分析了一系列衍生自 5-氨基尿嘧啶和取代水杨醛的水杨基尿嘧啶 (1-18) 的细胞毒性活性和酶抑制效力。十八个衍生物中的九个（6-8、10、12-15、18）是本工作中首次合成的新型分子，其他衍生物是我们课题组之前合成的。通过质子核磁共振、碳核磁共振、傅里叶变换红外光谱和元素分析对化合物进行了表征。所有化合物均针对 PC-3（人前列腺腺癌）、A549（人肺泡腺癌）和 SHSY-5Y（人神经母细胞瘤）癌细胞系以及非致瘤性 HEK293（人胚胎肾细胞）细胞系进行了体外细胞毒性测试。 3,5-二叔丁基水杨醛衍生的化合物 (8) 对 PC-3 人前列腺腺癌细胞具有毒性，显示出有希望的 IC50 值（7.05±0.76μM）。本研究还旨在评估这些化合物对几种关键酶的抑制作用，即碳酸酐酶 I 和 II（CA I 和 CA II）、乙酰胆碱酯酶（AChE）、丁酰胆碱酯酶（BChE）和谷胱甘肽还原酶（GR）。与各种全球性疾病有关，例如阿尔茨海默病、癫痫、癌症、疟疾、糖尿病和青光眼。通过测定其 Ki 值来评估测试化合物的抑制谱，其范围为：AChE 为 2.96 至 9.24nM，BChE 为 3.78 至 12.57nM，CA I 为 8.42 至 25.74nM，CA II 为 7.24 至 19.74nM，CA II 为 0.541 GR 为 1.124 μM。还对所有化合物进行了分子对接研究。与临床使用的标准相比，大多数衍生物表现出更有效的抑制作用。因此，我们的研究结果表明，本研究中提出的水杨基衍生物是有前途的候选药物，需要进一步评估。© 2023 作者。 Archiv der Pharmazie 由 Wiley-VCH GmbH 代表 Deutsche Pharmazeutische Gesellschaft 出版。

A series of salicylidene uracil (1-18) derived from 5-aminouracil and substituted salicylaldehydes were analyzed for cytotoxic activity and enzyme inhibitory potency. Nine out of eighteen derivatives (6-8, 10, 12-15, 18) are novel molecules synthesized for the first time in this work, and other derivatives were previously synthesized by our group. The compounds were characterized by Proton nuclear magnetic resonance, carbon nuclear magnetic resonance, fourier transform infrared spectroscopy, and elemental analysis. All compounds were tested for their in vitro cytotoxicity against PC-3 (human prostate adenocarcinoma), A549 (human alveolar adenocarcinoma), and SHSY-5Y (human neuroblastoma) cancer cell lines and the nontumorigenic HEK293 (human embryonic kidney cells) cell line. The 3,5-di-tert-butylsalicylaldehyde derived compound (8) was toxic to PC-3 human prostate adenocarcinoma cells, showing a promising IC50 value at 7.05 ± 0.76 μM. The present study also aimed to evaluate the inhibitory effects of the compounds against several key enzymes, namely carbonic anhydrase I and II (CA I and CA II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and glutathione reductase (GR), which are implicated in various global disorders, such as Alzheimer's disease, epilepsy, cancer, malaria, diabetes, and glaucoma. The inhibitory profiles of the tested compounds were assessed by determining their Ki values, which ranged from 2.96 to 9.24 nM for AChE, 3.78 to 12.57 nM for BChE, 8.42 to 25.74 nM for CA I, 7.24 to 19.74 nM for CA II, and 0.541 to 1.124 μM for GR. Molecular docking studies were also performed for all compounds. Most derivatives exhibited much more effective inhibitory action compared with clinically used standards. Thus, our findings indicate that the salicylidene derivatives presented in this study are promising drug candidates that need further evaluation.© 2023 The Authors. Archiv der Pharmazie published by Wiley-VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.