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IN VITRO CYTOTOXIC ACTIVITIES OF PLATINUM(II) COMPLEXES CONTAINING 1H-BENZO[d]IMIDAZOLE AND 1H-1,3-DIAZOLE DERIVATIVES

Year 2024, , 811 - 818, 10.09.2024
https://doi.org/10.33483/jfpau.1461131

Abstract

Objective: This study aimed to synthesize and evaluate the cytotoxic activities of four platinum(II) complexes with 2-substituted or nonsubstituted 1H-benzo[d]imidazole and 1H-1,3-diazole derivatives as carrier ligands (L1-L4), which may have potent cytotoxic activity and low side effects.
Material and Method: K1-K4 complexes were synthesized by heating and mixing K2PtCl4 and the appropriate L1-L4. The chemical structures of K1-K4 were elucidated by Infrared and 1H Nuclear Magnetic Resonance spectroscopic methods. In vitro, cytotoxic effects of K1-K4 complexes against prostate (DU-145), endometrial adenocarcinoma (Ishikawa), and breast cancer (MCF-7) cell lines were tested by the MTT method.
Result and Discussion: According to the IC50 values of the tested cell lines, K1 and K2 derivatives bearing unsubstituted 1H-benzo[d]imidazole (L1) and 1H-1,3-diazole (L2) were found to be the most effective compounds among these synthesized complexes.

Supporting Institution

BAP

Project Number

2022-1-TP2-4651

Thanks

This study was supported by Mersin University Scientific Research Projects Unit with project number 2022-1-TP2-4651.

