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

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

Article Details

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

Authors:

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

Publisher:

Ankara University

Main Topics:

Eczacılık ve İlaç Bilimleri

Journal:

Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.47 Issue 2, pp.531-542

Document Type:

Article

Publication Date:

5/2023

Document Language:

Turkish

Document ID (Org No.):

2001282831

pISSN:

1015-3918

Keywords:

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 platinumII complexes using 2,56-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 56 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.

 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 platinumII complexes using 2,56-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 56 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.

 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 platinumII complexes using 2,56-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 56 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.

 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 2,56-disübstitüebenzimidazol türevi taşıyıcı ligandlar kullanarak platinII 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-K4ün 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 56 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.

Article Details

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

Authors:

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

Publisher:

Ankara University

Main Topics:

Eczacılık ve İlaç Bilimleri

Journal:

Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.47 Issue 2, pp.531-542

Document Type:

Article

Publication Date:

5/2023

Document Language:

Turkish

Document ID (Org No.):

2001282831

pISSN:

1015-3918

Benzimidazole

cisplatin

cytotoxic activity

platinum(II)complexes

Benzimidazol

platin(II)kompleksleri

sisplatin

sitotoksik aktivite

Issues

Article Details

Authors: Yasmin Aljendy | Hatice Oruç Demirbağ | Gül Bayram | Semra Utku

Publisher: Ankara University

Main Topics: Eczacılık ve İlaç Bilimleri

Journal: Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.47 Issue 2, pp.531-542

Document Type: Article

Publication Date: 5/2023

Document Language: Turkish

Document ID (Org No.): 2001282831

pISSN: 1015-3918

Issues

Authors:

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

Publisher:

Ankara University

Main Topics:

Eczacılık ve İlaç Bilimleri

Journal:

Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.47 Issue 2, pp.531-542

Document Type:

Article

Publication Date:

5/2023

Document Language:

Turkish

Document ID (Org No.):

2001282831

pISSN:

1015-3918