Editor-in-Chief İlkay Küçükgüzel Associate Editor Aslı Türe Online ISSN 2630-6344 Publisher Marmara University Frequency Bimonthly (Six issues / year) Abbreviation J.Res.Pharm. Former Name Marmara Pharmaceutical Journal
Journal of Research in Pharmacy 2020 , Vol 24 , Issue 4
Synthesis, in silico studies and cytotoxicity evaluation of novel 1,3,4-oxadiazole derivatives designed as potential mPGES-1 inhibitors
Gizem ERENSOY1,Kai DING2,Chang-Guo ZHAN2,Ammar ELMEZAYEN4,Kemal YELEKÇİ4,Merve DURACIK5,Özlem BİNGÖL ÖZAKPINAR5,İlkay KÜÇÜKGÜZEL1
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, Haydarpaşa 34668 İstanbul, Turkey.
2Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, United States
3Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, United States
4Department of Bioinformatics and Genetics, Faculty of Engineering and Natural Sciences, Kadir Has University, İstanbul, Turkey
5Department of Biochemistry, Faculty of Pharmacy, Marmara University, Haydarpaşa 34668 İstanbul, Turkey
DOI : 10.35333/jrp.2020.187 series of new 1,3,4-oxadizole derivatives containing thioether group, has been synthesized to investigate their mPGES-1 inhibitory activities. The synthesized compounds were also evaluated for their anticancer and COX-1/2 inhibitory activities. All compounds were checked for their purity using TLC and HPLC analyses. The melting points, elemental analysis, FT-IR, 1H-/13C-NMR and LR-MS data were utilized for structural characterization. The most potent derivative was 2-[5-{[2-methyl-5-(propan-2-yl)phenoxy]methyl}-1,3,4-oxadiazol-2-yl)sulphanyl]-1-(phenyl)ethan-1-one 3a, which showed inhibitory activity against mPGES-1 with an IC50 of 4.95 μM. Docking studies with mPGES-1 and COX-1/2 enzymes revealed their affinity and potential binding mechanism for the tested compounds. Keywords : 1,3,4-Oxadiazoles; thioethers; mPGES-1 inhibition; COX-1/2 inhibition; anticancer activity; molecular docking; ADME prediction.
Marmara University