SÜBSTİTÜE BENZİMİDAZOL LİGANDLARI TAŞIYAN BAZI YENİ PLATİN (II) KOMPLEKSLERİNİN SENTEZİ VE ANTİKANSER AKTİVİTESİ
Yıl 2026,
Cilt: 27 Sayı: 2
,
163
-
167
,
16.04.2026
Mevlüt Akdağ
,
Meral Sarper
,
Azime Berna Özçelik
,
Semra Utku
Öz
AMAÇ: Platin bazlı bileşikler, çeşitli kanser türlerinin tedavisinde önemli terapötik ilaçlar olarak rol alırlar. Sisplatinin (cis-[Pt(NH3)2Cl2]) tedaviye sunulması platini ve diğer metalleri baz alan bileşiklerin kanser tedavisinde potansiyel tedaviler olarak kullanılmasında önemli bir gelişme olmuştur. Karboplatin ve oksaliplatin dünya çapında biliniyorken birkaç ilaç sadece belli bölgelerde onay almıştır. Yeni antikanser terapilerin geliştirilmesine acil ihtiyaç vardır çünkü mevcut ilaçların toksisitesi çok yüksektir ve bu da kullanımlarını kısıtlayan en önemli faktörlerden biridir. Bu çalışma antikanser aktiviteye sahip yeni platin kompleksleri bulmayı hedeflemektedir.
GEREÇ VE YÖNTEM: Yeni platin türevlerinin geliştirilmesine yönelik bir strateji ayrılmayan grupların modifikasyonudur. Bu çalışmada 2-(2 or 4- triflorometil)fenil benzimidazol taşıyıcı ligandlarını içeren platin (II) kompleksleri sentezlenmiş ve MCF-7 hücrelerine karşı değerlendirilmiştir.
BULGULAR: Sonuçlarımız kompleks 1 ve 2’nin MCF-7 hücrelerine karşı sırasıyla 141.57 μM ve 125.59 μM IC50 değeriyle inhibitör aktivite gösterdiğini ortaya koymuştur.
SONUÇ: Bu kompleksler ileriki çalışmalar için lider bileşikler olarak değerlendirilebilir. Çeşitli modifikasyonlarla oluşturulan yeni serilerden in vitro aktivitesi daha yüksek ajanlar geliştirilebilir.
Kaynakça
-
1. Akdağ M, Özçelik Ab. Geniş Spektrumlu Antikanser Bileşikler Geliştirmeye Yönelik Potansiyel Bir Hedef: Heksokinaz-II. Journal Of Faculty Of Pharmacy Of Ankara University. 2022;46(1):182-92.
-
2. Berger MF, Lawrence MS, Demichelis F, et al. The Genomic Complexity Of Primary Human Prostate Cancer.
Nature. 2011;470(7333):214-20.
-
3. Ikushima H, Miyazono K. Tgfβ Signalling: A Complex Web In Cancer Progression. Nat. Rev. Cancer.
2010;10(6):415-24.
-
4. Alkaç İM, Keskin S, Çerçi B. Nanotaşıyıcıların Kanser Hücrelerine Aktif ve Pasif Olarak Hedeflenmesinde
Kullanılan yöntemler. Kocatepe Tıp Dergisi. 2024;25(3):396-406.
-
5. Czarnomysy R, Radomska D, Szewczyk OK, et al. Platinum And Palladium Complexes As Promising Sources For
Antitumor Treatments. International Journal Of Molecular Sciences. 2021;22(15):8271.
-
6. Ho GY, Woodward N, Coward JI. Cisplatin Versus Carboplatin: Comparative Review Of Therapeutic
Management In Solid Malignancies. Critical Reviews In Oncology/Hematology. 2016;102:37-46.
-
7. Kabasakal G, Tural E, Ünal MS. Deneysel Overyan Yetmezliklerde Mezenkimal Kök Hücrelerin Ovaryum
Dokusuna Etkisi. Kocatepe Tıp Dergisi. 2023;24(2):249-53.
-
8. Galanski M, Jakupec MA, Keppler BK. Update Of The Preclinical Situation Of Anticancer Platinum Complexes:
Novel Design Strategies And Innovative Analytical Approaches. Current Medicinal Chemistry. 2005;12(18):2075-
94.
-
9. Zhu H, Luo H, Zhang W, et al. X. Molecular Mechanisms Of Cisplatin Resistance In Cervical Cancer. Drug
Design, Development And Therapy. 2016:1885-95.
