新型氨基哒嗪衍生物米那普仑经辐射修饰后，在 LPS 刺激的 RAW 264.7 和 DH82 巨噬细胞中表现出强大的抗炎作用。
Novel aminopyridazine derivative of minaprine modified by radiolysis presents potent anti-inflammatory effects in LPS-stimulated RAW 264.7 and DH82 macrophage cells.
机构信息
Research Division for Biotechnology, Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute (KAERI), Jeongeup, 56212, Republic of Korea.
Center for Companion Animal New Drug Development, Korea Institute of Toxicology (KIT), Jeongeup, 56212, Republic of Korea.
出版信息
Sci Rep. 2023 Jul 5;13(1):10887. doi: 10.1038/s41598-023-37812-8.
Radiation molecularly transforms naturally occurring products by inducing the methoxylation, hydroxylation, and alkylation of parent compounds, thereby affecting the anti-inflammatory capacities of those compounds. Minaprine (1) modified by ionizing radiation generated the novel hydroxymethylation hydropyridazine (2), and its chemical structure was determined based on NMR and HRESIMS spectra. Compared to the original minaprine, the novel generated product showed a highly enhanced anti-inflammatory capacity inhibited nitric oxide (NO) and prostaglandin E (PGE) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 and DH82 macrophage cells. In addition, minaprinol (2) effectively inhibited cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) at the protein level and pro-inflammatory cytokine (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-10) production in macrophages.
辐射通过诱导母体化合物的甲氧基化、羟化和烷基化，将天然产物分子转化，从而影响这些化合物的抗炎能力。经电离辐射修饰的米那普仑（1）生成了新型的羟甲基化哒嗪（2），并基于 NMR 和 HRESIMS 谱确定了其化学结构。与原始米那普仑相比，新型生成的产物表现出高度增强的抗炎能力，抑制脂多糖（LPS）刺激的 RAW 264.7 和 DH82 巨噬细胞中一氧化氮（NO）和前列腺素 E（PGE）的产生。此外，米那普醇（2）在蛋白水平上有效抑制环氧合酶-2（COX-2）和诱导型一氧化氮合酶（iNOS），并抑制巨噬细胞中促炎细胞因子（肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-10（IL-10））的产生。
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