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Synthesis, anticancer activity and molecular modeling study of novel substituted triazole linked tetrafluoronaphthalene hybrid derivatives       
Yazarlar
Doç. Dr. Musa ERDOĞAN Doç. Dr. Musa ERDOĞAN
Kafkas Üniversitesi, Türkiye
Ferah Cömert Önder
Türkiye
Özet
To create some novel anticancer molecules, a library of novel series of various triazoles linked to the hydroxyl group of 5,6,7,8-tetrafluoronaphthalen-1-ol (3) was designed and synthesized via CuAAC reaction ‘Click Chemistry’ of tetrafluoronaphthalene based terminal alkyne with substituted organic azides. The structural characterizations of the targeted Click products 9–18 were confirmed by FTIR, 1H NMR, 19F NMR, 13C NMR and HRMS spectroscopy. Synthesized compounds were tested in two triple negative breast cancer (TNBC) cell lines to understand their anticancer potentials. According to our findings, compounds 14 and 13 showed high cytotoxicity in BT549 cells at 20 μM and 30 μM, respectively. Moreover, these compounds blocked the migration of BT549 cells. In the MDA-MB-231 cell line, compound 18 exhibited high cytotoxicity and can block cell migration for 24 h. Molecular docking study with synthesized novel compounds was performed by Glide/SP method against SphK1 drug target. Furthermore, molecular dynamics (MD) simulation was carried out for the compounds 12–14 and 18. The compounds 13 and 14 may be potential inhibitor candidates in place of a reference inhibitor. A pharmacophore model was generated with the most potent compound 14, and the approved drugs were screened using the modules of Discovery Studio to find similar drugs. Consequently, this comprehensive study encompassing design, synthesis, in vitro and in silico analyses were correlated with the structure-activity relationship between compounds. The findings have the potential to unveil promising drug candidates for future studies. Communicated by Ramaswamy H. Sarma.
Anahtar Kelimeler
ADMET | anticancer activity | Click chemistry | molecular docking | molecular dynamics (MD) simulation | tetrafluoronaphthalene | triazole
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı Journal of Biomolecular Structure and Dynamics
Dergi ISSN 0739-1102
Dergi Tarandığı Indeksler SCI-Expanded
Dergi Grubu Q1
Makale Dili Türkçe
Basım Tarihi 10-2024
Cilt No 42
Sayı 18
Sayfalar 9767 / 9786
Doi Numarası 10.1080/07391102.2023.2252914
Makale Linki http://dx.doi.org/10.1080/07391102.2023.2252914