Conformational, Toxic, Physicochemical and Molecular Docking Analysis of the Anticancer Acalabrutinib Molecule

Year 2022, , 1 - 9, 17.06.2022

Sefa Çelik , A. Demet Demirag , Samet Arslan , Ayşen Özel , Sevim Akyüz

https://doi.org/10.56171/ojn.1004702

Cited By: 1

Abstract

Acalabrutinib is an inhibitor of Bruton's tyrosine kinase (BTK) activity and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. For having these properties acalabrutinib recently was approved for medical use as an anticancer drug. Determining the conformational properties of a bioactive molecule is necessary to reveal its bioactivity. For this reason, the conformational states of the acalabrutinib were examined first. The AM1, a semi-experimental method, was used to examine the stable conformations of the acalabrutinib molecule. Nine lowest energy conformers of the acalabrutinib molecule were determined and their relative energies were calculated. Afterwards, the interactions of the most stable conformer of acalabrutinib with DNA and integrin were examined by docking simulations, and the most active interaction sites and binding affinities were determined.

Keywords

Acalabrutinib, Conformational analysis, Anticancer, Molecular Docking Analysis, Physicochemical Features

Supporting Institution

IOCENS Gümüşhane University International Online Conference on ENGINEERING and NATURAL SCIENCES

Antikanser Acalabrutinib Molekülünün Konformasyonel, Toksik, Fizikokimyasal ve Moleküler Kenetlenme Analizi

Abstract

Acalabrutinib, Bruton'un tirozin kinaz (BTK) aktivitesinin bir inhibitörüdür ve B hücresi antijen reseptörü (BCR) sinyal yolunun aktivasyonunu önler. Acalabrutinib bu özelliklere sahip olduğu için yakın zamanda bir antikanser ilacı olarak tıbbi kullanım için onaylanmıştır. Biyoaktif bir molekülün konformasyonel özelliklerinin belirlenmesi, biyoaktivitesini ortaya çıkarmak için gereklidir. Bu nedenle öncelikle acalabrutinib'in konformasyonel durumları incelenmiştir. Acalabrutinib molekülünün kararlı yapılarını incelemek için yarı deneysel bir yöntem olan AM1 kullanılmıştır. Acalabrutinib molekülünün en düşük enerjili dokuz konformeri belirlenmiştir ve bağıl enerjileri hesaplanmıştır. Daha sonra acalabrutinib'in en kararlı konformerinin DNA ve integrin ile etkileşimleri kenetlenme simülasyonları ile incelenmiş ve en aktif etkileşim bölgeleri ve bağlanma afiniteleri belirlenmiştir.

Keywords

Acalabrutinib, Konformasyon analizi, Antikanser, Moleküler Kenetlenme Analizi, Fizikokimyasal özellikler

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