EVALUATION OF ZERUMBONE AS AN EGFR TYROSINE KINASE INHIBITOR BY MOLECULAR DOCKING METHOD

Abstract

Objective: EGFR-TK domain is of great importance in the initiation and progression of various cancer types, especially lung cancer. The existing EGFR-TK inhibitors have numerous side effects, which make them improper to be utilized as cancer therapeutics. In this study, we aimed to analyze the activity of zerumbone as an anticancer agent targeting EGFR by molecular docking approach and to evaluate its activity in comparison with curcumin.

Material and Method: MEP and HOMO-LUMO analyses were achieved at B3LYP/6-31G(D,P) level to evaluate electrostatic interactions that affect binding of EGFR with zerumbone and curcumin. Their binding energies were determined by molecular docking and compared with erlotinib as reference ligand.

Result and Discussion: Docking studies showed higher bindings (lower binding energy) for curcumin and zerumbone with binding energies -8.0 and -7.6 kcal/mol, respectively, compared to erlotinib (-7.3 kcal/mol). However, there is no significant difference between them. The ΔE energy gap of zerumbone was 5.09 eV which implies that this compound has more stability in comparison with curcumin (ΔE=3.68 eV) and erlotinib (ΔE=4.29eV). Also, zerumbone showed strong hydrogen bond interactions with EGFR, making it candidate as EGFR inhibitor, as did both in curcumin and erlotinib. It was concluded that zerumbone may have potential for inhibitory activity against EGFR-TK.

Keywords

• Curcumin
• epidermal growth factor receptor
• lung cancer
• molecular docking
• zerumbone

MOLEKÜLER YERLEŞTİRME YÖNTEMİYLE ZERUMBONUN EGFR TİROZİN KİNAZ İNHİBİTÖRÜ OLARAK DEĞERLENDİRİLMESİ

Abstract

Amaç: EGFR-TK bölgesi, başta akciğer kanseri olmak üzere çeşitli kanser türlerinin başlaması ve ilerlemesinde büyük önem taşımaktadır. Mevcut EGFR-TK inhibitörlerinin çeşitli yan etkilerinin varlığı, onların uygun kanser terapötikleri olarak kullanılmalarını sınırlandırmaktadır. Bu çalışmada, moleküler yerleştirme yaklaşımı ile EGFR'yi hedef alan bir antikanser ajan olarak zerumbonun aktivitesini analiz etmeyi ve aktivitesini kurkumin ile karşılaştırmalı olarak değerlendirmeyi amaçladık.

Gereç ve Yöntem: EGFR'nin zerumbon ve kurkumin ile bağlanmasını etkileyen elektrostatik etkileşimleri değerlendirmek için B3LYP/6-31G(D,P) seviyesinde MEP ve HOMO-LUMO analizleri yapıldı. Bağlanma enerjileri moleküler yerleştirme ile belirlendi ve referans ligand olarak erlotinib ile karşılaştırıldı.

Sonuç ve Tartışma: Yerleştirme çalışmaları, erlotinib (-7.3 kcal/mol) ile karşılaştırıldığında, sırasıyla -8.0 ve -7.6 kcal/mol bağlanma enerjileriyle kurkumin ve zerumbon için daha yüksek bağlanmalar (düşük bağlanma enerjisi) gösterdi. Ancak aralarında önemli bir fark gözlenmedi. Zerumbonun ΔE enerji aralığı 5.09 eV olarak bulundu. Bu sonuç, bu bileşiğin kurkumin (ΔE=3.68 eV) ve erlotinib ile karşılaştırıldığında (ΔE=4.29 eV) daha fazla kararlılığa sahip olduğu anlamına gelmektedir. Ayrıca, zerumbon EGFR ile güçlü hidrojen bağı etkileşimleri gösterdi ve bu da onun hem kurkumin hem de erlotinib'deki gibi EGFR inhibitörü olarak potansiyeli olduğunu göstermiştir. Zerumbonun EGFR-TK'ye karşı inhibitör aktiviteye sahip olabileceği sonucuna varıldı.

Keywords

• Akciğer kanseri
• epidermal büyüme faktörü reseptörü
• kurkumin
• moleküler yerleştirme
• zerumbon

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