Synthesis of 2-Substitutedbenzimidazolium Tetrachloroplatinate(II) Compounds and Their Cytotoxic Activities on Different Cell Lines
Yıl: 2022 Cilt: 47 Sayı: 3 Sayfa Aralığı: 281 - 292 Metin Dili: İngilizce DOI: 10.55262/fabadeczacilik.1134520 İndeks Tarihi: 25-11-2022
Synthesis of 2-Substitutedbenzimidazolium Tetrachloroplatinate(II) Compounds and Their Cytotoxic Activities on Different Cell Lines
Öz: The aim of the study was the synthesis of novel platinum compounds having benzimidazole ligands and screening for their in vitro cytotoxic activity on human cervical carcinoma HeLa, human lung carcinoma A549, and human lung epithelial Beas-2B cell lines. 2-Substituted benzimidazole ligands were synthesized by using appropriate aldehydes and o-phenylenediamine. Subsequently, 2-substituted benzimidazole ligands and potassium tetrachloroplatinate(II) (K2 PtCl4 ) were used to synthesize 2-isopropylbenzimidazole tetrachloroplatinate(II) (K1) and 2-(1-methylpropyl)benzimidazole tetrachloroplatinate(II) monohydrate (K2). HRMS, IR, elemental analysis, 1 H-NMR, and melting point were used to characterize the synthesized compounds. Cytotoxic activities against HeLa, A549, and Beas-2B cells after 48 h and 72 h incubation of the platinum compounds were investigated via MTT assay. Cisplatin and carboplatin were used as reference drugs. The cytotoxic activity results showed that K2 platinum compound displayed 53.42%±2.21 (at 160 μM) on HeLa, 88.16%±0.22 (at 160 μM) on A549 and 92.09%±0.57 (at 160 μM) on Beas-2B after 48 h incubation, K2 displayed 27.42%±2.03 (at 160 μM) on HeLa, 93.95%±0.53 (at 160 μM) on A549 and 91.99±0.22 (at 160 μM) on Beas-2B after 72 h incubation. Both of the platinum compounds have higher cell inhibitory effects than reference drug carboplatin after 48 h incubation for tested cells.
Anahtar Kelime: Sübstitüebenzimidazolyum Tetrakloroplatinat(II) Bileşiklerinin Sentezi ve Çeşitli Hücre Hatlarındaki Sitotoksik Etkileri
Öz: Bu çalışmanın amacı, benzimidazol ligandı taşıyan yeni platin bileşiklerinin sentezi ve bu bileşiklerin insan servikal karsinoma HeLa, insan akciğer karsinoma A549 ve insan sağlıklı akciğer epitel Beas-2B hücre hatları üzerindeki in vitro sitotoksik etkilerinin araştırılmasıdır. 2-Sübstitüe benzimidazol ligandları uygun aldehit türevleri ve o-fenilendiamin kullanılarak sentezlenmiştir. Ardından, 2-sübstitüe benzimidazol ligandları ve potasyum tetrakloroplatinat(II) (K2PtCl4) kullanılarak 2-izopropilbenzimidazol tetrakloroplatinat(II) (K1) and 2-(1-metilpropil)benzimidazol tetrakloroplatinat(II) monohidrate (K2) sentezlenmiştir. Sentezlenen bileşikler HRMS, IR, elementel analiz, 1H-NMR ve erime noktası kullanılarak karakterize edilmiştir. Sentezlenen platin bileşiklerinin HeLa, A549 ve Beas-2B hücre hatlarına karşı MTT testi kullanılarak sitotoksik etkileri araştırılmıştır. Referans ilaç olarak sisplatin ve karboplatin kullanılmıştır. Sitotoksik aktivite çalışmalarında, bileşik K2’nin 160 μM konsantrasyonda 48 saatlik inkübasyonları sonrasında inhibisyon değerleri HeLa hucrelerinde %53.42±2.21, A549 hucrelerinde %88.16±0.22 ve Beas-2B hucrelerinde %92.09±0.57 bulunmuştur. Her iki platin bileşiğinin de test edilen hücrelere karşı 48 saat inkübasyon sonucunda referans ilaç olan karboplatine göre daha etkili olduğu görülmüştür.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- Al-Khathami, N. D., Al-Rashdi, K. S., Babgi, B. A., Hussien, M. A., Nadeem Arshad, M., Eltayeb, N. E., Elsilk, S. E., Lasri, J., Basaleh, A. S., & Al-Jah- dali, M. (2019). Spectroscopic and biological properties of platinum complexes derived from 2-pyridyl Schiff bases. Journal of Saudi Chemical Society, 23(7), 903-915. https://doi.org/10.1016/j. jscs.2019.03.004
