ANTİKANSER İLAÇLARIN HEDEF BAZLI TASARIMINDA FARKLI MEKANİZMALARLA ETKİLİ İNDOL TÜREVLERİ

Year 2019, , 334 - 358, 08.09.2019

Elif Ayça Dedeoğlu Meriç Köksal

https://doi.org/10.33483/jfpau.554118

Abstract

        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.

Keywords

antikanser, ilaç tasarım, indol

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

Abstract

        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.

Keywords

anticancer, drug design, indole

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