在全球范围内，癌症是最常见的慢性疾病相关死亡原因。虽然抗癌药物有很多种，但有些药物却有不良反应。由于副作用有限，天然产物比合成药物更受青睐。穿心莲内酯及其衍生物已知是有效的抗癌剂。在这种情况下，来自3-芳基-1-H-吡唑-4-醛的十六种新型穿心莲内酯和异穿心莲内酯(1a-1h、2a-2g、2i)的3,19-(NH-3-芳基-吡唑)缩醛( a-i) 被合成。所有合成的化合物均使用 1H NMR、13C NMR、HRMS、FT-IR 和 UV-vis 光谱进行表征。美国 NCI 对所有化合物的抗癌潜力进行了针对 60 种不同人类癌细胞系的评估。选择对所有 60 细胞系具有良好 GI50（50% 生长抑制活性）的四种化合物进行进一步的体外研究。在这四种化合物中，化合物 1g 对结肠癌细胞系 HCT-116 表现出最佳的 IC50 (3.08 μM)。细胞周期分析、膜联蛋白V-FITC/PI和ROS测定表明，化合物1g诱导的HCT-116细胞凋亡主要归因于细胞内ROS水平升高。此外，构效关系表明穿心莲内酯的吡唑部分在其抗癌特性中发挥着关键作用。对这些化合物进行了进一步的计算机 ADMET 和 Lipinski 特性检查，以评估它们作为先导化合物的潜力。该期刊版权所有 © 英国皇家化学学会。

Globally, cancer is the most prevalent chronic disease-related cause of death. Although there are many anticancer drugs, some of them have adverse effects. Due to their limited side effects, natural products are preferred over synthetic drugs. Andrographolide and its derivatives are known to be potent anticancer agents. In this context, sixteen novel 3,19-(NH-3-aryl-pyrazole) acetals of andrographolide and isoandrographolide (1a-1h, 2a-2g, 2i) from 3-aryl-1-H-pyrazole-4-carboxaldehydes (a-i) were synthesized. All the synthesized compounds were characterized using 1H NMR, 13C NMR, HRMS, FT-IR, and UV-vis spectroscopy. All the compounds were evaluated against a panel of 60 different human cancer cell lines for their anticancer potential at NCI, USA. Four compounds, having promising GI50s (50% growth inhibitory activity) on all 60-cell lines were selected for further in vitro studies. Out of these four compounds, compound 1g exhibited the best IC50 (3.08 μM) against the colon cancer cell line, HCT-116. Cell cycle analysis, annexin V-FITC/PI, and ROS assays revealed that the apoptosis of HCT-116 cells induced by compound 1g could be mainly attributed to the elevated levels of intracellular ROS. Further, the structure-activity relationship revealed that the pyrazole moiety of andrographolide plays a key role in their anticancer properties. These compounds were further examined for in silico ADMET and Lipinski characteristics to assess their potential as lead compounds.This journal is © The Royal Society of Chemistry.