Chemistry Department, Faculty of Science, Taibah University, Yanbu 46423, Saudi Arabia.
Chemistry Department, Faculty of Science, Alexandria University, P.O. Box 426 Ibrahemia, Alexandria 21321, Egypt.
Molecules. 2022 Aug 1;27(15):4912. doi: 10.3390/molecules27154912.
A variety of structurally different pyrimidines were synthesized. Elemental analysis, FT-IR, H NMR, and C NMR spectroscopy were used to confirm the chemical structures of all prepared compounds. The synthesized pyrimidines were screened against the growth of five human cancer cell lines (prostate carcinoma PC3, liver carcinoma HepG-2, human colon cancer HCT-116, human breast cancer MCF-7, human lung cancer A-549), and normal human lung fibroblasts (MRC-5) using MTT assay. Most of the screened pyrimidines have anti-proliferative activity on the growth of the PC3 cell line. Compounds and were more potent than the reference vinblastine sulfate (~2 to 3 × fold) and they can be considered promising leads for treating prostate cancer disease. Moreover, the screened compounds , , , , and were assessed according to the values of their selectivity index (SI) and were found to be more selective and safer than vinblastine sulfate. Furthermore, using in silico computational tools, the physicochemical properties of all pyrimidine ligands were assessed, and the synthesized compounds fall within the criteria of RO5, thus having the potential to be orally bioavailable.
合成了多种结构不同的嘧啶。采用元素分析、FT-IR、H NMR 和 C NMR 光谱学对所有合成化合物的化学结构进行了确认。采用 MTT 法，对合成的嘧啶进行了对五种人类癌细胞系（前列腺癌 PC3、肝癌 HepG-2、人结肠癌细胞 HCT-116、人乳腺癌 MCF-7、人肺癌 A-549）和正常人类肺成纤维细胞（MRC-5）生长的抑制活性筛选。筛选出的嘧啶类化合物对 PC3 细胞系的生长具有较强的抗增殖活性。化合物 和 比参考硫酸长春碱（约 2 至 3 倍）更有效，可被视为治疗前列腺癌疾病的有前途的先导化合物。此外，根据选择性指数（SI）的值，对筛选出的化合物 、 、 、 和 进行了评估，发现它们比硫酸长春碱更具选择性和安全性。此外，通过使用计算机模拟工具，评估了所有嘧啶配体的物理化学性质，合成的化合物符合 RO5 标准，因此具有口服生物利用度的潜力。