-
10. Liu W, Gust R. Update On Metal N-Heterocyclic Carbene Complexes As Potential Anti-Tumor Metallodrugs.
Coordination Chemistry Reviews. 2016;329:191-213.
-
Compounds IC50 values (μM) Complex 1 141.57 Complex 2 125.59 Cis-platin 40.84
-
11. Afzal M, Alarifi A, Abduh NA, et al. Identification Of Anti-Cancer Organometallic Compounds By Inhibition Of
BCL-2/Bax Interactions. Computers In Biology And Medicine. 2023;167:107657.
-
12. Almeida CM, S. Marcon PH, Nascimento ÉC, et al. Organometallic Gold (III) And Platinum (II) Complexes With
Thiosemicarbazone: Structural Behavior, Anticancer Activity, And Molecular Docking. Applied Organometallic Chemistry. 2022;36(8):E6761.
-
13. Özçelik AB, Utku S, Gümüş F, et al. Cytotoxicity And DNA Interactions of Some Platinum (II) Complexes With
Substituted Benzimidazole Ligands. Journal Of Enzyme Inhibition And Medicinal Chemistry. 2012;27(3):413-8.
-
14. Oun R, Moussa YE, Wheate NJ. The Side Effects Of Platinum-Based Chemotherapy Drugs: A Review For
Chemists. Dalton Transactions. 2018;47(19):6645-53.
-
15. Kopacz-Bednarska A, Król T. Selected Platinum Complexes In Standard And Modern Anti-Cancer Therapies.
Biuletyn Polskiego Towarzystwa Onkologicznego Nowotwory. 2022;7(2):106-15.
-
16. Alassadi S, Pisani MJ, Wheate NJ. A Chemical Perspective On The Clinical Use Of Platinum-Based Anticancer
Drugs. Dalton Transactions. 2022;51(29):10835-46.
-
17. Yu C, Wang Z, Sun Z, et al. Platinum-Based Combination Therapy: Molecular Rationale, Current Clinical Uses,
And Future Perspectives. Journal Of Medicinal Chemistry. 2020;63(22):13397-412.
-
18. Ghosh S. Cisplatin: The First Metal Based Anticancer Drug. Bioorganic Chemistry. 2019;88:102925.
-
19. Curini R, Materazzi S, D'Ascenzo G, et al. Thermal Behaviour Of Biologically Interesting Coordination
Compounds Of Benzimidazole With Divalent Metal Ions. Thermochimica Acta. 1990;161(2):297-307.
-
20. Özçelik AB, Gümüş F, Süloğlu Ak, et al. Cytotoxic Activity Studies Of Some Platinum (II) Complexes With 2-
Substitutedbenzimidazole Ligands. Revue Roumaine De Chimie. 2019;64(9):829-34.
-
21. Özçelik AB, Gümüş F, Sağkan RI, Muşabak U. Synthesis Of Platinum (II) Complexes Of 2-Cycloalkyl-Substituted
Benzimidazoles And Their Cytotoxic Effects. Zeitschrift Für Naturforschung C. 2015;70(9-10):243-50.
-
22. Utku S, Özçelik AB, Gümüş F, et al. Synthesis, In-Vitro Cytotoxic Activity And DNA Interactions Of New
Dicarboxylatoplatinum (II) Complexes With 2-Hydroxymethylbenzimidazole As Carrier Ligands. Journal Of
Pharmacy And Pharmacology. 2014;66(11):1593-605.
-
23. Aljendy Y, Demirbağ HO, Bayram G, Utku S. 2, 5 (6)-Disübstitüebenzimidazol Türevi Ligandları Taşıyan Platin
Komplekslerinin Antikanser Aktivitelerinin Araştırılması. Journal of Faculty of Pharmacy of Ankara University.
2023;47(2):531-42.
-
24. Doğan U, Özcan Ö, Alaca G, et al. Novel Benzimidazole-Platinum (II) Complexes: Synthesis, Characterization,
Antimicrobial And Anticancer Activity. Journal Of Molecular Structure. 2021;1229:129785.
-
25. Nagasawa Y, Matsusaki Y, Hotta T, et al. Aerobic Photooxidative Synthesis Of Benzimidazoles From Aromatic
Aldehydes And Diamines Using Catalytic Amounts Of Magnesium Iodide. Tetrahedron Letters.
2014;55(48):6543-6.
