TOPOİZOMERAZ İNHİBİTÖRLERİ OLARAK BAZI BENZAMİD TÜREVLERİ ÜZERİNDE MOLEKÜLER DOKİNG ÇALIŞMALARI

Öz

Amaç: Antikanser aktivite göstereceği düşünülen Bazı benzamid türevlerinin insan Topo I ve IIα enzimleri ile moleküler düzeydeki etkileşimlerinin incelenmesi amacıyla bu enzimler üzerinden doking çalışmaları gerçekleştirilmiştir.

Gereç ve Yöntem: Doking çalışmalarının gerçekleştirilmesinde protein veri bankasından Topo I için (1K4T) ve Topo IIα için (5GWK) seçilmiştir, Discovery studio 3.5 programı kullanılarak CDocker yöntemiyle doking işlemi yapılmış ve benzamid türevlerinin enzimlere bağlanma enerjileri hesaplanmış ve moleküler etkileşimleri ortaya çıkartılmıştır.

Sonuç ve Tartışma: Topo I ve IIα üzerinden yapılan docking işlemi sonucunda benzamid türevi bileşiklerin Topo IIα enzimine afinitesinin daha yüksek olduğu bulunmuştur. 4N6, 5N5 bileşikleri Topo I; 5N3, 5N7 bileşikleri de Topo IIα inhbitörleri olarak antikanser aktivite göstermesi açısından umut verici bileşikler olarak belirlenmiştir.

Anahtar Kelimeler

• Antikanser
• Benzamid
• Doking
• Topoizomeraz I
• Topoizomeraz IIα

MOLECULAR DOCKING STUDIES ON SOME BENZAMIDE DERIVATIVES AS TOPOISOMERASE INHIBITORS

Öz

Objective: In order to examine the interactions of some benzamide derivatives, which are thought to exhibit anti-cancer activity, with human Topo I and IIα enzymes at the molecular level, docking studies were carried out on these enzymes.

Material and Method: In conducting the docking studies, the protein was selected from the protein data bank for Topo I (1K4T) and for Topo IIα (5GWK). Doking was performed with the CDocker method using the Discovery studio 3.5 program, and the binding energies of benzamide derivatives to enzymes were calculated and their molecular interactions were revealed.

Result and Discussion: As a result of the docking process on Topo I and IIα, it was found that benzamide derivative compounds have higher affinity for Topo IIα enzyme. For Topo I compounds 4N6, 5N5; for Topo IIa compounds 5N3, 5N7 have been identified as promising compounds in terms of anticancer activity.

Anahtar Kelimeler

• Anticancer
• Benzamide
• Docking
• Topoisomerase I
• Topoisomerase IIα

Kaynakça

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