School of Pharmacy, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau 999078, China.
Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL 60115, USA.
Molecules. 2020 Oct 14;25(20):4697. doi: 10.3390/molecules25204697.
In comparison with pristine sinomenine and carborane precursors, the calculations of molecular docking with matrix metalloproteinases (MMPs) and methylcarboranyl--butyl sinomenine showed improved interactions. Accordingly, methylcarboranyl--butyl sinomenine shows a high potential in the treatment of rheumatoid arthritis (RA) in the presence of slow neutrons. The reaction of potassium salt of sinomenie, which is generated from the deprotonation of sinomenine () using potassium carbonate in a solvent of ,-dimethyl formamide, with 4-methylcarboranyl--butyl iodide, () forms methylcarboranyl--butyl sinomenine () in 54.3% yield as a new product. This new compound was characterized by H, C, and B NMR spectroscopy, FT-IR spectroscopy, and elemental analyses to confirm its molecular composition. In addition to molecular docking interactions with MMPs, the in vitro killing effects of , along with its toxicity measurements, exhibited its potential to be the new drug delivery agent for boron neutron capture synovectomy (BNCS) and boron neutron capture therapy (BNCT) for the treatment of rheumatoid arthritis (RA) and cancers in the presence of slow neutrons, respectively.
与原始的青藤碱和碳硼烷前体相比，对接基质金属蛋白酶（MMPs）和甲基碳硼基-丁基青藤碱的分子计算显示出了更好的相互作用。因此，在慢中子存在的情况下，甲基碳硼基-丁基青藤碱在治疗类风湿性关节炎（RA）方面具有很高的潜力。青藤碱的钾盐（）是由青藤碱（）在碳酸钾的作用下在 - 二甲基甲酰胺溶剂中脱质子化生成的，与 4-甲基碳硼基-丁基碘化盐（）反应，以 54.3%的产率形成新产物甲基碳硼基-丁基青藤碱（）。该新化合物通过 1H、13C 和 11B NMR 光谱、FT-IR 光谱和元素分析进行了表征，以确认其分子组成。除了与 MMPs 的分子对接相互作用外，还对其体外杀伤效果及其毒性进行了测量，表明其有可能成为硼中子俘获滑膜切除术（BNCS）和硼中子俘获治疗（BNCT）的新型药物输送剂，分别用于治疗类风湿性关节炎（RA）和癌症，以及在慢中子存在的情况下。
