2,5(6)-DİSÜBSTİTÜEBENZİMİDAZOL TÜREVİ LİGANDLARI TAŞIYAN PLATİN KOMPLEKSLERİNİN ANTİKANSER AKTİVİTELERİNİN ARAŞTIRILMASI

Year 2023, , 531 - 542, 20.05.2023

Yasmin Aljendy , Hatice Oruç Demirbağ , Gül Bayram , Semra Utku

https://doi.org/10.33483/jfpau.1239326

Abstract

Amaç: Sisplatin, klinikte kanser hastalarının tedavisinde başarılı bir şekilde kullanılmasına rağmen hastalarda rezistans gelişimi ve ciddi toksik yan etkiler görülmektedir. Bu dezavantajların önüne geçmek için bu çalışmada 2,5(6)-disübstitüebenzimidazol türevi taşıyıcı ligandlar kullanarak platin(II) komplekslerinin sentezlenmesi ve sitotoksik etkilerinin test edilmesi amaçlanmıştır.
Gereç ve Yöntem: L1-L6 taşıyıcı ligandları Philips yöntemine göre elde edilmiştir. K1-K4 kompleksleri, K2PtCl4 ve uygun ligandın ısıtılıp karıştırılması ile sentezlenmiştir. Sentez edilen L1-L6 ve K1-K4’ün kimyasal yapıları elementel analiz, İnfrared ve 1H Nükleer Manyetik Rezonans ile aydınlatılmıştır. L1-L6 taşıyıcı ligandları ve K1-K4 komplesklerinin, MTT yöntemi ile MCF-7 ve DU-145 hücre hatlarına karşı in vitro sitotoksik etkileri test edilmiştir.
Sonuç ve Tartışma: IC50 değerlerine göre 2 numaralı konumunda –CH3 sübstitüenti taşıyan ligandlar, nonsübstitüe ligandlara göre test edilen hücre hatlarında daha etkili bulunmuştur. Ayrıca 5(6) numaralı konumunda flor sübstitüe L5 ve L6 en etkili benzimidazol türevi olarak test edilmiştir. Test edilen kompleksler içerisinde K3, MCF-7 hücre hattına karşı 32.75 µM IC50 değeri ile DU-145 hücre hattında ise 18.842 µM IC50 değeri ile en etkili kompleks olarak bulunmuştur.

Keywords

Benzimidazol, platin(II)kompleksleri, sisplatin, sitotoksik aktivite

Supporting Institution

Mersin Üniversitesi Bilimsel Araştırma Projeleri birimi

Project Number

2019-3-TP2-3714

Thanks

.

INVESTIGATION OF THE ANTICANCER ACTIVITIES OF PLATIN COMPLEXES BEARING 2,5(6)-DISUBSTITUTEDBENZIMIDAZOLE DERIVATIVE LIGANDS

Abstract

Objective: Although cisplatin is used successfully in the treatment of cancer patients in the clinic, resistance development and serious toxic side effects are seen in patients. In order to avoid these disadvantages, in this study, it was aimed to synthesize platinum(II) complexes using 2,5(6)-disubstitutedbenzimidazole derivative carrier ligands and to test their cytotoxic effects.
Material and Method: L1-L6 carrier ligands were synthesized according to the Philips method. K1-K4 complexes were synthesized by heating and mixing K2PtCl4 and the appropriate ligand. The chemical structures of synthesized L1-L6 and K1-K4 were elucidated by elemental analysis, Infrared and 1H Nuclear Magnetic Resonance. In vitro cytotoxic effects of L1-L6 carrier ligands and K1-K4 complexes against MCF-7 and DU-145 cell lines were tested by MTT method.
Result and Discussion: Ligands with –CH3 substituent in position 2 according to IC50 values were found to be more effective in tested cell lines than non-substituted ligands. Also, fluorine substituted L5 and L6 at position 5(6) were tested as the most effective benzimidazole derivatives. Among the tested complexes, it was found to be the most effective complex with an IC50 value of 32.75 µM against the K3 MCF-7 cell line and with an IC50 value of 18.842 µM in the DU-145 cell line.

Keywords

Benzimidazole, cisplatin, cytotoxic activity, platinum(II)complexes

Project Number

2019-3-TP2-3714

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