Molecular Docking Study of Midostaurin, an Effective Drug in the Treatment of Myeloid Leukemia

Sefa Çelik; Gözde Yılmaz; Ayşen Özel; Sevim Akyüz

doi:10.56171/ojn.1102513

TR EN

Miyeloid Lösemi Tedavisinde Etkili Bir İlaç Olan Midostaurinin Moleküler Kenetlenme Çalışması

Öz

Midostaurin (C35H30N4O4), diğer kemoterapi ajanları ile birlikte bazı akut miyeloid lösemi tiplerini tedavi etmek için kullanılan multi-target kinaz inhibitörüdür. Biyoaktif bir molekülün biyoaktivitesini gösterdiği en kararlı konformerinin belirlenmesinin önemi dolayısıyla ilk olarak Midostaurin’in yapısal tercihleri bulunup değerlendirilmiştir. Midostaurin molekülünün konformasyonel analizi, yarı deneysel bir metot olan PM3 kullanılarak yapılmıştır. En kararlı üç konformer ve bunların bağıl enerjileri belirlenmiştir. Bütünleyici bir zar proteini olan Epitermal Büyüme faktörü reseptörü (EGFR) ve aşırı ekspresyonu, çok çeşitli tümörlerin gelişimi ile ilişkilidir. Bu nedenle, EGFR inhibitörleri, EGFR eksprese eden tümörlerin büyümesini önleyerek ve hastaların hayatta kalma oranlarını artırarak antikanser ilaçlar olarak işlev görebilir. Ek olarak, DNA antikanser ilaçlar için önemli bir hedeftir. Midostaurin’in antikanser özelliklerini aydınlatmak için EGFR ve DNA’ya karşı moleküler kenetlenme simülasyonları yapılmıştır. Ligand-hedef reseptör komplekslerinin bağlanma modları ve bağlanma afiniteleri belirlenmiştir. Midostaurin, DNA (ΔG = -8.6 kcal/mol) ve EGFR (ΔG = - 9.6 kcal/mol) ile güçlü bağlanma afinitesi göstermiştir. Sonuçlar, Midostaurin'in önemli anti-tümör etkisini ortaya çıkarmıştır.

Anahtar Kelimeler

Konformasyon analizi, DNA, EGFR, Midostaurin, moleküler kenetlenme

Molecular Docking Study of Midostaurin, an Effective Drug in the Treatment of Myeloid Leukemia

Öz

Midostaurin (C35H30N4O4) is a multi-target kinase inhibitor used to treat some types of acute myeloid leukemia in combination with other chemotherapy agents. Firstly, the structural preferences of the Midostaurin were evaluated due to the importance to determine the most stable conformer of a bioactive molecule to elucidate its bioactivity. The conformational analysis of the Midostaurin molecule was performed using the PM3, a semi-experimental method. The three most stable conformers and their relative energies were determined. The Epidermal Growth Factor receptor (EGFR) is an integral membrane protein, and its over-expression is associated with the development of a wide variety of tumors. For this reason, EGFR inhibitors can act as anticancer drugs as preventing the growth of EGFR-expressing tumors and increasing the survival rates of patients. On the other hand, DNA is an important target for anticancer drugs. To elucidate the anticancer properties of Midostaurin, the molecular docking simulations were performed against EGFR and DNA targets. The binding modes and binding affinities of the ligand-target receptor complexes were determined. Midostaurin showed strong binding affinity to DNA (G = -8.6 kcal/mol) and EGFR (G = - 9.6 kcal/mol). The results revealed the significant anti-tumor effect of Midostaurin.

