Design, Synthesis, and Preliminary Studies of Spiro-isoxazoline-peroxides against Human Cytomegalovirus and Glioblastoma

The
association between glioblastoma (GBM) and human cytomegalovirus
(HCMV) infection has been the intensely debated topic over the decades
for developing new therapeutic options. In this regard, the peroxides
from natural and synthetic sources served as potential antiviral and
anticancer agents in the past. Herein, a concise and efficient strategy
has been demonstrated to access a novel class of peroxides containing
a spiro-isoxazoline to primarily investigate the biological activities.
The synthetic compounds were evaluated for in vitro antiviral and
antiproliferative activity against HCMV and glioblastoma cell line
(GBM6), respectively. While compound 13m showed moderate
anti-CMV activity (IC50 = 19 μM), surprisingly, an
independent biological assay for compound 13m revealed
its antiproliferative activity against the human glioblastoma cell
line (GBM6) with an IC50 of 10 μM. Hence, the unification
of an isoxazoline and peroxide heterocycles could be a potential direction
to initiate the HCMV-GBM drug discovery program.