- Beltran-Hortelano, I., Alcolea, V., Font, M., & Pérez-Silanes, S. (2020). The role of imidazole and benzimidazole heterocycles in Chagas disease: A review. European Journal of Medicinal Chem- istry, 206, 112692. https://doi.org/10.1016/j.ej- mech.2020.112692
- Biersack, B. (2017). Interactions between anticancer active platinum complexes and non-coding RNAs/ microRNAs. Non-coding RNA Research, 2(1), 1-17. https://doi.org/10.1016/j.ncrna.2016.10.001
- Dasari, S., & Bernard Tchounwou, P. (2014). Cisplatin in cancer therapy: Molecular mechanisms of ac- tion. European Journal of Pharmacology, 740, 364- 378. https://doi.org/10.1016/j.ejphar.2014.07.025
- Daugaard, G., & Abildgaard, U. (1989). Cisplatin nephrotoxicity. A review. Cancer Chemother- apy and Pharmacology, 25(1), 1-9. https://doi. org/10.1007/bf00694330
- Doğan, U., Özcan, Ö., Alaca, G., Arı, A., Günnaz, S., Yalçın, H. T., Şahin, O., & İrişli, S. (2021). Novel Benzimidazole- Platinum(II) Complexes: Syn- thesis, Characterization, Antimicrobial and An- ticancer Activity. Journal of Molecular Structure, 1229, 129785. https://doi.org/10.1016/j.mol- struc.2020.129785
- Eren, G., Emerce, E., Acik, L., Aydin, B., & Gumus, F. (2019). A novel Trans-Pt(II) complex bearing 2-acetoxymethylbenzimidazole as a non-leaving ligand (trans-[Pt(AMBi)2Cl2]): Synthesis, anti- proliferative activity, DNA interaction and molec- ular docking studies compared with its cis isomer (cis-[Pt(AMBi)2Cl2]). Journal of Molecular Struc- ture, 1184, 512-518. https://doi.org/10.1016/j.mol- struc.2019.02.066
- Eren, G., Yilmaz, S., & Gumus, F. (2018). In Vitro Cytotoxic Activities of Platinum(II) Complex with 1-Methyl-2-(3’- hydroxypropyl)benzimid- azole and 2-(3’-Hydroxypropyl)benzimidazolium Hexa- and Tetrachloroplatinate Salts. Letters in Drug Design & Discovery, 15(1), 65-69. http://doi. org/10.2174/1570180814666
- Facchetti, G., & Rimoldi, I. (2019). Anticancer plat- inum(II) complexes bearing N-heterocycle rings. Bioorganic & Medicinal Chemistry Letters, 29(11), 1257-1263. https://doi.org/10.1016/j. bmcl.2019.03.045
- Gaba, M., & Mohan, C. (2016). Development of drugs based on imidazole and benzimidazole bioactive heterocycles: recent advances and future direc- tions. Medicinal Chemistry Research, 25(2), 173- 210. https://doi.org/10.1007/s00044-015-1495-5
- Ghosh, S. (2019). Cisplatin: The first metal based an- ticancer drug. Bioorganic Chemistry, 88, 102925. https://doi.org/10.1016/j.bioorg.2019.102925
- Gozelle, M., Kılıç Süloğlu, A., Selmanoğlu, G., Ra- mazanoğlu, N., Açık, L., & Gümüş, F. (2019). Studies on the synthesis, characterization, cyto- toxic activities and plasmid DNA binding of plat- inum(II) complexes having 2-subsituted benzim- idazole ligands. Polyhedron, 161, 298-308. https:// doi.org/10.1016/j.poly.2019.01.028
- Gümüş, F., Eren, G., Açık, L., Çelebi, A., Öztürk, F., Yılmaz, Ş., Saǧkan, R. I., Gür, S., Özkul, A., El- malı, A., & Elerman, Y. (2009). Synthesis, Cyto- toxicity, and DNA Interactions of New Cisplatin Analogues Containing Substituted Benzimidazole Ligands. Journal of Medicinal Chemistry, 52(5), 1345-1357. https://doi.org/10.1021/jm8000983
- Jamieson, E. R., & Lippard, S. J. (1999). Structure, Recognition, and Processing of Cisplatin−DNA Adducts. Chemical Reviews, 99(9), 2467-2498. https://doi.org/10.1021/cr980421n
- Mitra, I., Mukherjee, S., Reddy B, V. P., Dasgupta, S., Bose K, J. C., Mukherjee, S., Linert, W., & Moi, S. C. (2016). Benzimidazole based Pt(ii) complex- es with better normal cell viability than cispla- tin: synthesis, substitution behavior, cytotoxicity, DNA binding and DFT study. RSC Advances, 6(80), 76600-76613. https://doi.org/10.1039/ C6RA17788C