References

  • 1. Wold Health Organization Web site. (2024). https://www.who.int/news/item/01-02-2024-global-cancer-burden-growing--amidst-mounting-need-for-services. Accessed date: 04.04.2024.
  • 2. Abbas, Z., Rehman, S. (2018). An Overview of Cancer Treatment Modalities. In: H.N. Shahzad (Ed.), Neoplasm, (pp. 139-157). London: IntechOpen.
  • 3. Ghosh, S. (2019). Cisplatin: The first metal based anticancer drug. Bioorganic Chemistry, 88, 102925. [CrossRef]
  • 4. Romani, A.M.P. (2022). Cisplatin in cancer treatment. Biochemical Pharmacology, 206, 115323. [CrossRef]
  • 5. Oun, R., Moussa, Y.E., Wheate, N.J. (2018). The side effects of platinum-based chemotherapy drugs: A review for chemists. Dalton Transactions, 47, 6645-6653. [CrossRef]
  • 6. Lugones, Y., Loren, P., Salazar, L.A. (2022). Cisplatin resistance: Genetic and epigenetic factors involved. Biomolecules, 12, 1365. [CrossRef]
  • 7. Galluzzi, L., Senovilla, L., Vitale, I., Michels, J., Martins, I., Kepp, O., Castedo, M., Kroemer, G. (2012). Molecular mechanisms of cisplatin resistance. Oncogene, 31, 1869-1883. [CrossRef]
  • 8. Johnstone, T.C., Suntharalingam, K., Lippard, S.J. (2016). The next generation of platinum drugs: Targeted Pt(II) agents, nanoparticle delivery, and Pt(IV) prodrugs. Chemical Reviews, 116, 3436-3486. [CrossRef]
  • 9. Bai, L., Gao, C., Liu, Q., Yu, C., Zhang, Z., Cai, L., Yang, B., Qian, Y., Yang, J., Liao, X. (2017). Research progress in modern structure of platinum complexes. European Journal of Medicinal Chemistry, 140, 349-382. [CrossRef]
  • 10. Kelland, L. (2007). The resurgence of platinum-based cancer chemotherapy. Nature Reviews Cancer, 7, 573–584. [CrossRef]
  • 11. Peng, K., Liang, B.B., Liu, W., Mao, Z.W. (2021). What blocks more anticancer platinum complexes from experiment to clinic: Major problems and potential strategies from drug design perspectives. Coordination Chemistry Reviews, 449, 214210. [CrossRef]
  • 12. Dasari, S., Bernard Tchounwou, P. (2014). Cisplatin in cancer therapy: Molecular mechanisms of action. European Journal of Pharmacology, 740, 364-378. [CrossRef]
  • 13. Sherman, S.E., Gibson, D., Wang, A.H.J., Lippard, S.J. (1985). X-ray structure of the major adduct of the anticancer drug cisplatin with DNA: Cis-[Pt(NH3)2{d(PGpG)}]. Science, 230, 412-417. [CrossRef]
  • 14. Calvert, H. (2019). The clinical development of carboplatin-A personal perspective. Inorganica Chimica Acta, 498, 118987. [CrossRef]
  • 15. Deo, K.M., Ang, D.L., McGhie, B., Rajamanickam, A., Dhiman, A., Khoury, A., Holland, J., Bjelosevic, A., Pages, B., Gordon, C., Aldrich-Wright, J.R. (2018). Coordination compounds with potent anticancer activity. Coordination Chemistry Reviews, 375, 148-163. [CrossRef]
  • 16. Brabec, V., Hrabina, O., Kasparkova, J. (2017). Cytotoxic platinum coordination compounds. DNA binding agents. Coordination Chemistry Reviews, 351, 2-31. [CrossRef]
  • 17. Utku, S., Gumus, F., Tezcan, S., Serin, M.S., Ozkul, A. (2010). Synthesis, characterization, cytotoxicity, and DNA binding of some new platinum(II) and platinum(IV) complexes with benzimidazole ligands. Journal of Enzyme Inhibition and Medicinal Chemistry, 25, 502-508. [CrossRef]
  • 18. Boğatarkan, Ç., Utku, S., Açik, L. (2015). Synthesis, characterization and Pbr322 plasmid DNA interaction of platinum(II) complexes with imidazole and 2-phenylimidazole as carrier ligands. Revue Roumaine de Chimie, 60, 59-64.
  • 19. Utku, S., Topal, M., Döğen, A., Serin, M.S. (2010) Synthesis, characterization, antibacterial and antifungal evaluation of some new platinum(II) complexes of 2-phenylbenzimidazole ligands. Turkish Journal of Chemistry, 34(3), 427-436. [CrossRef]
  • 20. Phillips, M.A. (1928). CCCXVII.-The formation of 2-substituted benziminazoles. Journal of the Chemical Society, 2393-2399. [CrossRef]
  • 21. International Standard. (2009). Biological evaluation of medical devices-Part 5 Test for in vitro cytotoxicity. http://nhiso.com/wp-content/uploads/2018/05/ISO-10993-5-2009.pdf. Accessed date: 04.06.2023.
  • 22. Ho, Y., Au‐Yeung, S.C.F., To, K.K.W. (2003). Platinum‐based anticancer agents: Innovative design strategies and biological perspectives. Medicinal Research Reviews, 23, 633-655. [CrossRef]
  • 23. Štarha, P., Křikavová, R. (2024). Platinum(IV) and platinum(II) anticancer complexes with biologically active releasable ligands. Coordination Chemistry Reviews, 501, 215578. [CrossRef]
  • 24. Ertuğrul, E.M., Özçelik, A.B., Çerçi, N.A., Açık, L., Utku, S. (2023). Synthesis, characterization, and in vitro cytotoxic activity of platinum(II) oxalato complexes involving 2-substitutedimidazole or 2-substitutedbenzimidazole derivatives as carrier ligands. İstanbul Journal of Pharmacy, 53, 308-313. [CrossRef]
  • 25. Aljendy, Y., Oruç Demirbağ, H., Bayram, G., Utku, S. (2023). 2,5(6)-Disübstitüebenzimidazol türevi ligandları taşıyan platin komplekslerinin antikanser aktivitelerinin araştırılması. Journal of Faculty of Pharmacy of Ankara University, 47(2), 21-21. [CrossRef]
  • 26. Özçelik, A.B., Utku, S., Gümüş, F., Keskin, A.Ç., Açık, L., Yılmaz, Ş., Özgüngör, A. (2012). Cytotoxicity and DNA interactions of some platinum(II) complexes with substituted benzimidazole ligands. Journal of Enzyme Inhibition and Medicinal Chemistry, 27, 413-418. [CrossRef]
  • 27. Yu, H., Gou, S., Wang, Z., Chen, F., Fang, L. (2016). Toward overcoming cisplatin resistance via sterically hindered platinum(II) complexes. European Journal of Medicinal Chemistry, 114, 141-152. [CrossRef]
  • 28. Zhang, H., Gou, S., Zhao, J., Chen, F., Xu, G., Liu, X. (2015). Cytotoxicity profile of novel sterically hindered platinum(II) complexes with (1R,2R)-N1,N2-dibutyl-1,2-diaminocyclohexane. European Journal of Medicinal Chemistry, 96, 187-195. [CrossRef]