-
26. Huynh T-K-C, Nguyen T-H-A, Tran N-H-S, Nguyen T-D, Hoang T-K-D. A Facile And Efficient Synthesis Of
Benzimidazole As Potential Anticancer Agents. Journal Of Chemical Sciences. 2020;132:1-9.
-
27. Lippert B. Platinum Nucleobase Chemistry. Progress In Inorganic Chemistry. 2009;37:1-97
SYNTHESIS AND ANTICANCER ACTIVITY OF SOME NEW PLATINUM (II) COMPLEXES BEARING SUBSTITUTED BENZIMIDAZOLE LIGANDS
Yıl 2026,
Cilt: 27 Sayı: 2
,
163
-
167
,
16.04.2026
Mevlüt Akdağ
,
Meral Sarper
,
Azime Berna Özçelik
,
Semra Utku
Öz
OBJECTIVE: Platinum-based compounds serve as crucial therapeutic remedies for treating various types of cancer. The introduction of cisplatin, or cis-[Pt(NH3)2Cl2], marked a significant breakthrough in harnessing platinum and other metal-based compounds as potential treatments for cancer. While carboplatin and oxaliplatin have secured global recognition, a few drugs have obtained approval in only specific regions. There is an urgent need of new anticancer therapies, since the available drugs are so toxic which is one of the main reasons restricting the application of these drugs. This study aims to find new platinum complexes endowed with anticancer activity.
MATERIAL AND METHODS: One strategy to develop novel platinum derivatives involves modifying the non-leaving groups. In this research, platinum (II) complexes bearing 2-(2 or 4-trifloromethyl)phenyl benzimidazole carrier ligands were synthesized and evaluated against MCF-7 cells.
RESULTS: Our results showed that complex 1 and 2 showed inhibitory activity against MCF-7 cells with IC50 values 141.57 μM and 125.59 μM respectively.
CONCLUSIONS: These complexes can be evaluated as lead compounds for further studies. New series created with various modifications may yield agents with higher in vitro activity.
Kaynakça
-
1. Akdağ M, Özçelik Ab. Geniş Spektrumlu Antikanser Bileşikler Geliştirmeye Yönelik Potansiyel Bir Hedef: Heksokinaz-II. Journal Of Faculty Of Pharmacy Of Ankara University. 2022;46(1):182-92.
-
2. Berger MF, Lawrence MS, Demichelis F, et al. The Genomic Complexity Of Primary Human Prostate Cancer.
Nature. 2011;470(7333):214-20.
-
3. Ikushima H, Miyazono K. Tgfβ Signalling: A Complex Web In Cancer Progression. Nat. Rev. Cancer.
2010;10(6):415-24.
-
4. Alkaç İM, Keskin S, Çerçi B. Nanotaşıyıcıların Kanser Hücrelerine Aktif ve Pasif Olarak Hedeflenmesinde
Kullanılan yöntemler. Kocatepe Tıp Dergisi. 2024;25(3):396-406.
-
5. Czarnomysy R, Radomska D, Szewczyk OK, et al. Platinum And Palladium Complexes As Promising Sources For
Antitumor Treatments. International Journal Of Molecular Sciences. 2021;22(15):8271.
-
6. Ho GY, Woodward N, Coward JI. Cisplatin Versus Carboplatin: Comparative Review Of Therapeutic
Management In Solid Malignancies. Critical Reviews In Oncology/Hematology. 2016;102:37-46.
-
7. Kabasakal G, Tural E, Ünal MS. Deneysel Overyan Yetmezliklerde Mezenkimal Kök Hücrelerin Ovaryum
Dokusuna Etkisi. Kocatepe Tıp Dergisi. 2023;24(2):249-53.
-
8. Galanski M, Jakupec MA, Keppler BK. Update Of The Preclinical Situation Of Anticancer Platinum Complexes:
Novel Design Strategies And Innovative Analytical Approaches. Current Medicinal Chemistry. 2005;12(18):2075-
94.
-
9. Zhu H, Luo H, Zhang W, et al. X. Molecular Mechanisms Of Cisplatin Resistance In Cervical Cancer. Drug
Design, Development And Therapy. 2016:1885-95.
-
10. Liu W, Gust R. Update On Metal N-Heterocyclic Carbene Complexes As Potential Anti-Tumor Metallodrugs.
Coordination Chemistry Reviews. 2016;329:191-213.
