Background: The continuous need for new anticancer drugs is never-ending task due to cancer resistance to the existing drugs.

Objective: This article aimed to design, synthesis, characterization, and anticancer evaluation of cyanopyridines, pyridopyrazolopyrimidines and pyridopyrazolotriazines.

Methods: Anticancer activity of the synthesized compounds was determined using MTT assay against three cancer cell lines, namely liver cancer cell line (HepG-2), pancreatic cancer cell line (PANC-1), non-small lung cancer cell line (A-549) and normal fibroblast.

Results and Discussion: A series of 3-cyanopyridines (2a,b, 4, 5, 9), pyridopyrimidine (10), pyridopyrazolopyrimidines (11a-c, 12a,b, 18), pyrazolopyridine salt (13) and pyridopyrazolotriazines (16a,b) were synthesized from 3-cyano-4,6-dimethyl-2-pyridone. The synthesized compounds were evaluated in vitro for their anticancer activity and their chemical structures were determined by elemental analysis and spectroscopic data.

Conclusion: Some of the synthesized compounds showed remarkable anticancer activities, especially 11a exhibited superior potency to the reference drug cisplatin against A-549 (IC50 = 9.24 μg mL-1 compared to 11.76 μg mL-1 for reference drug) and was found to be safe (IC50 = 66 μg mL-1) for normal fibroblast. Furthermore, compound 16a displayed the highest activity among the tested compounds against HepG-2 (IC50 = 6.45 μg mL-1 equipotent to cisplatin) with the highest safety profile for normal fibroblast (IC50=113.97 μg mL-1).

背景：由于癌症对现有药物的耐药性，对新抗癌药物的持续需求是永无止境的任务。

目的：本文旨在设计、合成、表征和抗癌评价氰基吡啶、吡啶并吡唑并嘧啶和吡啶并吡唑并三嗪。

方法：采用MTT法测定合成化合物对三种癌细胞系的抗癌活性，即肝癌细胞系（HepG-2）、胰腺癌细胞系（PANC-1）、非小肺癌细胞系（A- 549) 和正常的成纤维细胞。

结果与讨论：一系列 3-氰基吡啶（2a、b、4、5、9）、吡啶并嘧啶（10）、吡啶并吡唑并嘧啶（11a-c、12a、b、18）、吡唑并吡啶盐（13）和吡啶并吡唑并三嗪（16a， b) 由 3-氰基-4,6-二甲基-2-吡啶酮合成。合成的化合物在体外评估了它们的抗癌活性，并通过元素分析和光谱数据确定了它们的化学结构。

结论：一些合成的化合物显示出显着的抗癌活性，尤其是 11a 对 A-549 表现出优于参考药物顺铂的效力（IC50 = 9.24 μg mL-1，而参考药物为 11.76 μg mL-1），并且发现对正常成纤维细胞是安全的 (IC50 = 66 μg mL-1)。此外，化合物 16a 在测试化合物中对 HepG-2 的活性最高（IC50 = 6.45 μg mL-1 与顺铂等效），对正常成纤维细胞的安全性最高（IC50 = 113.97 μg mL-1）。