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

Yıl 2024, Cilt: 48 Sayı: 3, 811 - 818, 10.09.2024

Tuğçe Yılmaz , Elif Ergin , Hatice Oruç Demirbağ , Semra Utku

https://doi.org/10.33483/jfpau.1461131

Öz

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.

Anahtar Kelimeler

1H-1,3-diazole, 1H-benzo[d]imidazole, cisplatin, cytotoxic activity, platinum complexes

Destekleyen Kurum

BAP

Proje Numarası

2022-1-TP2-4651

Teşekkür

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

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

Öz

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.

Anahtar Kelimeler

1H-1,3-diazol, 1H-benzo[d]imidazol, platin kompleksleri, sisplatin, sitotoksik aktivite

Proje Numarası

2022-1-TP2-4651

Kaynakça

• 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]