Journals / International Journal of Secondary Metabolite / 2026 / Volume: 13 Issue: 2

Assessment of cytotoxicity and antitumor activity of newly developed compounds in A549 lung cancer cells

Osman Çiftçi(PAMUKKALE ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0001-5755-3560
Münevver Nazlıcan Kaplan(PAMUKKALE ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0002-3536-6606
Enes Evren(İNÖNÜ ÜNİVERSİTESİ)0000-0002-7571-410X
Fatma Nihan Cankara(SÜLEYMAN DEMİREL ÜNİVERSİTESİ)0000-0002-2367-6412
Pages
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Publication Date
2026-03-09
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

The newly synthesized Ag-NHC complexes (X, Y, Z) exhibited significant antiproliferative and pro-apoptotic effects in A549 lung cancer cells, indicating their potential as new therapeutic agents with reduced toxicity compared to conventional chemotherapy.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Lung cancer is among the most common cancers in the world, and current treatments are inadequate due to the development of resistance and serious side effects.
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Key Findings & Data:This situation brings new therapeutic strategies for cancer treatment.
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Conclusion & Impact:The newly synthesized Ag-NHC complexes (X, Y, Z) exhibited significant antiproliferative and pro-apoptotic effects in A549 lung cancer cells, indicating their potential as new therapeutic agents with reduced toxicity compared to conventional chemotherapy.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Ag-NHC · Apoptosis · Lung cancer

Abstract

Lung cancer is among the most common cancers in the world, and current treatments are inadequate due to the development of resistance and serious side effects. This situation brings new therapeutic strategies for cancer treatment. Among these, silver-based N-heterocyclic carbenes (Ag-NHCs) have emerged as promising candidates due to their unique chemical properties, such as strong metal-ligand bonding and modulation of biological reactivity. This study investigates the cytotoxic and antitumoral effects of newly synthesized Ag-NHC complexes on lung cancer (A549) cells. Ag-NHC complexes (X, Y, and Z) were synthesized using benzimidazolium salts and characterized by NMR spectroscopy. Cytotoxicity was evaluated on A549 and normal fibroblast (L929) cells using MTS assays. Apoptotic cell death and mitochondrial membrane potential were evaluated in A549 cells. Gene expression analysis for apoptosis-related markers was performed using RT-PCR. Ag-NHC complexes showed dose- and time-dependent antiproliferative effects in the A549 cell line. Annexin V/PI analysis revealed significant apoptotic induction by complexes X, Y and Z; the highest apoptotic rates were observed in A549 cells treated with Y and Z. Complexes Y and Z significantly decreased mitochondrial membrane potential, indicating increased apoptosis via intrinsic pathways. RT-PCR revealed increased pro-apoptotic gene expression (Bax, BAD, caspase-3, -8, -9) and decreased anti-apoptotic Bcl-2 expression in treated A549 cells. Complexes Y and Z also upregulated extrinsic apoptotic markers (DR4 and DR5). The newly synthesized Ag-NHC complexes (X, Y, Z) exhibited significant antiproliferative and pro-apoptotic effects in A549 lung cancer cells, indicating their potential as new therapeutic agents with reduced toxicity compared to conventional chemotherapy.

Özet

Lung cancer is among the most common cancers in the world, and current treatments are inadequate due to the development of resistance and serious side effects. This situation brings new therapeutic strategies for cancer treatment. Among these, silver-based N-heterocyclic carbenes (Ag-NHCs) have emerged as promising candidates due to their unique chemical properties, such as strong metal-ligand bonding and modulation of biological reactivity. This study investigates the cytotoxic and antitumoral effects of newly synthesized Ag-NHC complexes on lung cancer (A549) cells. Ag-NHC complexes (X, Y, and Z) were synthesized using benzimidazolium salts and characterized by NMR spectroscopy. Cytotoxicity was evaluated on A549 and normal fibroblast (L929) cells using MTS assays. Apoptotic cell death and mitochondrial membrane potential were evaluated in A549 cells. Gene expression analysis for apoptosis-related markers was performed using RT-PCR. Ag-NHC complexes showed dose- and time-dependent antiproliferative effects in the A549 cell line. Annexin V/PI analysis revealed significant apoptotic induction by complexes X, Y and Z; the highest apoptotic rates were observed in A549 cells treated with Y and Z. Complexes Y and Z significantly decreased mitochondrial membrane potential, indicating increased apoptosis via intrinsic pathways. RT-PCR revealed increased pro-apoptotic gene expression (Bax, BAD, caspase-3, -8, -9) and decreased anti-apoptotic Bcl-2 expression in treated A549 cells. Complexes Y and Z also upregulated extrinsic apoptotic markers (DR4 and DR5). The newly synthesized Ag-NHC complexes (X, Y, Z) exhibited significant antiproliferative and pro-apoptotic effects in A549 lung cancer cells, indicating their potential as new therapeutic agents with reduced toxicity compared to conventional chemotherapy.

