and 15-Lipoxygenase Enzymes, Bioorg Med Chem, 28(1), 115403.
  • [14] Imran, M., Al Kury, L.T., Nadeem, H., Shah, F.A., Abbas, M., Naz, S., Khan, A., Li, S., (2020) Benzimidazole Containing Acetamide Derivatives Attenuate Neuroinflammation and Oxidative Stress in Ethanol-Induced Neurodegeneration, Biomolecules, 10(1), 108.
  • [15] Doganc, F., Celik, I., Eren, G., Kaiser, M., Brun, R., Goker, H., (2021) Synthesis, in Vitro Antiprotozoal Activity, Molecular Docking and Molecular Dynamics Studies of Some New Monocationic Guanidinobenzimidazoles, Eur J Med Chem, 221, 113545.
  • [16] Choudhary, S., Arora, M., Verma, H., Kumar, M., Silakari, O., (2021) Benzimidazole Based Hybrids against Complex Diseases: A Catalogue of the SAR Profile, Eur J Pharmacol, 899, 174027.
  • [17] Miller, J.F., Turner, E.M., Gudmundsson, K.S., Jenkinson, S., Spaltenstein, A., Thomson, M., Wheelan, P., (2010) Novel N-Substituted Benzimidazole CXCR4 Antagonists as Potential Anti-HIV Agents, Bioorg Med Chem Lett, 20(7), 2125–2128.
  • [18] Pan, T., He, X., Chen, B., Chen, H., Geng, G., Luo, H., Zhang, H., Bai, C., (2015) Development of Benzimidazole Derivatives to Inhibit HIV-1 Replication through Protecting APOBEC3G Protein, Eur J Med Chem, 95, 500–513. [19] Singh, I., Luxami, V., Paul, K., (2019) Synthesis and in Vitro Evaluation of Naphthalimide–Benzimidazole Conjugates as Potential Antitumor Agents, Org Biomol Chem, 17(22), 5349–5366.
  • [20] Wang, Z., Deng, X., Xiong, R., Xiong, S., Liu, J., Cao, X., Lei, X., Chen, Y., Zheng, X., Tang, G., (2018) Design, Synthesis and Biological Evaluation of 3′,4′,5′-Trimethoxy Flavonoid Benzimidazole Derivatives as Potential Anti-Tumor Agents, Medchemcomm, 9(2), 305–315.
  • [21] Hranjec, M., Starčević, K., Pavelić, S.K., Lučin, P., Pavelić, K., Karminski Zamola, G., (2011) Synthesis, Spectroscopic Characterization and Antiproliferative Evaluation in Vitro of Novel Schiff Bases Related to Benzimidazoles, Eur J Med Chem, 46, 2274–2279.
  • [22] Radzikowska-Bűchner, E., Radej, S., Niezabitowska, E., Sitarz, R., Szewc, M., (2025) Potential of Using New Indole- and Benzimidazo[1,2-C]Quinazolines in Anticancer Therapy Based on Mesenchymal Stem Cells, Cancer Manag Res, 17, 1087–1097.
  • [23] Abd El-Aleam, R.H., Sayed, A.M., Taha, M.N., George, R.F., Georgey, H.H., Abdel- Rahman, H.M., (2022) Design and Synthesis of Novel Benzimidazole Derivatives as Potential Pseudomonas aeruginosa Anti-Biofilm Agents Inhibiting LasR: Evidence from Comprehensive Molecular Dynamics Simulation and in Vitro Investigation, Eur J Med Chem, 241, 114629.
  • [24] Schleser, S.W., Köhler, L.H.F., Riethmüller, F., Reich, S., Fertig, R., Schlotte, L., Seib, J., Goller, A., Begemann, G., Kempe, R., Schobert, R., (2023) Anti‐Tumoural [NHC(Thiolato)] Gold(I) Complexes Derived from HIF‐1α Inhibitor AC1‐004 Target the Mitochondrial Redox System and Show Antiangiogenic Effects in Vivo, Chempluschem, 88.
  • [25] Dighe, S.N., van Akker, S.R., Mathew, M., Perera, M., Collet, T.A., (2021) Discovery of a Novel Antimicrobial Agent by the Virtual Screening of a Library of Small Molecules, Mol Inform, 40.
  • [26] Hehir, S., O’Donovan, L., Carty, M.P., Aldabbagh, F., (2008) Synthesis of Dimethyl Substituted Benzimidazoles Containing Cyclopropane Fused onto Five to Eight Membered [1,2-a]Alicyclic Rings and Influence of Methyl Group Substituents on Cytotoxicity of Benzimidazolequinones, Tetrahedron, 64, 4196–4203.
  • [27] Neochoritis, C.G., Zarganes-Tzitzikas, T., Tsoleridis, C.A., Stephanidou-Stephanatou, J., Kontogiorgis, C.A., Hadjipavlou-Litina, D.J., Choli-Papadopoulou, T., (2011) One-Pot Microwave Assisted Synthesis under Green Chemistry Conditions, Antioxidant Screening, and Cytotoxicity Assessments of Benzimidazole Schiff Bases and Pyrimido[1,2-a]Benzimidazol- 3(4H)-Ones, Eur J Med Chem, 46, 297–306.
