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

Year 2017, Issue: 2, 143 - 156, 05.09.2017

Osman Çakmak , Salih Ökten , Şaban Tekin Tuğba Kul Köprülü

Abstract

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.   

Keywords

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)

Abstract

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.  

Keywords

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

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