The natural and synthetic peroxides, containing an endo-peroxide or spiro-peroxides, have attracted significant attention by virtue of their diverse and interesting biological activities. Since the discovery, artemisinin (Qinghaosu), artemisinin-derived hybrid molecules, and dimmers were conspicuously known to exhibit potent antimalarial, anthelmintic, antiprotozoal, fungicidal, antiviral, antibacterial, and anticancer activities. Similarly, isoxazolines and its unique spiro-motifs were found to be ubiquitous in natural products and many synthetic drugs to show pivotal biological activities. In this context, we previously showcased our interest toward isoxazoline containing bromotyrosine natural products and small spiro-isoxazolines, pertaining to various heterocycles, as potential anticancer agents. In this context, isoxazoles and cyclic-peroxides were tethered chemically to construct a novel class of spiro-isoxazoline-peroxide. A concise and efficient strategy has been demonstrated to access an array of aromatic or amide substituted isoxazoline-peroxides. The synthetic compounds were evaluated for in vitro antiviral and anticancer activity against human cytomegalovirus (HCMV) and glioblastoma cell line (GBM6). Notably, one of the synthetic analogues displayed potent anticytomegaloviral activity (IC50 = 19 µM) with regard to the ganciclovir (GCV) which is the standard drug used for the treatment of antiviral disease. Surprisingly, an independent biological assay for this compound also revealed its antiproliferative activity against human glioblastoma cell line (GBM6) with IC50 = 10µm. Therefore, the unity of isoxazoline and peroxide developed a novel class of peroxide scaffold that could be therapeutic potential against cytomegalovirus (HCMV) replication and glioblastoma cell (GBM6).

Design, synthesis, and biological evaluation of novel spiro-isoxazoline-peroxides as potent inhibitors of human-cytomegalovirus (HCMV) and glioblastoma cell (GBM6)

2019 Spring National Meeting

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