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

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

Makale detayları

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

Yazarlar:

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

Yayıncı:

Ankara University

Ana Başlıklar:

Farmasotik Kimya | Eczacılık ve İlaç Bilimleri (Diğer)

Dergi:

Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.49 Issue 1, pp.21-41

Belge Tipi:

Makale

Yayın Tarihi:

1/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001333045

pISSN:

1015-3918

Anahtar kelimeler:

Özet:

 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.

 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.

 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.

 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 EGFRye afinitesi normal neratinibe göre daha yüksekti. Ayrıca fomitosid K, naringin ve antcin-Anın 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 IIβya 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.

Makale detayları

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

Yazarlar:

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

Yayıncı:

Ankara University

Ana Başlıklar:

Farmasotik Kimya | Eczacılık ve İlaç Bilimleri (Diğer)

Dergi:

Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.49 Issue 1, pp.21-41

Belge Tipi:

Makale

Yayın Tarihi:

1/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001333045

pISSN:

1015-3918

Breast cancer

molecular docking

molecular dynamics

mushroom

naringinMantar

meme kanseri

moleküler dinamik

moleküler kenetlenme

naringin

Sayı

Makale detayları

Yazarlar: Ravichandran Veerasamy | Raghuraman Seenivasan | Harish Rajak | Parasuraman Pavadai | Prabha Thangavelu

Yayıncı: Ankara University

Ana Başlıklar: Farmasotik Kimya | Eczacılık ve İlaç Bilimleri (Diğer)

Dergi: Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.49 Issue 1, pp.21-41

Belge Tipi: Makale

Yayın Tarihi: 1/2025

Belge Dili: İngilizce

Document ID (Org No.): 2001333045

pISSN: 1015-3918

Sayı

Yazarlar:

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

Yayıncı:

Ankara University

Ana Başlıklar:

Farmasotik Kimya | Eczacılık ve İlaç Bilimleri (Diğer)

Dergi:

Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.49 Issue 1, pp.21-41

Belge Tipi:

Makale

Yayın Tarihi:

1/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001333045

pISSN:

1015-3918