Abu-Hashem Ameen Ali, Hakami Othman, Amri Nasser
Department of Physical Sciences, Chemistry Division, College of Science, Jazan University, P.O. Box. 114, Jazan 45142, Kingdom of Saudi Arabia.
Heliyon. 2024 Feb 29;10(5):e26735. doi: 10.1016/j.heliyon.2024.e26735. eCollection 2024 Mar 15.
Recently, heterocyclic compounds such as pyrido [2,3-] pyrimidinones, 1,2,4-triazolopyrimidines, pyrimidoquinazolines, and quinoline derivatives have gained attention from researchers due to their pharmacological and biological activities. To synthesize new compounds, quinoline-2-thioxopyrido [2,3-] pyrimidinone and methylthioquinoline-pyrido [2,3-] pyrimidinones were used as starting materials. The new compounds synthesized were quinoline-pyrido [2,3-] (DeGoey et al., 2013; Gouda et al., 2020; Dangolani et al., 2018) [1, 2,4]triazolopyrimidinones , 2-methylsulfonyl-quinoline-pyrido [2,3-]pyrimidinone , pyrido [2,3-]pyrimidine derivatives, pyridopyrimido (Gouda et al., 2020; DeGoey et al., 2013) 2,12,1-b] quinazoline , pyrido [(Khajouei et al., 2021; Gouda et al., 2020) 3,23,2-e]bis (1,2,4-triazole)pyrimidine and pyridopyrimido-diquinazoline-dione derivatives. These compounds were synthesized with high efficiency, producing yields ranging from 69% to 90%, under moderate conditions, through treating or with various reagents such as anthranilic acid, phosphorus oxychloride, hydrazine hydrate, formic acid, glacial acetic acid, arylamine (aniline, 4-chloroaniline, or 4-methoxyaniline), and sec-amine (piperazine or morpholine). The new structures of the synthesized compounds were verified using various spectroscopic procedures, such as IR, NMR, and mass spectra. Molecular docking studies were carried out to investigate and discuss how the prepared compounds bind to amino acids such as Estrogen Receptor alpha, EGFR, and NADPH oxidase protein. Also, the synthesized products were tested for their anticancer and antioxidant activities against the (MCF-7) breast carcinoma cell line and human normal Retina pigmented epithelium cells (RPE-1). The study on the structure-activity relationship (SAR) established a correlation between the chemical structure of the newly synthesized compounds and their anticancer activity. The findings suggest that compounds , ,, and exhibited promising anticancer activity and antioxidant effects as measured by DPPH inhibition.
最近，吡啶并[2,3 - ]嘧啶酮、1,2,4 - 三唑并嘧啶、嘧啶并喹唑啉和喹啉衍生物等杂环化合物因其药理和生物活性而受到研究人员的关注。为了合成新化合物，以喹啉 - 2 - 硫代吡啶并[2,3 - ]嘧啶酮和甲硫基喹啉 - 吡啶并[2,3 - ]嘧啶酮作为起始原料。合成的新化合物有喹啉 - 吡啶并[2,3 - ][1,2,4]三唑并嘧啶酮（DeGoey等人，2013年；Gouda等人，2020年；Dangolani等人，2018年）、2 - 甲基磺酰基 - 喹啉 - 吡啶并[2,3 - ]嘧啶酮、吡啶并[2,3 - ]嘧啶衍生物、吡啶并嘧啶并[2,1 - b]喹唑啉（Gouda等人，2020年；DeGoey等人，2013年）、吡啶并[(Khajouei等人，2021年；Gouda等人，2020年)3,2 - e]双(1,2,4 - 三唑)嘧啶和吡啶并嘧啶并二喹唑啉二酮衍生物。这些化合物在温和条件下通过用各种试剂（如邻氨基苯甲酸、三氯氧磷、水合肼、甲酸、冰醋酸、芳胺（苯胺、4 - 氯苯胺或4 - 甲氧基苯胺）和仲胺（哌嗪或吗啉））处理或 高效合成，产率范围为69%至90%。使用各种光谱学方法（如红外光谱、核磁共振光谱和质谱）验证了合成化合物的新结构。进行了分子对接研究，以调查和讨论所制备的化合物如何与雌激素受体α、表皮生长因子受体和NADPH氧化酶蛋白等氨基酸结合。此外，测试了合成产物对（MCF - 7）乳腺癌细胞系和人正常视网膜色素上皮细胞（RPE - 1）的抗癌和抗氧化活性。对构效关系（SAR）的研究建立了新合成化合物的化学结构与其抗癌活性之间的相关性。研究结果表明，化合物 、 、 和 通过DPPH抑制测定显示出有前景的抗癌活性和抗氧化作用。