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Cite This Article

Çiftçi, O., Kaplan, M. N., Evren, E., Cankara, F. N., Gürbüz, N., Özdemir, İ. (2026). Assessment of cytotoxicity and antitumor activity of newly developed compounds in A549 lung cancer cells. International Journal of Secondary Metabolite, Volume: 13 Issue: 2. https://doi.org/10.21448/ijsm.1754166

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References (19)

  1. Budagumpi, S., Haque, R.A., Endud, S., Rehman, G.U., & Salman, A.W. (2013). Biologically relevant silver(I)-N-heterocyclic carbene complexes: Synthesis, structure, intramolecular interactions, and applications. European Journal of Inorganic Chemistry, 2013(25), 4367 4388. https://doi.org/10.1002/ejic.201300483
  2. Collins, L.G., Haines, C., Perkel, R., & Enck, R.E. (2007). Lung cancer: Diagnosis and management. American Family Physician, 75(1), 56–63. PMID: 17225705.
  3. Crona, D.J., Faso, A., Nishijima, T.F., McGraw, K.A., Galsky, M.D., & Milowsky, M.I. (2017). A systematic review of strategies to prevent cisplatin-induced nephrotoxicity. The Oncologist, 22(5), 609–619. https://doi.org/10.1634/theoncologist.2016-0319
  4. Curtin, J. (2023). Advances in Diagnostic Tools and Therapeutic Approaches for Gliomas: A Comprehensive Review. https://doi.org/10.3390/s23249842
  5. Dasari, S., & Tchounwou, P.B. (2014). Cisplatin in cancer therapy: Molecular mechanisms of action. European Journal of Pharmacology, 740, 364–378. https://doi.org/10.1016/j.ejphar.2014.07.025
  6. Eloy, L., Jarrousse, A.S., Teyssot, M.L., Gautier, A., Morel, L., Jolivalt, C., et al. (2012). Anticancer activity of silver–N‐heterocyclic carbene complexes: Caspase‐independent induction of apoptosis via mitochondrial apoptosis inducing factor (AIF). ChemMedChem, 7(5), 805 814. https://doi.org/10.1002/cmdc.201200055
  7. Fabbrini, M.G., Cirri, D., Pratesi, A., Ciofi, L., Marzo, T., Guerri, A., et al. (2019). A fluorescent silver(I) carbene complex with anticancer properties: Synthesis, characterization, and biological studies. ChemMedChem, 14(1), 182–188. https://doi.org/10.1002/cmdc.201800672
  8. Fatima, T., Haque, R.A., Iqbal, M.A., Ahmad, A., Hassan, L.E.A., Taleb-Agha, M., et al. (2017). Tetra N-heterocyclic carbene dinuclear silver(I) complexes as potential anticancer agents: Synthesis and in vitro anticancer studies. Journal of Organometallic Chemistry, 853, 122–135. https://doi.org/10.1016/j.jorganchem.2017.10.045
  9. Gottesman, M.M., Fojo, T., & Bates, S.E. (2002). Multidrug resistance in cancer: Role of ATP-dependent transporters. Nature Reviews Cancer, 2(1), 48–58. https://doi.org/10.1038/nrc706
  10. Habib, A.V.M.N., Iqbal, M.A., Bhatti, H.N., Ahmed, M.B.K., & Majid, A.M.S.A. (2019). Unsymmetrically substituted benzimidazolium based silver(I)-N-heterocyclic carbene complexes: Synthesis, characterization and in vitro anticancer study against human breast cancer and colon cancer. Journal of Saudi Chemical Society, 23(7), 795 808. https://doi.org/10.1016/j.jscs.2019.03.002
  11. Iqbal, M.A., Umar, M.I., Haque, R.A., Ahamed, M.B.K., Asmawi, M.Z.B., & Majid, A.M.S.A. (2015). Macrophage and colon tumor cells as targets for a binuclear silver(I) N-heterocyclic carbene complex, an anti-inflammatory and apoptosis mediator. Journal of Inorganic Biochemistry, 146, 1–13. https://doi.org/10.1016/j.jinorgbio.2015.02.001
  12. Lipinski, C.A., Lombardo, F., Dominy, B.W., & Feeney, P.J. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 46(1–3), 3–26. https://doi.org/10.1016/S0169-409X(96)00423-1
  13. Nasim, F., Sabath, B.F., & Eapen, G.A. (2019). Lung cancer. Medical Clinics of North America, 103(3), 463–473. https://doi.org/10.1016/j.mcna.2018.12.006
  14. Özdemir, İ., Çiftçi, O., Evren, E., Gürbüz, N., Kaloğlu, N., Türkmen, N.B., et al. (2020). Synthesis, characterization and antitumor properties of novel silver(I) and gold(I) N-heterocyclic carbene complexes. Inorganica Chimica Acta, 506, 119530. https://doi.org/10.1016/j.ica.2020.119530
  15. Pfeffer, C.M., & Singh, A.T.K. (2018). Apoptosis: A target for anticancer therapy. International Journal of Molecular Sciences, 19(2), 448. https://doi.org/10.3390/ijms19020448
  16. Serdaroğlu, G., Şahin, N., Şahin-Bölükbaşı, S., & Üstün, E. (2022). Novel Ag(I)-NHC complex: Synthesis, in vitro cytotoxic activity, molecular docking, and quantum chemical studies. Zeitschrift für Naturforschung C, 77(1–2), 21–36. https://doi.org/10.1515/znc-2021-0130
  17. Teixeira, R.G., Brás, A.R., Côrte-Real, L., Tatikonda, R., Sanches, A., Robalo, M.P., et al. (2018). Novel ruthenium methylcyclopentadienyl complex bearing a bipyridine perfluorinated ligand shows strong activity towards colorectal cancer cells. European Journal of Medicinal Chemistry, 143, 503–514. https://doi.org/10.1016/j.ejmech.2017.11.059
  18. Visbal, R., & Gimeno, M.C. (2014). N-heterocyclic carbene metal complexes: Photoluminescence and applications. Chemical Society Reviews, 43(10), 3551–3574. https://doi.org/10.1039/C3CS60466G
  19. Zhao, Q., Han, B., Peng, C., Zhang, N., Huang, W., He, G., & Li, J.L. (2024). A promising future of metal–N‐heterocyclic carbene complexes in medicinal chemistry: The emerging bioorganometallic antitumor agents. Medicinal Research Reviews. Advance online publication. https://doi.org/10.1002/med.22132