1H-BENZO[d]İMİDAZOL VE 1H-1,3-DİAZOL TÜREVLERİ İÇEREN PLATİN(II) KOMPLEKSLERİNİN İN VİTRO SİTOTOKSİK AKTİVİTELERİ

Year 2024, , 811 - 818, 10.09.2024
https://doi.org/10.33483/jfpau.1461131

Abstract

Amaç: Bu çalışmada, güçlü sitotoksik aktiviteye ve düşük yan etkilere sahip olabilecek, taşıyıcı ligand olarak 2-sübstitüe veya nonsübstitüe 1H-benzo[d]imidazol ve 1H-1,3-diazol türevleri içeren dört platin(II) kompleksinin sentezlenmesi ve sitotoksik aktivitelerinin değerlendirilmesi amaçlanmıştır.
Gereç ve Yöntem: K1-K4 kompleksleri, K2PtCl4 ve uygun taşıyıcı ligandların ısıtılıp karıştırılmasıyla sentezlenmiştir. K1-K4'ün kimyasal yapıları Infrared ve 1H Nükleer Manyetik Rezonans spektroskopik yöntemleri ile aydınlatılmıştır. İn vitro olarak, K1-K4 komplekslerinin prostat (DU-145), endometrial adenokarsinom (Ishikawa) ve meme kanseri (MCF-7) hücre hatlarına karşı sitotoksik etkileri MTT yöntemi ile test edilmiştir.
Sonuç ve Tartışma: Test edilen hücre hatlarının IC50 değerlerine göre, sübstitüe olmayan 1H-benzo[d]imidazol veya 1H-1,3-diazol taşıyan K1 ve K2 türevlerinin sentezlenen bu kompleksler arasında en etkili bileşikler olduğu bulunmuştur.

