MS HASTALIĞININ TEDAVİSİ İÇİN YENİ SİKLOFİLİN D RESEPTÖR İNHİBİTÖRLERİNİN GELİŞTİRİLMESİ

Year 2022, , 458 - 473, 29.05.2022

Gozde Yalcin , Birsen Huylu

https://doi.org/10.33483/jfpau.1090546

Cited By: 1

Abstract

Amaç: Bu çalışmada, multipl skleroz (MS) hastalığında mitokondriyal fonksiyon bozukluğuna neden olan siklofilin D (CypD) reseptörünün inhibisyonu için yeni moleküllerin geliştirilmesine yönelik hesaplamalı çalışmaların yapılması amaçlanmıştır.

Gereç ve Yöntem: Literatür taraması ile tespit edilen CypD inhibitörlerine PharmaGist Web sunucusu üzerinden farmakofor modelleme çalışması uygulanmıştır. PharmaGist'in en iyi farmakofor modellerine göre ZINCPharmer veri tabanından 80 molekül elde edilmiş ve bu moleküllere in silico ADME/Toksikoloji analizi uygulanmıştır. Daha sonra Autodock Vina programı ile ADME/Tox analizleri sonucunda en iyi sonucu veren ligandlar ile moleküler yerleştirme yapılmıştır.

Sonuç ve Tartışma: ZINC00390492 molekülü hem CypD, hem de Sfingosin-1-fosfat reseptörü 1 ile en iyi bağlanma afinitesi ve bağlanma profilini göstermektedir. Bu molekülün, MS tedavisi için bir öncü molekül olabileceği gösterilmiştir.

Keywords

Farmakofor modelleme, in silico, moleküler doking, multipl skleroz, siklofilin D

DEVELOPMENT OF NEW CYCLOPHILIN D RECEPTOR INHIBITORS FOR THE TREATMENT OF MULTIPLE SCLEROSIS

Abstract

Objective: In this study, it was aimed to carry out computational studies for the development of new molecules for the inhibition of the cyclophilin D (CypD) receptor, which causes the disability of mitochondrial function in multiple sclerosis (MS) disease.

Material and Method: Pharmacophore modeling study was applied via the PharmaGist Web server to the CypD inhibitors detected by the literature search. According to the best pharmacophore models from PharmaGist, 80 molecules were obtained from the ZINCPharmer database, and in silico ADME/Toxicology analysis was applied to these molecules. Then, molecular docking was performed with the ligands that gave the best results as a result of ADME/Tox analyses with the Autodock Vina program.

Result and Discussion: ZINC00390492 molecule shows the best binding affinity and binding profile with both CypD, Sphingosine-1-phosphate receptor 1. It has been demonstrated that this molecule may be a lead molecule for the treatment of MS. 

Keywords

Cyclophilin D, in silico, Molecular docking, Multiple Sclerosis, Pharmacophore modeling

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