  • [28] Kumaravel, G., Ponya Utthra, P., Raman, N., (2018) Exploiting the Biological Efficacy of Benzimidazole Based Schiff Base Complexes with L-Histidine as a Co-Ligand: Combined Molecular Docking, DNA Interaction, Antimicrobial and Cytotoxic Studies, Bioorg Chem, 77, 269–279. [29] Dastyafteh, N., Negahdaripour, M., Sayahi, M.H., Emami, M., Ghasemi, Y., Safaei, E., Azizian, H., Pakrouh Jahromi, Z., Asadi, M., Mohajeri-Tehrani, M.R., Zare, F., Shahidi, M., Pooraskari, Z., Sajjadi-Jazi, S.M., Larijani, B., Mahdavi, M., Ranjbar, S., (2024) Design, Synthesis, Biological Evaluation, and in Silico Studies of Novel N-Substituted-2-(3,4,5- Trimethoxyphenyl)-1H-Benzo[d]Imidazole-6-Carboxamides as Promising Anticancer Agents, RSC Adv, 14, 35323–35335.
  • [30] Batooie, N., Khodaei, M.M., Bahrami, K., Miraghaee, S.S., Hosseinzadeh, N., Sajadimajd, S., (2023) One-Pot Synthesis of New Benzo[4,5]Imidazo[2,1-b]Pyrimido[4,5-d][1,3]Thiazine- 2,4(3H)-Dione and Benzo[4,5]Imidazo[2,1-b][1,3]Thiazin-4-One Derivatives as New Anti- Cancer Components, J Mol Struct, 1271, 134037.
  • [31] Gökoğlan, E., Dere, D., Bedir, İ., Yelekçi, K., Telci, D., Küçükgüzel, Ş.G., (2023) Synthesis and Investigation of Cytotoxic Effects of Compounds Derived from Flurbiprofen, J Mol Struct, 1289, 135876.
  • [32] Wang, X.; Liu, Y.; Liu, M.; Ren, G. (2021). Human skin fibroblast cell models in vitro for screening of skin irritation: a review. Toxicology in Vitro, 75, 105178.
  • [33] Schäfer, M.; Werner, S. (2007). Transcriptional control of wound repair. Annual Review of Cell and Developmental Biology, 23, 69–92.
  • [34] OECD (2004). Guidance Document on the Validation and International Acceptance of New or Updated Test Methods for Hazard Assessment. OECD Series on Testing and Assessment No. 34.
  • [35] El-Gohary, N.S., Shaaban, M.I., (2017) Synthesis, Antimicrobial, Antiquorum-Sensing and Antitumor Activities of New Benzimidazole Analogs, Eur J Med Chem, 137, 439–449.
  • [36] Çevik, U.A., Sağlık, B.N., Osmaniye, D., Levent, S., Çavuşoğlu, B.K., Karaduman, A.B., Eklioğlu, Ö.A., Özkay, Y., Kaplancıklı, Z.A., (2020) Synthesis, Anticancer Evaluation and Molecular Docking Studies of New Benzimidazole-1,3,4-oxadiazole Derivatives as Human Topoisomerase Types I Poison, J Enzyme Inhib Med Chem, 35, 1657–1673.
  • [37] Özkay, Y., Yurttaş, L., Dikmen, M., Engür, S., (2016) Synthesis and Antiproliferative Activity Evaluation of New Thiazole–Benzimidazole Derivatives Using Real-Time Cell Analysis (RTCA DP), Medicinal Chemistry Research, 25, 482–493.
  • [38] Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. (2008). Fluorine in medicinal chemistry. Chemical Society Reviews, 37(2), 320–330.
  • [39] Sun, S.; Fu, J. (2018). Methyl-containing pharmaceuticals: Methylation in drug design. Bioorg Med Chem Lett, 28(20), 3283–3289
  • [40] Kuzu, B., Yetkin, D., Hepokur, C., Algul, O., (2025) Pyrrole‐Tethered Bisbenzoxazole Derivatives: Apoptosis‐Inducing Agents Targeting Breast Cancer Cells, Chem Biol Drug Des, 105(3), e70078.
There are 38 citations in total.

Details

Primary Language English
Subjects Pharmaceutical Sciences
Journal Section Makaleler
Authors

Ayça Aktaş Şüküroğlu 0000-0003-3069-7905

Mine Buğa Aktekin 0000-0002-7208-5651

Project Number -
Early Pub Date August 14, 2025
Publication Date August 31, 2025
Submission Date June 25, 2025
Acceptance Date July 14, 2025
Published in Issue Year 2025 Volume: 18 Issue: 2

Cite

APA Aktaş Şüküroğlu, A., & Buğa Aktekin, M. (2025). Impact of Heterocyclic Benzimidazole–Thioether Derivatives on the Proliferation of Human Dermal Fibroblast. Erzincan University Journal of Science and Technology, 18(2), 464-475. https://doi.org/10.18185/erzifbed.1726734