Project Number

2022-1-TP2-4651

References

  • 1. Wold Health Organization Web site. (2024). https://www.who.int/news/item/01-02-2024-global-cancer-burden-growing--amidst-mounting-need-for-services. Accessed date: 04.04.2024.
  • 2. Abbas, Z., Rehman, S. (2018). An Overview of Cancer Treatment Modalities. In: H.N. Shahzad (Ed.), Neoplasm, (pp. 139-157). London: IntechOpen.
  • 3. Ghosh, S. (2019). Cisplatin: The first metal based anticancer drug. Bioorganic Chemistry, 88, 102925. [CrossRef]
  • 4. Romani, A.M.P. (2022). Cisplatin in cancer treatment. Biochemical Pharmacology, 206, 115323. [CrossRef]
  • 5. Oun, R., Moussa, Y.E., Wheate, N.J. (2018). The side effects of platinum-based chemotherapy drugs: A review for chemists. Dalton Transactions, 47, 6645-6653. [CrossRef]
  • 6. Lugones, Y., Loren, P., Salazar, L.A. (2022). Cisplatin resistance: Genetic and epigenetic factors involved. Biomolecules, 12, 1365. [CrossRef]
  • 7. Galluzzi, L., Senovilla, L., Vitale, I., Michels, J., Martins, I., Kepp, O., Castedo, M., Kroemer, G. (2012). Molecular mechanisms of cisplatin resistance. Oncogene, 31, 1869-1883. [CrossRef]
  • 8. Johnstone, T.C., Suntharalingam, K., Lippard, S.J. (2016). The next generation of platinum drugs: Targeted Pt(II) agents, nanoparticle delivery, and Pt(IV) prodrugs. Chemical Reviews, 116, 3436-3486. [CrossRef]
  • 9. Bai, L., Gao, C., Liu, Q., Yu, C., Zhang, Z., Cai, L., Yang, B., Qian, Y., Yang, J., Liao, X. (2017). Research progress in modern structure of platinum complexes. European Journal of Medicinal Chemistry, 140, 349-382. [CrossRef]
  • 10. Kelland, L. (2007). The resurgence of platinum-based cancer chemotherapy. Nature Reviews Cancer, 7, 573–584. [CrossRef]
  • 11. Peng, K., Liang, B.B., Liu, W., Mao, Z.W. (2021). What blocks more anticancer platinum complexes from experiment to clinic: Major problems and potential strategies from drug design perspectives. Coordination Chemistry Reviews, 449, 214210. [CrossRef]
  • 12. Dasari, S., Bernard Tchounwou, P. (2014). Cisplatin in cancer therapy: Molecular mechanisms of action. European Journal of Pharmacology, 740, 364-378. [CrossRef]
  • 13. Sherman, S.E., Gibson, D., Wang, A.H.J., Lippard, S.J. (1985). X-ray structure of the major adduct of the anticancer drug cisplatin with DNA: Cis-[Pt(NH3)2{d(PGpG)}]. Science, 230, 412-417. [CrossRef]
  • 14. Calvert, H. (2019). The clinical development of carboplatin-A personal perspective. Inorganica Chimica Acta, 498, 118987. [CrossRef]
  • 15. Deo, K.M., Ang, D.L., McGhie, B., Rajamanickam, A., Dhiman, A., Khoury, A., Holland, J., Bjelosevic, A., Pages, B., Gordon, C., Aldrich-Wright, J.R. (2018). Coordination compounds with potent anticancer activity. Coordination Chemistry Reviews, 375, 148-163. [CrossRef]
  • 16. Brabec, V., Hrabina, O., Kasparkova, J. (2017). Cytotoxic platinum coordination compounds. DNA binding agents. Coordination Chemistry Reviews, 351, 2-31. [CrossRef]
