Synthesis, anticancer activity and molecular modeling study of novel substituted triazole linked tetrafluoronaphthalene hybrid derivatives.

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 was designed and synthesized CuAAC reaction ' of tetrafluoronaphthalene based terminal alkyne with substituted organic azides. The structural characterizations of the targeted Click products were confirmed by FTIR, H NMR, F NMR, C 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 and 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 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 and . The compounds and may be potential inhibitor candidates in place of a reference inhibitor. A pharmacophore model was generated with the most potent compound , and the approved drugs were screened using the modules of Discovery Studio to find similar drugs. Consequently, this comprehensive study encompassing design, synthesis, and 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.