3-氰基吡啶衍生物因其强大的抑制各种生物靶标（包括 Pim-1 激酶、生存素和微管蛋白聚合）的能力而表现出优异的抗癌活性。另一方面，N-酰基腙（NAH）被认为是药物化学和药物设计中非常通用的基序。基于这些数据，我们在本文中报告了新型 3-氰基吡啶结合 N-酰基肼支架的合成，评估了它们对乳腺癌 (MCF-7) 和卵巢 (A-2780) 癌细胞系的细胞毒性及其作用抗氧化特性。除4a和4d外，所有测试分子均对A-2780表现出高细胞毒性，IC50值范围为1.14至1.76μM。相反，只有四种分子3d、4b、4c和4d表现出针对MCF-7的细胞毒性，IC50值范围为1.14至3.38μM。另一方面，所有测试的分子在 DPPH 和金属螯合测定中都表现出中等的抗氧化能力。对接和分子动力学研究表明，2d、3d 和 4d 是微管蛋白和雌激素受体的潜在抑制剂，这可能解释了它们的高细胞毒性。这些结果有望深入研究这些新合成的 3-氰基吡啶-N-酰腙，将其用作潜在的抗癌候选药物。© 2024 Wiley periodicals LLC。

3-Cyanopyridine derivatives are known for exhibiting excellent anticancer activity due to their strong capability to inhibit various biological targets, including Pim-1 kinase, survivin, and tubulin polymerization. On the other hand, N-acylhydrazones (NAH) are known to be a very versatile motif in medicinal chemistry and drug design. Based on these data, we report in this paper, the synthesis of novel 3-cyanopyridines incorporating N-acyl hydrazine scaffold, the evaluation of their cytotoxicity on the breast (MCF-7) and ovarian (A-2780) cancer cell lines and their antioxidant properties. Excluding 4a and 4d, all tested molecules exhibited high cytotoxicity against A-2780, with IC50 values ranging from 1.14 to 1.76 µM. Conversely, only four molecules 3d, 4b, 4c, and 4d demonstrated cytotoxicity against MCF-7, with IC50 values ranging from 1.14 to 3.38 µM. On the other hand, all the tested molecules exhibited a moderate antioxidant capacity in both the DPPH and metal chelation assays. Docking and molecular dynamics studies revealed that 2d, 3d, and 4d are potential inhibitors of tubulin and the œstrogen receptor, which may explain their high cytotoxicity. These results are promising to study these newly synthesized 3-cyanopyridine-N-acylhydrazones in depth for use as potential anticancer candidates.© 2024 Wiley Periodicals LLC.