Abstract

New strategy for the synthesis of 2-(2,3,6,9-tetrahydro-1,3-dimethyl-2,6-dioxo-1H-purin-8-yl)acetonitrile through a molecular linking with pyridopyrimidine, pyrazolopyridine, and pyranonapthyridine derivatives. The newly synthesized compounds were characterized on the basis of spectral (FT-IR, ¹H, ¹³C NMR, Mass spectral) analyses and further screened for their antimicrobial, antioxidant, and anticancer properties. Compound 6a indicated a higher activity against Gram-negative bacteria and compound 7d toward Gram-positive bacteria. Antifungal validation of the compounds revealed 7b as sensible against Aspergillus niger, Aspergillus oryzae, Candida albicans, and Penicillium chrysogenum at all concentrations. Compound 6b showed prominent cytotoxic activity with IC₅₀ (µM) values of 0.8 ± 0.61, 1.0 ± 0.3, 1.2 ± 0.7, and 0.90 ± 0.71 against MCF-7, A-549, HeLa, and Panc-1 cancer cell lines, respectively. Compounds 6c and 10c showed significant antioxidant activity at all concentrations with ED₅₀ values (3.39 ± 0.3 and 4.27 ± 0.5 μM, respectively). Further, docking was performed at the 1SA5 active site to anticipate their conceivable binding mode by compound 6b.

摘要

通过与吡啶并嘧啶、吡唑并吡啶的分子连接合成2-(2,3,6,9-tetrahydro-1,3-dimethyl-2,6-dioxo-1 H -purin -8-yl)乙腈的新策略，和吡喃萘啶衍生物。^{在光谱（FT-IR、 1} H、¹³ C NMR、质谱）分析的基础上对新合成的化合物进行了表征，并进一步筛选了它们的抗菌、抗氧化和抗癌特性。化合物6a对革兰氏阴性菌有较高的活性，化合物7d对革兰氏阳性菌有较高的活性。化合物的抗真菌验证表明7b对黑曲霉、米曲霉敏感、白色念珠菌和所有浓度的产黄青霉。化合物6b显示出显着的细胞毒活性，对 MCF-7、A-549、HeLa 和 Panc-1 癌细胞系的IC ₅₀ (µM) 值分别为 0.8 ± 0.61、1.0 ± 0.3、1.2 ± 0.7 和 0.90 ± 0.71 . 化合物6c和10c在所有浓度下均显示出显着的抗氧化活性，ED ₅₀值（分别为 3.39 ± 0.3 和 4.27 ± 0.5 μM）。此外，在 1SA5 活性位点进行对接，以预测化合物6b可能的结合模式。