-
Compounds IC50 values (μM) Complex 1 141.57 Complex 2 125.59 Cis-platin 40.84
-
11. Afzal M, Alarifi A, Abduh NA, et al. Identification Of Anti-Cancer Organometallic Compounds By Inhibition Of
BCL-2/Bax Interactions. Computers In Biology And Medicine. 2023;167:107657.
-
12. Almeida CM, S. Marcon PH, Nascimento ÉC, et al. Organometallic Gold (III) And Platinum (II) Complexes With
Thiosemicarbazone: Structural Behavior, Anticancer Activity, And Molecular Docking. Applied Organometallic Chemistry. 2022;36(8):E6761.
-
13. Özçelik AB, Utku S, Gümüş F, et al. Cytotoxicity And DNA Interactions of Some Platinum (II) Complexes With
Substituted Benzimidazole Ligands. Journal Of Enzyme Inhibition And Medicinal Chemistry. 2012;27(3):413-8.
-
14. Oun R, Moussa YE, Wheate NJ. The Side Effects Of Platinum-Based Chemotherapy Drugs: A Review For
Chemists. Dalton Transactions. 2018;47(19):6645-53.
-
15. Kopacz-Bednarska A, Król T. Selected Platinum Complexes In Standard And Modern Anti-Cancer Therapies.
Biuletyn Polskiego Towarzystwa Onkologicznego Nowotwory. 2022;7(2):106-15.
-
16. Alassadi S, Pisani MJ, Wheate NJ. A Chemical Perspective On The Clinical Use Of Platinum-Based Anticancer
Drugs. Dalton Transactions. 2022;51(29):10835-46.
-
17. Yu C, Wang Z, Sun Z, et al. Platinum-Based Combination Therapy: Molecular Rationale, Current Clinical Uses,
And Future Perspectives. Journal Of Medicinal Chemistry. 2020;63(22):13397-412.
-
18. Ghosh S. Cisplatin: The First Metal Based Anticancer Drug. Bioorganic Chemistry. 2019;88:102925.
-
19. Curini R, Materazzi S, D'Ascenzo G, et al. Thermal Behaviour Of Biologically Interesting Coordination
Compounds Of Benzimidazole With Divalent Metal Ions. Thermochimica Acta. 1990;161(2):297-307.
-
20. Özçelik AB, Gümüş F, Süloğlu Ak, et al. Cytotoxic Activity Studies Of Some Platinum (II) Complexes With 2-
Substitutedbenzimidazole Ligands. Revue Roumaine De Chimie. 2019;64(9):829-34.
-
21. Özçelik AB, Gümüş F, Sağkan RI, Muşabak U. Synthesis Of Platinum (II) Complexes Of 2-Cycloalkyl-Substituted
Benzimidazoles And Their Cytotoxic Effects. Zeitschrift Für Naturforschung C. 2015;70(9-10):243-50.
-
22. Utku S, Özçelik AB, Gümüş F, et al. Synthesis, In-Vitro Cytotoxic Activity And DNA Interactions Of New
Dicarboxylatoplatinum (II) Complexes With 2-Hydroxymethylbenzimidazole As Carrier Ligands. Journal Of
Pharmacy And Pharmacology. 2014;66(11):1593-605.
-
23. Aljendy Y, Demirbağ HO, Bayram G, Utku S. 2, 5 (6)-Disübstitüebenzimidazol Türevi Ligandları Taşıyan Platin
Komplekslerinin Antikanser Aktivitelerinin Araştırılması. Journal of Faculty of Pharmacy of Ankara University.
2023;47(2):531-42.
-
24. Doğan U, Özcan Ö, Alaca G, et al. Novel Benzimidazole-Platinum (II) Complexes: Synthesis, Characterization,
Antimicrobial And Anticancer Activity. Journal Of Molecular Structure. 2021;1229:129785.
-
25. Nagasawa Y, Matsusaki Y, Hotta T, et al. Aerobic Photooxidative Synthesis Of Benzimidazoles From Aromatic
Aldehydes And Diamines Using Catalytic Amounts Of Magnesium Iodide. Tetrahedron Letters.
2014;55(48):6543-6.
-
26. Huynh T-K-C, Nguyen T-H-A, Tran N-H-S, Nguyen T-D, Hoang T-K-D. A Facile And Efficient Synthesis Of
Benzimidazole As Potential Anticancer Agents. Journal Of Chemical Sciences. 2020;132:1-9.
-
27. Lippert B. Platinum Nucleobase Chemistry. Progress In Inorganic Chemistry. 2009;37:1-97