IN SILICO TRIAL APPROACHES BETWEEN PHYTOCHEMICAL COMPOSITION OF VERBENA OFFICINALIS AND LIVER CANCER TARGETS

Year 2024, , 975 - 992, 10.09.2024

Hatice Akkaya , Aydın Özmaldar

https://doi.org/10.33483/jfpau.1417289

Abstract

Objective: The abundance of bioactive metabolites in Verbena officinalis explains the biological benefits and folkloric use of the plant. Liver cancer is an extremely heterogeneous malignant disease compared to other defined tumors. To explore the potential therapeutic value of bioactive metabolites in Verbena officinalis, this study aimed to filter secondary metabolites, conduct ADME-Tox assessments, perform drug similarity tests, and analyze with molecular dynamic simulations. The objective was to evaluate how potential drug candidates derived from Verbena officinalis behave in biological systems and assess their potential toxicity risks.
Material and Method: Ligands selected from the ADME assay were utilized in in silico molecular docking studies against Glucose-6-phosphate dehydrogenase enzyme in the oxidative part of the pentose phosphate pathway, which is crucial for liver diseases. These studies were conducted using Autodock Vina embedded in Chimera 1.16. Molecular dynamics simulations were performed with the AMBER16.
Result and Discussion: When the ADME test results were evaluated, 88 secondary metabolites were identified as ligands. Among all the ligands evaluated against Glucose-6-phosphate dehydrogenase enzyme, which is the key enzyme of the pentose phosphate pathway, quercetin flavonoid was determined to be the most active ligand with a docking score of -8.1 kcal/mol and binding energy of -118.51 kcal/mol. A molecular dynamics simulation performed for 300 nanoseconds confirmed that quercetin can remain stable in its microenvironment. The activity of this metabolite is worthy of further testing in vitro and in vivo as it may highlight a therapeutic modality within the pentose phosphate pathway.

Keywords

In silico, liver cancer, pentose phosphate pathway, toxicitiy, Verbena officinalis

VERBENA OFFICINALIS'İN FİTOKİMYASAL BİLEŞİMİ İLE KARACİĞER KANSERİ HEDEFLERİ ARASINDAKİ İN SİLİKO DENEME YAKLAŞIMLARI

Abstract

Amaç: Verbena officinalis bitkisinde bulunan biyoaktif metabolitlerin bolluğu, bitkinin biyolojik faydalarını ve halk arasındaki kullanımını açıklar. Karaciğer kanseri, diğer tanımlanmış tümörlere kıyasla son derece heterojen kötü huylu bir hastalıktır. Verbena officinalis'teki biyoaktif metabolitlerin potansiyel terapötik değerini keşfetmek için, bu çalışma ikincil metabolitleri filtrelemeyi, ADME-Tox değerlendirmeleri yapmayı, ilaç benzerlik testleri gerçekleştirmeyi ve moleküler dinamik simülasyonları ile analiz etmeyi amaçlamıştır. Hedef, Verbena officinalis'ten elde edilen potansiyel ilaç adaylarının biyolojik sistemlerde nasıl davrandığını değerlendirmek, potansiyel toksisite risklerini değerlendirmekti.
Gereç ve Yöntem: ADME testinden seçilen ligandlar, karaciğer hastalıkları için önemli olan pentoz fosfat yolunun oksidatif kısmındaki Glukoz-6-fosfat dehidrogenaz enzimi için in siliko moleküler bağlanma çalışmalarında kullanıldı. Bu çalışmalar Chimera 1.16'ya gömülü Autodock Vina kullanılarak gerçekleştirildi. Moleküler dinamik simülasyonları AMBER16 programı ile gerçekleştirildi.
Sonuç ve Tartışma: ADME test sonuçları değerlendirildiğinde, 88 sekonder metabolit ligand olarak belirlendi. Pentoz fosfat yolunun anahtar enzimi olan Glukoz-6-fosfat dehidrogenaz enzimine karşı değerlendirilen tüm ligandlar arasında, kuersetin flavonoidi, -8.1 kcal/mol bağlanma skoru ve -118.51 kcal/mol bağlanma enerjisi ile en etkin ligand olarak belirlendi. 300 nanosaniye boyunca yapılan moleküler dinamik simülasyonu ise quercetinin bulunduğu mikroçevrede stabil olarak kalabildiğini doğruladı. Bu metabolitin aktivitesi, pentoz fosfat yolu içinde terapötik bir modaliteyi ortaya koyabileceği için in vitro ve in vivo testlerle daha ileri incelenmeye değerdir.

Keywords

İn siliko, karaciğer kanseri, pentoz fosfat yolu, toksisite, Verbena officinalis

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