Department of Therapeutic Chemistry, National Research Centre, Cairo 12622, Egypt.
Department of Microbial Chemistry, National Research Centre, Cairo 12622, Egypt.
Molecules. 2022 Jan 26;27(3):803. doi: 10.3390/molecules27030803.
The growing risk of antimicrobial resistance besides the continuous increase in the number of cancer patients represents a great threat to global health, which requires intensified efforts to discover new bioactive compounds to use as antimicrobial and anticancer agents. Thus, a new set of pyridothienopyrimidine derivatives was synthesized via cyclization reactions of 3-amino-thieno[2,3-]pyridine-2-carboxamides with different reagents. All new compounds were evaluated against five bacterial and five fungal strains. Many of the target compounds showed significant antimicrobial activity. In addition, the new derivatives were further subjected to cytotoxicity evaluation against HepG-2 and MCF-7 cancer cell lines. The most potent cytotoxic candidates (, , , , and ) were examined as EGFR kinase inhibitors. Molecular docking study was also performed to explore the binding modes of these derivatives at the active site of EGFR-PK. Compounds , and displayed broad spectrum antimicrobial activity with MIC ranges of 4-16 µg/mL and potent cytotoxic activity with IC ranges of 1.17-2.79 µM. In addition, they provided suppressing activity against EGFR with IC ranges of 7.27-17.29 nM, higher than that of erlotinib, IC = 27.01 nM.
除了癌症患者数量的持续增加外，抗菌药物耐药性的不断增加也对全球健康构成了巨大威胁，这需要加强努力来发现新的生物活性化合物，用作抗菌和抗癌药物。因此，通过 3-氨基噻吩并[2,3-d]嘧啶-2-甲酰胺与不同试剂的环化反应，合成了一组新的吡啶并噻吩嘧啶衍生物。所有新化合物都针对五种细菌和五种真菌菌株进行了评估。许多目标化合物表现出显著的抗菌活性。此外，还进一步对新衍生物进行了对 HepG-2 和 MCF-7 癌细胞系的细胞毒性评估。对最有效的细胞毒性候选物（、、、、和）进行了作为 EGFR 激酶抑制剂的检测。还进行了分子对接研究，以探索这些衍生物在 EGFR-PK 活性部位的结合模式。化合物、和表现出广谱抗菌活性，MIC 范围为 4-16 µg/mL，具有很强的细胞毒性，IC 范围为 1.17-2.79 µM。此外，它们对 EGFR 的抑制活性为 7.27-17.29 nM，高于厄洛替尼（IC=27.01 nM）。