  • 17. Utku, S., Gumus, F., Tezcan, S., Serin, M.S., Ozkul, A. (2010). Synthesis, characterization, cytotoxicity, and DNA binding of some new platinum(II) and platinum(IV) complexes with benzimidazole ligands. Journal of Enzyme Inhibition and Medicinal Chemistry, 25, 502-508. [CrossRef]
  • 18. Boğatarkan, Ç., Utku, S., Açik, L. (2015). Synthesis, characterization and Pbr322 plasmid DNA interaction of platinum(II) complexes with imidazole and 2-phenylimidazole as carrier ligands. Revue Roumaine de Chimie, 60, 59-64.
  • 19. Utku, S., Topal, M., Döğen, A., Serin, M.S. (2010) Synthesis, characterization, antibacterial and antifungal evaluation of some new platinum(II) complexes of 2-phenylbenzimidazole ligands. Turkish Journal of Chemistry, 34(3), 427-436. [CrossRef]
  • 20. Phillips, M.A. (1928). CCCXVII.-The formation of 2-substituted benziminazoles. Journal of the Chemical Society, 2393-2399. [CrossRef]
  • 21. International Standard. (2009). Biological evaluation of medical devices-Part 5 Test for in vitro cytotoxicity. http://nhiso.com/wp-content/uploads/2018/05/ISO-10993-5-2009.pdf. Accessed date: 04.06.2023.
  • 22. Ho, Y., Au‐Yeung, S.C.F., To, K.K.W. (2003). Platinum‐based anticancer agents: Innovative design strategies and biological perspectives. Medicinal Research Reviews, 23, 633-655. [CrossRef]
  • 23. Štarha, P., Křikavová, R. (2024). Platinum(IV) and platinum(II) anticancer complexes with biologically active releasable ligands. Coordination Chemistry Reviews, 501, 215578. [CrossRef]
  • 24. Ertuğrul, E.M., Özçelik, A.B., Çerçi, N.A., Açık, L., Utku, S. (2023). Synthesis, characterization, and in vitro cytotoxic activity of platinum(II) oxalato complexes involving 2-substitutedimidazole or 2-substitutedbenzimidazole derivatives as carrier ligands. İstanbul Journal of Pharmacy, 53, 308-313. [CrossRef]
  • 25. Aljendy, Y., Oruç Demirbağ, H., Bayram, G., Utku, S. (2023). 2,5(6)-Disübstitüebenzimidazol türevi ligandları taşıyan platin komplekslerinin antikanser aktivitelerinin araştırılması. Journal of Faculty of Pharmacy of Ankara University, 47(2), 21-21. [CrossRef]
  • 26. Özçelik, A.B., Utku, S., Gümüş, F., Keskin, A.Ç., Açık, L., Yılmaz, Ş., Özgüngör, A. (2012). Cytotoxicity and DNA interactions of some platinum(II) complexes with substituted benzimidazole ligands. Journal of Enzyme Inhibition and Medicinal Chemistry, 27, 413-418. [CrossRef]
  • 27. Yu, H., Gou, S., Wang, Z., Chen, F., Fang, L. (2016). Toward overcoming cisplatin resistance via sterically hindered platinum(II) complexes. European Journal of Medicinal Chemistry, 114, 141-152. [CrossRef]
  • 28. Zhang, H., Gou, S., Zhao, J., Chen, F., Xu, G., Liu, X. (2015). Cytotoxicity profile of novel sterically hindered platinum(II) complexes with (1R,2R)-N1,N2-dibutyl-1,2-diaminocyclohexane. European Journal of Medicinal Chemistry, 96, 187-195. [CrossRef]
There are 28 citations in total.