- Narasimhan, B., Sharma, D., & Kumar, P. (2012). Ben- zimidazole: a medicinally important heterocyclic moiety. Medicinal Chemistry Research, 21(3), 269- 283. https://doi.org/10.1007/s00044-010-9533-9
- Nashaat, S., Henen, M. A., El-Messery, S. M., & Eisa, H. (2020). Synthesis, state-of-the-art NMR-bind- ing and molecular modeling study of new benzim- idazole core derivatives as Pin1 inhibitors: Target- ing breast cancer. Bioorganic & Medicinal Chem- istry, 28(11), 115495. https://doi.org/10.1016/j. bmc.2020.115495
- Niknam, F., Hamidizadeh, P., Nabavizadeh, S. M., Niroomand Hosseini, F., Hoseini, S. J., Ford, P. C., & Abu-Omar, M. M. (2019). Synthesis, structur- al characterization, and luminescence properties of mono- and di-nuclear platinum(II) complexes containing 2-(2-pyridyl)-benzimidazole. Inor- ganica Chimica Acta, 498, 119133. https://doi. org/10.1016/j.ica.2019.119133
- Özçelik, A. B., Gümüş, F., Ilıkçı Sağkan, R., & Muşabak, U. (2015). Synthesis of platinum(II) complexes of 2-cycloalkyl-substituted benzimid- azoles and their cytotoxic effects. Zeitschrift für Naturforschung C, 70(9-10), 243-250. https://doi. org/10.1515/znc-2014-4188
- Özçelik, A. B., Gümüş, F., Kılıç Süloğlu, A., & Sel- manoğlu, G. (2019). Cytotoxic Activity Studies of Some Platinum(II) Complexes with 2-Substi- tutedbenzimidazole Ligands. Revue Roumaine de Chimie, 64(9), 829-834. https://doi.org/10.33224/ rrch.2019.64.9.10
- Özçelik, A. B., Utku, S., Gümüş, F., Keskin, A. Ç., Açık, L., Yılmaz, Ş., & Özgüngör, A. (2012). Cytotoxicity and DNA interactions of some plat- inum(II) complexes with substituted benzimidaz- ole ligands. Journal of Enzyme Inhibition and Me- dicinal Chemistry, 27(3), 413-418. https://doi.org/ 10.3109/14756366.2011.594046
- Pérez, J. M., López-Solera, I., Montero, E. I., Braña, M. F., Alonso, C., Robinson, S. P., & Navarro-Ran- ninger, C. (1999). Combined Effect of Platination and Intercalation upon DNA Binding of Novel Cytotoxic Pt−Bis(naphthalimide) Complexes. Journal of Medicinal Chemistry, 42(26), 5482- 5486. https://doi.org/10.1021/jm991099r
- Rosenberg, B., Van Camp, L., & Krigas, T. (1965). Inhibition of Cell Division in Escherichia coli by Electrolysis Products from a Platinum Electrode [10.1038/205698a0]. Nature, 205(4972), 698-699. http://doi.org/10.1038/205698a0
- Rosenberg, B., Van Camp, L., Trosko, J. E., & Mansour, V. H. (1969). Platinum compounds: a new class of potent antitumour agents. Nature, 222(5191), 385- 386. https://doi.org/10.1038/222385a0
- Utku, S., Gumus, F., Tezcan, S., Serin, M. S., & Ozkul, A. (2010). Synthesis, characterization, cytotoxic- ity, and DNA binding of some new platinum(II) and platinum(IV) complexes with benzimid- azole ligands. Journal of Enzyme Inhibition and Medicinal Chemistry, 25(4), 502-508. https://doi. org/10.3109/14756360903282858
- Utku, S., Özçelik, A. B., Gümüş, F., Yılmaz, Ş., Arsoy, T., Açık, L., & Çelebi Keskin, A. (2014). Synthesis, in-vitro cytotoxic activity and DNA interactions of new dicarboxylatoplatinum(II) complexes with 2-hydroxymethylbenzimidazole as carrier ligands. Journal of Pharmacy and Pharmacology, 66(11), 1593-1605. https://doi.org/10.1111/jphp.12290
- WHO. (2019). Cancer: Overview, prevention and management. Retrieved 21.04.2021 from https:// www.who.int/health-topics/cancer
- WHO. (2020). Human papillomavirus (HPV) and cer- vical cancer. Retrieved 21.04.2021 from https:// www.who.int/news-room/fact-sheets/detail/hu- man-papillomavirus-(hpv)-and-cervical-cancer
- Zeyrek, C. T., Unver, H., Gozelle, M., Dilek, N., & Gumus, F. (2017). Synthesis, Crystal Structure, Spectroscopic and Density Functional Modelling Studies of The 2-Isopropylbenzimidazolium Tet- rachloroplatinate(II) Monohydrate. Gazi Universi- ty Journal of Science, 30(1), 139-159.
