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作为潜在抗病毒和抗癌药物的氟取代螺异恶唑啉的合成及生物学评价

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

作者信息

Das Prasanta, Boone Sarah, Mitra Dipanwita, Turner Lindsay, Tandon Ritesh, Raucher Drazen, Hamme Ashton T

机构信息

Department of Chemistry and Biochemistry, Jackson State University Jackson Mississippi 39217 USA

Department of Microbiology and Immunology, University of Mississippi Medical Center Jackson Mississippi 39216 USA.

出版信息

RSC Adv. 2020 Aug 17;10(50):30223-30237. doi: 10.1039/d0ra06148d. eCollection 2020 Aug 10.

Abstract

Electrophilic fluorine-mediated dearomative spirocyclization has been developed to synthesize a range of fluoro-substituted spiro-isoxazoline ethers and lactones. The 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 ∼ 10 μM), while 4l and 5f revealed the highest cytotoxicity with IC = 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.

摘要

亲电氟介导的去芳构化螺环化反应已被用于合成一系列氟取代的螺异恶唑啉醚和内酯。对合成化合物进行了生物活性测定,以检测其对人巨细胞病毒(HCMV)的抗病毒活性以及对胶质母细胞瘤(GBM6)和三阴性乳腺癌(MDA MB 231)的细胞毒性。有趣的是,化合物4d和4n对HCMV显示出显著活性(IC ∼ 10 μM),而4l和5f表现出最高的细胞毒性,IC = 36至80 μM。这种合成效率和生物学相关性为进一步将氟代螺异恶唑啉开发为新型抗病毒和抗癌药物提供了机会。

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