Synthesis and biological evaluation of fluoro-substituted spiro-isoxazolines as potential anti-viral and anti-cancer agents.

Electrophilic fluorine-mediated dearomative spirocyclization has been developed to synthesize a range of fluoro-substituted spiro-isoxazoline ethers and lactones. The in vitro biological assays of synthesized compounds were probed for anti-viral activity against human cytomegalovirus (HCMV) and cytotoxicity against glioblastomas (GBM6) and triple negative breast cancer (MDA MB 231). Interestingly, compounds 4d and 4n showed significant activity against HCMV (IC 50 ∼ 10 μM), while 4l and 5f revealed the highest cytotoxicity with IC 50 = 36 to 80 μM. The synthetic efficacy and biological relevance offer an opportunity to further drug-discovery development of fluoro-spiro-isoxazolines as novel anti-viral and anti-cancer agents.