Details

Primary Language English
Subjects Pharmaceutical Chemistry
Journal Section Research Article
Authors

Tuğçe Yılmaz 0000-0002-6561-1131

Elif Ergin 0000-0001-5014-9143

Hatice Oruç Demirbağ 0000-0002-1086-713X

Semra Utku 0000-0003-3181-9134

Project Number 2022-1-TP2-4651
Early Pub Date July 8, 2024
Publication Date September 10, 2024
Submission Date April 5, 2024
Acceptance Date April 24, 2024
Published in Issue Year 2024

Cite

APA Yılmaz, T., Ergin, E., Oruç Demirbağ, H., Utku, S. (2024). IN VITRO CYTOTOXIC ACTIVITIES OF PLATINUM(II) COMPLEXES CONTAINING 1H-BENZO[d]IMIDAZOLE AND 1H-1,3-DIAZOLE DERIVATIVES. Journal of Faculty of Pharmacy of Ankara University, 48(3), 811-818. https://doi.org/10.33483/jfpau.1461131
AMA Yılmaz T, Ergin E, Oruç Demirbağ H, Utku S. IN VITRO CYTOTOXIC ACTIVITIES OF PLATINUM(II) COMPLEXES CONTAINING 1H-BENZO[d]IMIDAZOLE AND 1H-1,3-DIAZOLE DERIVATIVES. Ankara Ecz. Fak. Derg. September 2024;48(3):811-818. doi:10.33483/jfpau.1461131
Chicago Yılmaz, Tuğçe, Elif Ergin, Hatice Oruç Demirbağ, and Semra Utku. “IN VITRO CYTOTOXIC ACTIVITIES OF PLATINUM(II) COMPLEXES CONTAINING 1H-BENZO[d]IMIDAZOLE AND 1H-1,3-DIAZOLE DERIVATIVES”. Journal of Faculty of Pharmacy of Ankara University 48, no. 3 (September 2024): 811-18. https://doi.org/10.33483/jfpau.1461131.
EndNote Yılmaz T, Ergin E, Oruç Demirbağ H, Utku S (September 1, 2024) IN VITRO CYTOTOXIC ACTIVITIES OF PLATINUM(II) COMPLEXES CONTAINING 1H-BENZO[d]IMIDAZOLE AND 1H-1,3-DIAZOLE DERIVATIVES. Journal of Faculty of Pharmacy of Ankara University 48 3 811–818.
IEEE T. Yılmaz, E. Ergin, H. Oruç Demirbağ, and S. Utku, “IN VITRO CYTOTOXIC ACTIVITIES OF PLATINUM(II) COMPLEXES CONTAINING 1H-BENZO[d]IMIDAZOLE AND 1H-1,3-DIAZOLE DERIVATIVES”, Ankara Ecz. Fak. Derg., vol. 48, no. 3, pp. 811–818, 2024, doi: 10.33483/jfpau.1461131.
ISNAD Yılmaz, Tuğçe et al. “IN VITRO CYTOTOXIC ACTIVITIES OF PLATINUM(II) COMPLEXES CONTAINING 1H-BENZO[d]IMIDAZOLE AND 1H-1,3-DIAZOLE DERIVATIVES”. Journal of Faculty of Pharmacy of Ankara University 48/3 (September 2024), 811-818. https://doi.org/10.33483/jfpau.1461131.
JAMA Yılmaz T, Ergin E, Oruç Demirbağ H, Utku S. IN VITRO CYTOTOXIC ACTIVITIES OF PLATINUM(II) COMPLEXES CONTAINING 1H-BENZO[d]IMIDAZOLE AND 1H-1,3-DIAZOLE DERIVATIVES. Ankara Ecz. Fak. Derg. 2024;48:811–818.
MLA Yılmaz, Tuğçe et al. “IN VITRO CYTOTOXIC ACTIVITIES OF PLATINUM(II) COMPLEXES CONTAINING 1H-BENZO[d]IMIDAZOLE AND 1H-1,3-DIAZOLE DERIVATIVES”. Journal of Faculty of Pharmacy of Ankara University, vol. 48, no. 3, 2024, pp. 811-8, doi:10.33483/jfpau.1461131.
Vancouver Yılmaz T, Ergin E, Oruç Demirbağ H, Utku S. IN VITRO CYTOTOXIC ACTIVITIES OF PLATINUM(II) COMPLEXES CONTAINING 1H-BENZO[d]IMIDAZOLE AND 1H-1,3-DIAZOLE DERIVATIVES. Ankara Ecz. Fak. Derg. 2024;48(3):811-8.

Kapsam ve Amaç

Ankara Üniversitesi Eczacılık Fakültesi Dergisi, açık erişim, hakemli bir dergi olup Türkçe veya İngilizce olarak farmasötik bilimler alanındaki önemli gelişmeleri içeren orijinal araştırmalar, derlemeler ve kısa bildiriler için uluslararası bir yayım ortamıdır. Bilimsel toplantılarda sunulan bildiriler supleman özel sayısı olarak dergide yayımlanabilir. Ayrıca, tüm farmasötik alandaki gelecek ve önceki ulusal ve uluslararası bilimsel toplantılar ile sosyal aktiviteleri içerir.