IN VITRO AND IN SILICO STUDIES ON LIGNAN SECOISOLARICIRESINOL DIGLUCOSIDE

Öz

Objective: Lignans are important biologically active compounds in diphenolic structure. Secoisolariciresinol diglucoside (SDG) is a significant type of lignan known to have anti-cancer properties. This study aimed to investigate the antiproliferative activity properties of SDG on hepatocellular carcinoma cells (HepG2), colorectal cancer cells (DLD-1), lung carcinoma (A549), and prostate cancer (PC3) cell lines. Material and Method: Cell viability of cancer cells was determined by the MTT method after treatment with various concentrations of SDG at 48 or 72 hours. The DFT (Density Functional Theory) analysis of the SDG was performed using Spartan'10 and visualized. Drug-likeness and absorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) properties of this compound were examined. Molecular docking was carried out to research the biological activity of SDG. Result and Discussion: Our results showed that SDG exhibited significant cytotoxicity only against DLD-1 cells with IC50 value of 37.45 µM, but inactive against other cancer cell lines as in vitro. 4UYA, which biomarker for colon cancer, is the crystal structure of the MLK4 kinase domain. The binding energy value for the SDG-MLK4 kinase domain was calculated as -6.1 kcal/mol. Anticancer potential was verified by in vitro assay and in silico molecular docking study. In conclusion, this study revealed the protective aspect of SDG against colon cancer and showed that it has promising anticancer activity.

Anahtar Kelimeler

• Cancer
• cytotoxicity
• DFT
• molecular docking
• SDG

LİGNAN SEKOİZOLARİSİRESİNOL DİGLUKOSİT ÜZERİNE İN VİTRO VE İN SİLİKO ÇALIŞMALAR

Öz

Amaç: Lignanlar, difenolik yapıda biyolojik olarak aktif önemli bileşiklerdir. Sekoizolarisiresinol diglukosit. (SDG), kanser önleyici özelliklere sahip olduğu bilinen önemli bir lignan türüdür. Bu çalışmada SDG'nin hepatoselüler karsinom hücreleri (HepG2), kolorektal kanser hücreleri (DLD-1), akciğer karsinomu (A549) ve prostat kanseri (PC3) hücre hatları üzerindeki antiproliferatif aktivite özelliklerinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Kanser hücrelerinin hücre canlılığı, 48 veya 72 saatte çeşitli SDG konsantrasyonları ile muamele edildikten sonra MTT yöntemiyle belirlendi. SDG’nin DFT (Yoğunluk Fonksiyonel Teorisi) analizi Spartan'10 kullanılarak yapıldı ve görselleştirildi. Bu bileşiğin ilaca benzerliği ve emilim, dağılım, metabolizma, atılım ve toksisite (ADME-Tox) özellikleri incelendi. SDG'nin biyolojik aktivitesini araştırmak için moleküler yerleştirme gerçekleştirildi. Sonuç ve Tartışma: Sonuçlarımız SDG'nin yalnızca IC50 değeri 37,45 µM olan DLD-1 hücrelerine karşı anlamlı sitotoksisite sergilediğini, diğer kanser hücre hatlarına karşı ise in vitro olarak inaktif olduğunu gösterdi. Kolon kanseri biyobelirteci olan 4UYA, MLK4 kinaz bölgesinin kristal yapısıdır. SDG-MLK4 kinaz alanına ait bağlanma enerjisi değeri -6,1 kcal/mol olarak hesaplandı. Antikanser potansiyeli in vitro analiz ve in silico moleküler yerleştirme çalışmasıyla doğrulandı. Sonuç olarak bu çalışma SDG’nin kolon kanserine karşı koruyucu yönünü ortaya koyarak umut verici antikanser etkinliğe sahip olduğunu göstermiştir.

Anahtar Kelimeler

• DFT
• kanser
• moleküler yerleştirme
• SDG
• sitotoksisite

Kaynakça

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