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Journals / Ankara Üniversitesi Eczacılık Fakültesi Dergisi / 2026 / Cilt: 50 Sayı: 2

INVESTIGATION OF THE INHIBITION MECHANISM OF SOME HDAC8 INHIBITORS THROUGH COMPUTATIONAL METHODS

BAZI HDAC8 İNHİBİTÖRLERİNİN İNHİBİSYON MEKANİZMASININ HESAPLAMALI YÖNTEMLERLE ARAŞTIRILMASI

Muhammed Tilahun Muhammed(Suleyman Demirel University)0000-0003-0050-5271
İrem Sarı(Süleyman Demirel University)0009-0001-1545-9725
Sude Nur Şahan(Süleyman Demirel University)0009-0007-0468-4955
Pages
289–300
Publication Date
2026-05-19
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

The MD simulation study disclosed that HDAC8-inhibitor complexes procured from the docking were stable during the 200 ns simulation.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Objective: Cancer remains one of the leading causes of death around the globe.
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Key Findings & Data:Therefore, there is a growing need for novel therapeutic strategies that are more effective with lower toxicity.
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Conclusion & Impact:The MD simulation study disclosed that HDAC8-inhibitor complexes procured from the docking were stable during the 200 ns simulation.
🔬Design:Araştırma Makalesi
📍Scope:2024 Verileri
⚙️Variables:HDAC8 · kanser · LibDock

Abstract

Objective: Cancer remains one of the leading causes of death around the globe. Current treatment methods are known for their side effects and resistance development. Therefore, there is a growing need for novel therapeutic strategies that are more effective with lower toxicity. Histone deacetylase 8 (HDAC8) overexpression has been linked to poor prognosis in cancer. Hence, HDAC8 is an attractive target in developing new anticancer agents. The objective of this study has been to elucidate mechanisms of action for some selected HDAC8 inhibitors through computational methods. Material and Method: In this study, binding modes of selected HDAC8 inhibitors to the enzyme structure were explored through docking via LibDock and molecular dynamics (MD) simulation via GROMACS 2024. Result and Discussion: The docking study disclosed that compound d exhibited the highest binding potential to the HDAC8 structure. The roles of hydroxamic acid, amide group, and aromatic rings in the HDAC8 inhibition were affirmed by the docking study. His180 and Tyr306 residues were found to be critical residues in the binding. The MD simulation study disclosed that HDAC8-inhibitor complexes procured from the docking were stable during the 200 ns simulation.

Özet

Amaç: Kanser dünya çapında önde gelen ölüm nedenlerinden biri olmaya devam etmektedir. Günümüzde uygulanan tedavi yöntemlerinin yan etkileri ve direnç geliştirmeleri bilinmektedir. Bu nedenle daha etkili ve düşük toksisiteye sahip yeni tedavi stratejilerine olan ihtiyaç artmaktadır. Histon deasetilaz 8 (HDAC8) aşırı ekspresyonunun kanserlerde kötü prognozla bağlantılı olduğu görülmüştür. Bu nedenle HDAC8 yeni kanser önleyici ajanların geliştirilmesinde cazip bir hedeftir. Bu çalışmanın amacı, bazı seçilmiş HDAC8 inhibitörlerinin etki mekanizmalarını hesaplamalı yöntemlerle açıklamaktır. Gereç ve Yöntem: Bu çalışmada, seçilmiş HDAC8 inhibitörlerinin enzim yapısına bağlanma şekilleri LibDock aracılığıyla doking ve GROMACS 2024 aracılığıyla moleküler dinamik (MD) simülasyon yaparak araştırılmıştır. Sonuç ve Tartışma: Yapılan doking çalışması bileşik d 'nin HDAC8 yapısına en yüksek bağlanma potansiyeli gösterdiğini ortaya koymuştur. HDAC8 inhibisyonunda hidroksamik asidin, amid grubun ve aromatik halkaların rolleri doking çalışmasıyla teyit edilmiştir. His180 ve Tyr306 kalıntılarının bağlanmada kritik kalıntılar oldukları bulunmuştur. MD simülasyon çalışması doking ile elde edilen HDAC8-inhibitör komplekslerin 200 ns simülasyon sırasında kararlı olduğunu ortaya koymuştur.

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Cite This Article

Muhammed, M. T., Sarı, İ., Şahan, S. N. (2026). INVESTIGATION OF THE INHIBITION MECHANISM OF SOME HDAC8 INHIBITORS THROUGH COMPUTATIONAL METHODS. Ankara Üniversitesi Eczacılık Fakültesi Dergisi, Cilt: 50 Sayı: 2, 289–300. https://doi.org/10.33483/jfpau.1751507

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