Laboratory for Chiral Technologies, Scientific Center of Excellence for Marine Bioprospecting-BioProCro, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia.
Laboratory for Machine Learning and Knowledge Representation, Division of Electronics, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia.
Mar Drugs. 2024 Jul 3;22(7):310. doi: 10.3390/md22070310.
The total synthesis of two new marine natural products, (±)-marinoaziridine B and (±)--methyl marinoaziridine A , was accomplished. The (±)-marinoaziridine was prepared in a six-step linear sequence with a 2% overall yield. The key steps in our strategy were the preparation of the chiral epoxide (±)- using the Johnson Corey Chaykovsky reaction, followed by the ring-opening reaction and the Staudinger reaction. The ,-dimethylation of compound (±)- gives (±)--methyl marinoaziridine A . The NMR spectra of synthetized (±)-marinoaziridine B and isolated natural product did not match. The compounds are biologically characterized using relevant in silico, in vitro and in vivo methods. In silico ADMET and bioactivity profiling predicted toxic and neuromodulatory effects. In vitro screening by MTT assay on three cell lines (MCF-7, H-460, HEK293T) showed that both compounds exhibited moderate to strong antiproliferative and cytotoxic effects. Antimicrobial tests on bacterial cultures of and demonstrated the dose-dependent inhibition of the growth of both bacteria. In vivo toxicological tests were performed on zebrafish and showed a significant reduction of zebrafish mortality due to -methylation in (±)-.
两种新型海洋天然产物（±）- Marinoaziridine B 和（±）--甲基 Marinoaziridine A 的全合成已经完成。（±）- Marinoaziridine 是通过六步线性序列以 2%的总产率制备的。我们策略中的关键步骤是使用 Johnson Corey Chaykovsky 反应制备手性环氧化物（±）-，然后进行开环反应和 Staudinger 反应。（±）-化合物的，-二甲基化得到（±）--甲基 Marinoaziridine A。合成的（±）- Marinoaziridine B 和分离的天然产物的 NMR 光谱不匹配。使用相关的计算、体外和体内方法对化合物进行了生物特征描述。计算 ADMET 和生物活性分析预测了毒性和神经调节作用。在三种细胞系（MCF-7、H-460、HEK293T）上进行的 MTT 测定体外筛选表明，这两种化合物都表现出中等至强的抗增殖和细胞毒性作用。对 和 的细菌培养物进行的抗菌测试表明，两种细菌的生长都表现出剂量依赖性抑制。在斑马鱼 上进行的体内毒理学测试表明，（±）-中的 -甲基化显著降低了斑马鱼的死亡率。