Anahtar Kelimeler

Conformational analysis, DNA, EGFR, Midostaurin, molecular docking

Destekleyen Kurum

Research funds of Istanbul University

Proje Numarası

ÖNAP-2423

Kaynakça

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Ayrıntılar

Birincil Dil

İngilizce

Konular

-

Bölüm

Araştırma Makalesi

Yazarlar

Sefa Çelik ^*
0000-0001-6216-1297
Türkiye

Gözde Yılmaz
0000-0002-8000-2385
Türkiye

Ayşen Özel
0000-0002-8680-8830
Türkiye

Sevim Akyüz
0000-0003-3313-6927
Türkiye

Yayımlanma Tarihi

30 Haziran 2023

Gönderilme Tarihi

12 Nisan 2022

Kabul Tarihi

14 Temmuz 2022

Yayımlandığı Sayı

Yıl 2023 Cilt: 8 Sayı: 1

DOI

https://doi.org/10.56171/ojn.1102513

IZ

https://izlik.org/JA35FK42UJ

APA

Çelik, S., Yılmaz, G., Özel, A., & Akyüz, S. (2023). Molecular Docking Study of Midostaurin, an Effective Drug in the Treatment of Myeloid Leukemia. Open Journal of Nano, 8(1), 2-10. https://doi.org/10.56171/ojn.1102513

AMA

1.Çelik S, Yılmaz G, Özel A, Akyüz S. Molecular Docking Study of Midostaurin, an Effective Drug in the Treatment of Myeloid Leukemia. Open J. Nano. 2023;8(1):2-10. doi:10.56171/ojn.1102513

Chicago

Çelik, Sefa, Gözde Yılmaz, Ayşen Özel, ve Sevim Akyüz. 2023. “Molecular Docking Study of Midostaurin, an Effective Drug in the Treatment of Myeloid Leukemia”. Open Journal of Nano 8 (1): 2-10. https://doi.org/10.56171/ojn.1102513.

EndNote

Çelik S, Yılmaz G, Özel A, Akyüz S (01 Haziran 2023) Molecular Docking Study of Midostaurin, an Effective Drug in the Treatment of Myeloid Leukemia. Open Journal of Nano 8 1 2–10.

IEEE

[1]S. Çelik, G. Yılmaz, A. Özel, ve S. Akyüz, “Molecular Docking Study of Midostaurin, an Effective Drug in the Treatment of Myeloid Leukemia”, Open J. Nano, c. 8, sy 1, ss. 2–10, Haz. 2023, doi: 10.56171/ojn.1102513.

ISNAD

Çelik, Sefa - Yılmaz, Gözde - Özel, Ayşen - Akyüz, Sevim. “Molecular Docking Study of Midostaurin, an Effective Drug in the Treatment of Myeloid Leukemia”. Open Journal of Nano 8/1 (01 Haziran 2023): 2-10. https://doi.org/10.56171/ojn.1102513.

JAMA

1.Çelik S, Yılmaz G, Özel A, Akyüz S. Molecular Docking Study of Midostaurin, an Effective Drug in the Treatment of Myeloid Leukemia. Open J. Nano. 2023;8:2–10.

MLA

Çelik, Sefa, vd. “Molecular Docking Study of Midostaurin, an Effective Drug in the Treatment of Myeloid Leukemia”. Open Journal of Nano, c. 8, sy 1, Haziran 2023, ss. 2-10, doi:10.56171/ojn.1102513.

Vancouver

1.Sefa Çelik, Gözde Yılmaz, Ayşen Özel, Sevim Akyüz. Molecular Docking Study of Midostaurin, an Effective Drug in the Treatment of Myeloid Leukemia. Open J. Nano. 01 Haziran 2023;8(1):2-10. doi:10.56171/ojn.1102513

Open Journal of Nano(OJN), dergisi molekülerden mikro boyuttaki yapılara kadar değişen fiziksel, kimyasal ve biyolojik olaylar ve süreçlerle ilgili (ancak bunlarla sınırlı olmayan) bilgilerle ilgilenir.
The Open Journal of Nano dergisinde yayınlanan tüm yayınlar Atıf-GayriTicari 4.0 Uluslararası (CC BY-NC 4.0) lisansı altında lisanlanmıştır.

Miyeloid Lösemi Tedavisinde Etkili Bir İlaç Olan Midostaurinin Moleküler Kenetlenme Çalışması

Öz

Anahtar Kelimeler

Molecular Docking Study of Midostaurin, an Effective Drug in the Treatment of Myeloid Leukemia

Öz

Anahtar Kelimeler

Destekleyen Kurum

Proje Numarası

Kaynakça

Ayrıntılar

Birincil Dil

Konular

Bölüm

Yazarlar

Yayımlanma Tarihi

Gönderilme Tarihi

Kabul Tarihi

Yayımlandığı Sayı

DOI

IZ

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