DEVELOPMENT OF NEW CYCLOPHILIN D RECEPTOR INHIBITORS FOR THE TREATMENT OF MULTIPLE SCLEROSIS MS HASTALIĞININ TEDAVİSİ İÇİN YENİ SİKLOFİLİN D RESEPTÖR İNHİBİTÖRLERİNİN GELİŞTİRİLMESİ

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YALÇIN ÖZKAT G., Huylu B.

Ankara Universitesi Eczacilik Fakultesi Dergisi, cilt.46, sa.2, ss.458-473, 2022 (Scopus) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 46 Sayı: 2
  • Basım Tarihi: 2022
  • Doi Numarası: 10.33483/jfpau.1090546
  • Dergi Adı: Ankara Universitesi Eczacilik Fakultesi Dergisi
  • Derginin Tarandığı İndeksler: Scopus, Central & Eastern European Academic Source (CEEAS), EMBASE, TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.458-473
  • Anahtar Kelimeler: Cyclophilin D, in silico, molecular docking, multiple sclerosis, pharmacophore modeling
  • Recep Tayyip Erdoğan Üniversitesi Adresli: Evet

Özet

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.