Bromlanmış 8-Hidroksi Kinolinlerin ve Palladyum Komplekslerinin Antikanser Özelliklerinin İncelenmesi: Yapı-Aktivite İlişkisi (SAR)

Öz

Amaç: Bu çalışmada, 7-bromo-8-hidroksikinolin (2) ve 5,7-dibrom-8-hidroksikinolin (3) bileşiklerinin Palladyum (Pd) kompleksleri sentezlendi. Oluşan kompleks bileşikler (4 ve 5) ile başlangıç bileşiklerinin (2 ve 3) antikanser potansiyelleri ve sitotoksisiteleri karşılaştırmalı olarak incelendi.

Yöntem: 8-Hidroksikinolin (8-OHQ, 1), moleküler brom (Br₂) ile  muamele edildi. Reaksiyon sonucu, 7-bromo-8-hidroksikinolin (7-Br-8-OHQ, 2) ve 5,7-dibromo-8-hidroksikinolin (5,7-diBr-8-OHQ, 3) elde edildi. Bu moleküller, kompleksleşme reaksiyonları ile Palladyum koordinasyon bileşiklerine (4 ve 5) dönüştürüldü. Sentezlenen bileşik ve komplekslerin (2 -5) antikanser potansiyel ve özellikleri incelendi. Bu amaçla HeLa, HT29 ve C6 hücre hatlarına karşı SRB hücre proliferasyonu ile LDH sitotoksisite testleri uygulandı.

Bulgular: 7-Br-8-OHQ 2 ve 5,7-dibromo-8-OHQ 3 bileşikleri test edilen hücre hatlarının hücre proliferasyonunu inhibe etmiştir.  Fakat bu bileşiklerin Palladyum (Pd) kompleksleri (4 ve 5) durumunda antiproliferatif etki önemli derecede azalmıştır. 7-Br-8-OHQ 2 ve 5,7-diBr-8-OHQ 3  bileşikleri HeLa hücre hatlarında düşük sitotoksik etki göstermesine rağmen, bu bileşiklerin (2 ve 3) C6 hücre hatlarında oldukça sitotoksik olduğu belirlenmiştir.

Sonuç: Kinolin halkasında  C-8 konumunda –OH (hidroksi) fonksiyonel grubu yanında brom gruplarının bağlı olması   yüksek antiproliferatif etkiden sorumlu olduğu düşünülmektedir. Kompleksleşme ile kinolin yapısındaki hidroksi ve amin grupları bloke edilmektedir. Bu yüzden kompleks bileşikler (4 ve 5) durumunda  antikanser aktivite oldukça azalmaktadır.   

Anahtar Kelimeler

• Pd koordinasyon kompleksi,antikanser,sitotoksik aktivite,Bromo-8-hidroksikinolin,şelat,yapı-aktivite ilişkisi

The Studies of Anti-Cancer Activity of Brominated 8-Hydroxy Quinolines and Their Palladium Complexes: Structure-Activity Relationship (SAR)

Öz

Aim: In this study, Pd coordination complexes of 7-bromo-8-hydroxyquinoline (7-Br-8-OHQ, 2) and 5,7-dibromo-8-hydroxyquinoline (5,7-diBr-8-OHQ,3) were prepared. The anticancer and cytotoxic potentials of Palladium complexes (4 and 5) obtained from bromo hydroxides 2 and 3 were studied comparatively.

Method: 7-bromo-8-hydroxyquinoline (7-Br-8OHQ, 2) and 5,7-dibromo-8-hydroxyquinoline (5,7-diBr-8-OHQ,3) were generated when 8-hydroxyquinoline (1) was treated with molecular bromine (Br₂). These compounds were converted to corresponding Pd coordination compounds 4 and 5 via complexation reactions. Antiproliferative and Cytotoxic potentials of the compounds 2-5 against HeLa, HT29 and C6 cell lines were tested by using SRB cell proliferation and LDH cytotoxcity assays. 

Findings: 7-Br-8-OHQ 2 and 5,7-diBr-8-OHQ 3  inhibited the proliferation of all cell lines tested. The antiproliferative potential of Pd complexes (4 and 5) of the molecules (2 and 3) was significantly higher. The cytotoxic activities of 7-Br-8-OHQ 2 and 5,7-diBr-8-OHQ 3 were different on HeLa and C6 cells, indicating cell selective activity. 

Conclusion: We concluded that the OH functional group at C-8 position and the bromo groups at C5 and/or C7 positions of quinoline skeleton may be responsible for high antiproliferative potential. On the other hand, low anticancer activity of the coordination compounds (4 and 5) may be attributed to blocking hydroxy and amine groups of quinoline core by complexation.  

Anahtar Kelimeler

• Pd coordination complex,chelate,anticancer,cytotoxic activity,Bromo-8- hydroxyquinoline,structure-activity relationship (SAR)

Kaynakça

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