MUSHROOM DERIVED COMPOUNDS UNVEILED NARINGIN AS A POTENTIAL MULTI-TARGETED ANTI-BREAST CANCER COMPOUND - AN IN-SILICO APPROACH

Yıl 2025, Cilt: 49 Sayı: 1, 21 - 41, 20.01.2025

Ravichandran Veerasamy , Raghuraman Seenivasan , Harish Rajak , Parasuraman Pavadai , Prabha Thangavelu

https://doi.org/10.33483/jfpau.1512113

Öz

Objective: The study aimed to evaluate the multiple target effect of phytochemicals of mushroom against breast cancer using molecular docking and dynamics approach.
Material and Method: In this study, the binding affinity of forty mushroom phytochemicals with various breast cancer proteins such as epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), topoisomerase IIα and topoisomerase IIβ were investigated by docking study using the PyRx tool. The selected receptors are highly cancer influencing and they were selected based on literature. Further molecular dynamics studies were also carried out to confirm the stability and conformation of the naringin-protein complex. In-silico ADMET studies were also carried out to confirm the pharmacokinetic properties and toxicity of the mushroom phytochemicals.
Result and Discussion: From the results obtained, colossolactone G, antcin-A, and formipinioside had higher affinity to EGFR than normal neratinib. Furthermore, fomitoside K, naringin and antcin-A were found to have higher binding affinity than neratinib with HER2. Besides, ergone, naringin, and ergosterol showed higher binding affinity than doxorubicin during interactions with topoisomerase IIα. On the other hand, antrocin, ergosterol peroxide and naringin demonstrated higher binding affinity against topoisomerase IIβ than doxorubicin. Further molecular dynamics studies were also carried out to confirm the stability and conformation of the naringin-protein complex which revealed the best binding score against all the four tested enzymes. Overall, this study suggests naringin as the best ligand and may have great potential in breast cancer protein inhibitors development. To demonstrate their therapeutic promise against breast cancer, more in vitro and in vivo research might be required.

Anahtar Kelimeler

Breast cancer, molecular docking, molecular dynamics, mushroom, naringin

MANTAR TÜRETİLMİŞ BİLEŞİKLER, NARİNGİN'İN POTANSİYEL ÇOK HEDEFLİ MEME KANSERİ KARŞITI BİR BİLEŞİK OLDUĞUNU ORTAYA ÇIKARDI - BİR İN-SİLİCO YAKLAŞIMI

Öz

Amaç: Çalışma, mantar fitokimyasallarının meme kanserine karşı çoklu hedef etkisini moleküler yerleştirme ve dinamik yaklaşımı kullanarak değerlendirmeyi amaçladı.
Gereç ve Yöntem: Bu çalışmada PyRx aracını kullanarak kırk mantar fitokimyasalının epidermal büyüme faktörü reseptörü (EGFR), insan epidermal büyüme faktörü reseptörü 2 (HER2), topoizomeraz IIα ve topoizomeraz IIβ gibi çeşitli meme kanseri proteinlerine bağlanma afinitesi docking çalışmasıyla araştırıldı. Seçilen reseptörler yüksek oranda kansere etki etmektedir ve literatüre dayanılarak seçilmiştir. Naringin-protein kompleksinin stabilitesini ve konformasyonunu doğrulamak için daha ileri moleküler dinamik çalışmalar da yapıldı. Mantar fitokimyasallarının farmakokinetik özelliklerini ve toksisitesini doğrulamak için in-silico ADMET çalışmaları da yapıldı.
Sonuç ve Tartışma: Elde edilen sonuçlara göre kolossolakton G, antcin-A ve formipiniosidin EGFR'ye afinitesi normal neratinib'e göre daha yüksekti. Ayrıca fomitosid K, naringin ve antcin-A'nın HER2 ile neratinibden daha yüksek bağlanma afinitesine sahip olduğu bulunmuştur. Ayrıca ergon, naringin ve ergosterol, topoizomeraz IIα ile etkileşimler sırasında doksorubisinden daha yüksek bağlanma afinitesi göstermiştir. Öte yandan antrosin, ergosterol peroksit ve naringin topoizomeraz IIβ'ya karşı doksorubisinden daha yüksek bağlanma afinitesi göstermiştir. Test edilen dört enzimin tümüne karşı en iyi bağlanma skorunu ortaya koyan naringin-protein kompleksinin stabilitesini ve konformasyonunu doğrulamak için daha ileri moleküler dinamik çalışmalar da yapıldı. Genel olarak bu çalışma, naringinin en iyi ligand olduğunu ve meme kanseri protein inhibitörlerinin geliştirilmesinde büyük potansiyele sahip olabileceğini öne sürüyor. Meme kanserine karşı tedavi vaatlerini göstermek için daha fazla in vitro ve in vivo araştırmaya ihtiyaç duyulabilir.

Anahtar Kelimeler

Mantar, meme kanseri, moleküler dinamik, moleküler kenetlenme, naringin

Kaynakça

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