| APA | Gozelle M, Kılıç Süloğlu A (2022). Synthesis of 2-Substitutedbenzimidazolium Tetrachloroplatinate(II) Compounds and Their Cytotoxic Activities on Different Cell Lines. , 281 - 292. 10.55262/fabadeczacilik.1134520 |
| Chicago | Gozelle Mahmut,Kılıç Süloğlu Aysun Synthesis of 2-Substitutedbenzimidazolium Tetrachloroplatinate(II) Compounds and Their Cytotoxic Activities on Different Cell Lines. (2022): 281 - 292. 10.55262/fabadeczacilik.1134520 |
| MLA | Gozelle Mahmut,Kılıç Süloğlu Aysun Synthesis of 2-Substitutedbenzimidazolium Tetrachloroplatinate(II) Compounds and Their Cytotoxic Activities on Different Cell Lines. , 2022, ss.281 - 292. 10.55262/fabadeczacilik.1134520 |
| AMA | Gozelle M,Kılıç Süloğlu A Synthesis of 2-Substitutedbenzimidazolium Tetrachloroplatinate(II) Compounds and Their Cytotoxic Activities on Different Cell Lines. . 2022; 281 - 292. 10.55262/fabadeczacilik.1134520 |
| Vancouver | Gozelle M,Kılıç Süloğlu A Synthesis of 2-Substitutedbenzimidazolium Tetrachloroplatinate(II) Compounds and Their Cytotoxic Activities on Different Cell Lines. . 2022; 281 - 292. 10.55262/fabadeczacilik.1134520 |
| IEEE | Gozelle M,Kılıç Süloğlu A "Synthesis of 2-Substitutedbenzimidazolium Tetrachloroplatinate(II) Compounds and Their Cytotoxic Activities on Different Cell Lines." , ss.281 - 292, 2022. 10.55262/fabadeczacilik.1134520 |
| ISNAD | Gozelle, Mahmut - Kılıç Süloğlu, Aysun. "Synthesis of 2-Substitutedbenzimidazolium Tetrachloroplatinate(II) Compounds and Their Cytotoxic Activities on Different Cell Lines". (2022), 281-292. https://doi.org/10.55262/fabadeczacilik.1134520 |
| APA | Gozelle M, Kılıç Süloğlu A (2022). Synthesis of 2-Substitutedbenzimidazolium Tetrachloroplatinate(II) Compounds and Their Cytotoxic Activities on Different Cell Lines. FABAD Journal of Pharmaceutical Sciences, 47(3), 281 - 292. 10.55262/fabadeczacilik.1134520 |
| Chicago | Gozelle Mahmut,Kılıç Süloğlu Aysun Synthesis of 2-Substitutedbenzimidazolium Tetrachloroplatinate(II) Compounds and Their Cytotoxic Activities on Different Cell Lines. FABAD Journal of Pharmaceutical Sciences 47, no.3 (2022): 281 - 292. 10.55262/fabadeczacilik.1134520 |
| MLA | Gozelle Mahmut,Kılıç Süloğlu Aysun Synthesis of 2-Substitutedbenzimidazolium Tetrachloroplatinate(II) Compounds and Their Cytotoxic Activities on Different Cell Lines. FABAD Journal of Pharmaceutical Sciences, vol.47, no.3, 2022, ss.281 - 292. 10.55262/fabadeczacilik.1134520 |
| AMA | Gozelle M,Kılıç Süloğlu A Synthesis of 2-Substitutedbenzimidazolium Tetrachloroplatinate(II) Compounds and Their Cytotoxic Activities on Different Cell Lines. FABAD Journal of Pharmaceutical Sciences. 2022; 47(3): 281 - 292. 10.55262/fabadeczacilik.1134520 |
| Vancouver | Gozelle M,Kılıç Süloğlu A Synthesis of 2-Substitutedbenzimidazolium Tetrachloroplatinate(II) Compounds and Their Cytotoxic Activities on Different Cell Lines. FABAD Journal of Pharmaceutical Sciences. 2022; 47(3): 281 - 292. 10.55262/fabadeczacilik.1134520 |
| IEEE | Gozelle M,Kılıç Süloğlu A "Synthesis of 2-Substitutedbenzimidazolium Tetrachloroplatinate(II) Compounds and Their Cytotoxic Activities on Different Cell Lines." FABAD Journal of Pharmaceutical Sciences, 47, ss.281 - 292, 2022. 10.55262/fabadeczacilik.1134520 |
| ISNAD | Gozelle, Mahmut - Kılıç Süloğlu, Aysun. "Synthesis of 2-Substitutedbenzimidazolium Tetrachloroplatinate(II) Compounds and Their Cytotoxic Activities on Different Cell Lines". FABAD Journal of Pharmaceutical Sciences 47/3 (2022), 281-292. https://doi.org/10.55262/fabadeczacilik.1134520 |
