Department of Organic Chemistry, Faculty of Pharmacy, Wroclaw Medical University, 211A Borowska Street, 50-556 Wroclaw, Poland.
Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Rudolf Weigl Street, 53-114 Wroclaw, Poland.
Molecules. 2020 Aug 4;25(15):3558. doi: 10.3390/molecules25153558.
The synthesis of a series of novel 7-aminooxazolo[5,4-]pyrimidines , transformations during their synthesis and their physicochemical characteristics have been described. Complete detailed spectral analysis of the intermediates -, the -cyanooxazolylacetamidine by-products and final compounds has been carried out using MS, IR, 1D and 2D NMR spectroscopy. Theoretical research was carried out to explain the privileged formation of 7-aminooxazolo[5,4-]pyrimidines in relation to the possibility of their isomer formation and the related thermodynamic aspects. Additionally, the single-crystal X-ray diffraction analysis for was reported. Ten 7-aminooxazolo[5,4-]pyrimidines (-) were biologically tested in vitro to preliminarily evaluate their immunological, antiviral and anticancer activity. Compounds and showed the best immunoregulatory profile. The compounds displayed low-toxicity and strongly inhibited phytohemagglutinin A-induced proliferation of human peripheral blood lymphocytes and lipopolysaccharide-induced proliferation of mouse splenocytes. Compound caused also a moderate suppression of tumor necrosis factor α (TNF-α) production in a human whole blood culture. Of note, the compounds also inhibited the growth of selected tumor cell lines and inhibited replication of human herpes virus type-1 (HHV-1) virus in A-549 cell line. Molecular investigations showed that the compounds exerted differential changes in expression of signaling proteins in Jurkat and WEHI-231 cell lines. The activity of is likely associated with elicitation of cell signaling pathways leading to cell apoptosis. The compounds may be of interest in terms of therapeutic utility as inhibitors of autoimmune disorders, virus replication and antitumor agents.
描述了一系列新型 7-氨基-噁唑并[5,4-d]嘧啶的合成、它们在合成过程中的转化以及它们的物理化学特性。对中间体-、-氰基噁唑基乙脒副产物-和最终化合物-进行了完整的详细光谱分析，使用 MS、IR、1D 和 2D NMR 光谱法。进行了理论研究，以解释 7-氨基-噁唑并[5,4-d]嘧啶形成的优势与它们异构化的可能性及其相关的热力学方面有关。此外，还报道了的单晶 X 射线衍射分析。对 10 种 7-氨基-噁唑并[5,4-d]嘧啶（-）进行了体外生物学测试，初步评估了它们的免疫、抗病毒和抗癌活性。化合物 和 显示出最佳的免疫调节特性。这些化合物具有低毒性，并强烈抑制植物血球凝集素 A 诱导的人外周血淋巴细胞增殖和脂多糖诱导的小鼠脾细胞增殖。化合物 还导致人全血培养中肿瘤坏死因子 α（TNF-α）产生适度抑制。值得注意的是，这些化合物还抑制了选定的肿瘤细胞系的生长，并抑制了人疱疹病毒 1 型（HHV-1）在 A-549 细胞系中的复制。分子研究表明，这些化合物在 Jurkat 和 WEHI-231 细胞系中对信号蛋白的表达产生了不同的变化。的活性可能与引发导致细胞凋亡的细胞信号通路有关。这些化合物可能具有治疗应用的潜力，可作为自身免疫疾病、病毒复制和抗肿瘤药物的抑制剂。
