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Published on: June 1, 2022
Design, Synthesis, and Preliminary Studies of Spiro-isoxazoline-peroxides against Human Cytomegalovirus and
Prasanta Das1, Mohammad H Hasan, Dipanwita Mitra
1Department of Chemistry and Biochemistry , Jackson State University , Jackson , Mississippi 39217 , United States.
Abstract:
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.
Insights
Researchers developed novel spiro-isoxazoline peroxides to combat glioblastoma (GBM) and human cytomegalovirus (HCMV). Compound 13m demonstrated promising antiproliferative effects against GBM cells and moderate antiviral activity against HCMV.
Area of Science:
- * Organic Chemistry
- * Medicinal Chemistry
- * Virology
Background:
- * The link between glioblastoma (GBM) and human cytomegalovirus (HCMV) is a long-standing area of research for novel therapeutic strategies.
- * Peroxides, both natural and synthetic, have historically shown potential as antiviral and anticancer agents.
- * Developing new treatments for GBM and HCMV remains a critical unmet medical need.
Purpose of the Study:
- * To synthesize and evaluate a novel class of spiro-isoxazoline peroxides for biological activities.
- * To investigate the in vitro antiviral efficacy against HCMV.
- * To assess the antiproliferative effects on a human glioblastoma cell line (GBM6).
Main Methods:
- * Synthesis of a novel series of peroxides incorporating a spiro-isoxazoline scaffold.
- * In vitro antiviral assays against HCMV.
- * In vitro antiproliferative assays using the GBM6 glioblastoma cell line.
Main Results:
- * Compound 13m exhibited moderate in vitro antiviral activity against HCMV with an IC50 of 19 μM.
- * Compound 13m demonstrated significant antiproliferative activity against the GBM6 glioblastoma cell line with an IC50 of 10 μM.
- * The study identified a promising lead compound with dual potential against HCMV and GBM.
Conclusions:
- * The combination of isoxazoline and peroxide moieties in novel compounds is a viable strategy for drug discovery.
- * Compound 13m represents a potential starting point for developing new therapeutic agents targeting both HCMV infection and glioblastoma.
- * Further research into this class of compounds could lead to effective treatments for HCMV-associated GBM.
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