ANTİKANSER İLAÇLARIN HEDEF BAZLI TASARIMINDA FARKLI MEKANİZMALARLA ETKİLİ İNDOL TÜREVLERİ

Öz

        Amaç: Bu derlemenin amacı tübülin polimeraz, histon deasetilaz (HDAC), sirtuin (SIRT), PIM kinaz, DNA topoizomeraz ve sigma reseptörleri gibi farklı mekanizmalarla antikanser etkinlik gösteren doğal ve sentetik indol türevlerinin incelenmesi ve yapı-etki ilişkileri ışığında farklı etki yolakları bağlantısının irdelenmesidir.

        Sonuç ve Tartışma: İndol çekirdeği, birçok reseptöre ligant olarak uygunluğu ve yüksek reseptör affinitesi sebebiyle antikanser özelliği olan ve klinikte kullanılan birçok ilaç molekülünün iskeletini oluşturmaktadır. Bitkisel ya da marin kaynaklı elde edilen doğal indoller üzerinde doğru modifikasyonlar veya hibrit indollerin tasarlanması ile kanser hücreleri üzerinde seçici biyolojik hedeflere sahip öncü moleküllerin geliştirilmesi mümkün olmuştur. Seçici biyolojik hedeflere sahip antikanser ilaç geliştirilmesine yönelik araştırmalar ile kanser terapilerindeki yüksek yan etki, düşük etkinlik ve ilaç direnci gibi problemler çözülebilecektir.

Anahtar Kelimeler

• antikanser,ilaç tasarım,indol

A REVIEW ON INDOLE DERIVATIVES WITH DIVERSE MECHANISM IN THE TARGET-BASED DESIGN OF ANTICANCER DRUGS

Öz

        Objective: The review article aims to evaluate natural and synthetic indole derivatives that can act via diverse targets like tubulin polymerase, histone deacetylases (HDACs), sirtuins, PIM kinases, DNA topoisomerases and sigma receptors and to examine SAR studies in literature, coordinated by their biological targets.

        Result and Discussion: Due to conformity of versatile receptors as a ligand and high receptor affinity, indole has been formed the skeleton of clinically used anticancer molecules. The structural modification of natural compounds derived from plants or marine flora and generation of hybrid indoles make the development of lead compounds, which specifically target to the biological components possible. The studies about development of tumor-specific targeting of anticancer drug may overcome the problems of anticancer therapy like side effect, low potency and drug resistance.

Anahtar Kelimeler

• anticancer,drug design,indole

Kaynakça

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