Gentiana Dinarica'dan Türetilen Fitokimyasalların Kolorektal Kanser için Potansiyel İlaç Adayları Olarak Hesaplamalı Yaklaşımlarla İncelenmesi

Abstract

Kolorektal kanser, dünya çapında en ölümcül kanserlerden biridir ve en umut verici sonuçlar için erken müdahale gerektirir. Mevcut tedaviler arasında, metastaz riskini azaltmada etkili olmalarına rağmen, genellikle sağlıklı hücrelere zarar veren ve olumsuz yan etkiler nedeniyle hastada önemli sıkıntıya neden olan kemoterapötik ilaçlar bulunur. Daha az olumsuz etkiye sahip olma eğiliminde olan fitokimyasallar, uygulanabilir alternatif tedavi seçenekleri arasındadır. Bu çalışma, hesaplamalı biyoloji yaklaşımlarını kullanarak Wnt sinyal yolunda yer alan proteinleri hedefleyerek Gentiana dinarica'da bulunan fitokimyasalların kolorektal kanser tedavisi için potansiyelini araştırmaktadır. Sonuçlarımıza göre, β-catenin, DVL1 ve WNT5a proteinlerine karşı en yüksek bağlanma afinitesini gösteren umut verici bir aday olarak gentioside'i belirlerken, isoorientin COX2 proteinine karşı en büyük potansiyeli göstermektedir. Ancak, gentioside ve isoorientin tarafından ilaç benzerliği kurallarının ihlal edilmesi nedeniyle norswertianin ve gentiopikrozid için ileri analizler yapıldı. Bu bileşikler yüksek bağlanma afinitesi ve uygun ilaç benzerliği profilleri sergiler ve bu da onları Wnt yolağı reseptörlerini inhibe etmek için güçlü adaylar yapar. Bu fitokimyasalların kolorektal kanser tedavisindeki etkinliğini doğrulamak için kapsamlı in vitro ve in vivo çalışmalar önerilmektedir.

Keywords

• Kolorektal kanser
• Gentiana dinarica
• fitokimyasallar
• hesaplamalı biyoloji

Investigation of phytochemicals derived from Gentiana dinarica as potential drug candidates for colorectal cancer by computational approaches

Abstract

Colorectal cancer is one of the deadliest cancers worldwide, necessitating early intervention for the most promising outcomes. Current treatments include chemotherapeutic drugs, which, although effective in reducing the risk of metastasis, often harm healthy cells and cause significant patient distress due to adverse side effects. Phytochemicals, which tend to have fewer negative effects, may serve as viable alternative treatment options. This study investigates the potential of phytochemicals derived from Gentiana dinarica for colorectal cancer treatment by targeting proteins involved in the Wnt signaling pathway using computational biology approaches. Our results identify gentioside as a promising candidate, showing the highest binding affinity toward β-catenin, DVL1, and WNT5a proteins, while isoorientin demonstrates the greatest potential against the COX2 protein. However, due to violations of drug-likeness rules by gentioside and isoorientin, norswertianin and gentiopicroside were further analyzed. These compounds exhibit high binding affinity and favorable drug-likeness profiles, making them strong candidates for inhibiting Wnt pathway receptors. Comprehensive in vitro and in vivo studies are recommended to validate the effectiveness of these phytochemicals in the treatment of colorectal cancer.

Keywords

• Colorectal Cancer
• Gentiana Dinarica
• Phytochemicals
• Computational Biology

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