Yapı Aktivite İlişkisi (SAR): Bromlanmış 8-hidroksikinolin ve ftalonitril türevlerinin çeşitli kanser hücre hatları üzerine antiproliferatif aktivitelerinin incelenmesi

Year 2017, , 1300 - 1306, 01.12.2017

Salih Ökten , Tuğba Kul Köprülü , Osman Çakmak Şaban Tekin

https://doi.org/10.16984/saufenbilder.313873

Abstract

Bu çalışmada, 8-hidroksikinolin’den ftalonitriller 6, 7
ve bunların bromlu türevleri 8, 9 sentezlenerek bu moleküllerin C6
(sıçan glial tümör), HeLa (insan rahim ağzı kanser hücresi) ve HT29 (insan adenokarsinoma)
kanser hücre hatları üzerindeki antiproliferatif ve sitotoksik aktiviteleri
araştırılmıştır. 7-Bromo- ve 5,7-dibromo-8-hidroksikinolin türevleri (2 ve 3) ile ftalonitril 6, 7 ve bunların bromlu türevleri 8, 9
antiproliferatif ve apoptotik etkileri yapı aktivite ilişkisi (SAR) yönüyle
karşılaştırılmıştır. Bromohidroksikinolin 2
ve 3 türevleri, literatür
kayıtlarına göre yüksek antiproliferatif aktivite göstermesine rağmen,
8-hidroksikinolinden hazırlanan ftalonitril bileşikleri 6, 7 ve bromlanan 8, 9
türevlerinin antiproliferatif aktiviteyi belirgin bir biçimde azalttığı
belirlenmiştir. Kinolin çekirdeğinin C-8 konumundaki yapı aktivite çalışması,
antiproliferatif ve apoptotik aktivitenin OH grubunun sebep olduğu ortaya
çıkartmıştır. Ayrıca kinolin halkasının OH grubuna alkil ya da sübstitüe
halkalı grupların bağlanması ve bromlanması da antiproliferatif aktiviteyi
düşürmüştür.

Keywords

8-hidroksikinolin, ftalonitril, yapı-aktivite ilişkisi (SAR), antiproliferatif aktivite, apoptotik aktivite, antitopoizomeraz

Structure-Activity Relationship (SAR): The study of antiproliferative activities of brominated 8-hydroxyquinoline and phthalonitrile derivatives on several cancer cell lines

Abstract

In this study, phthalonitriles 6, 7 and their
corresponding bromo derivatives 8, 9 were synthesized from
8-hydroxyquinoline to investigate antiproliferative and cytotoxic activities on
C6 (rat brain tumor), HeLa (human cervix carcinoma) and HT29 (human colon
carcinoma) cancer cell lines of these molecules. The antiproliferative and
apoptotic effects of 7-bromo- and 5,7-dibromo-8-hydroxyquinoline derivatives (2 and 3) and phthalonitrile 6,
7 and their brominated derivatives 8, 9
were compared in terms of Structure Activity Relationship (SAR). Although
bromohydroxyquinoline derivatives 2
and 3 exhibited high
antiproliferative activity according to literature, it has been determined that
phthalonitrile compounds 6, 7 and their brominated 8, 9
derivatives are significantly reduced in antiproliferative activity. The SAR of
the quinoline core at C-8 revealed that OH group lead to antiproliferative and
apoptotic activity. In addition, biological activity was decreased when alkyl
or substituted cyclic groups bounded to OH of quinoline, and the bromination of
these derivatives did not increase the antiproliferative activity.

Keywords

8-hydroxyquinoline, phthalonitrile, structure-activity relationship (SAR), antiproliferative activity, apoptotic activity

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