Ribeiro Joana R L, Calheiros Juliana, Silva Rita A M, Gonçalves Bruno M F, Afonso Carlos A M, Saraiva Lucília, Ferreira Maria-José U
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
LAQV/REQUIMTE-Associated Laboratory for Green Chemistry (LAQV) of the Network of Chemistry and Technology (REQUIMTE), Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, Universidade do Porto, 4050-313 Porto, Portugal.
Pharmaceuticals (Basel). 2025 May 19;18(5):750. doi: 10.3390/ph18050750.
: The search for new anticancer agents from natural sources remains a key strategy in drug discovery. This study aimed to synthesize and evaluate novel triazole derivatives of the diterpenic lactone andrographolide for their antiproliferative activity against various cancer cell lines. : Twenty-two new triazole derivatives (-), of the triacetyl derivative () of the diterpenic lactone andrographolide (), were synthesized via the azide-alkyne "click reaction". The antiproliferative effects of compounds - were evaluated using the sulforhodamine B assay against a panel of cancer cell lines and a non-tumorigenic colon cell line. A representative compound, triazole derivative , was further evaluated in human pancreatic ductal adenocarcinoma (PANC-1) cells for its effects on the cell cycle, apoptosis, migration, and drug synergy with 5-fluorouracil. : Several compounds, specifically, , , and , bearing a phenyl moiety, exhibited improved antiproliferative activity compared to the parental compound . Derivative , selected for further investigation, induced G2/M cell cycle arrest and apoptosis in a concentration-dependent manner. Additionally, this compound significantly reduced cell migration and demonstrated synergistic effects with 5-fluorouracil in PANC-1 cells. : The synthesized andrographolide-based triazole derivatives, particularly compound , showed promising antiproliferative activity and mechanisms relevant to cancer therapy. These findings support their potential as lead compounds for further development in anticancer research.
从天然来源寻找新型抗癌药物仍然是药物研发中的一项关键策略。本研究旨在合成并评估二萜内酯穿心莲内酯的新型三唑衍生物对多种癌细胞系的抗增殖活性。通过叠氮化物-炔烃“点击反应”合成了二十二种新的二萜内酯穿心莲内酯（）的三乙酰衍生物（）的三唑衍生物（-）。使用磺酰罗丹明B测定法评估化合物-对一组癌细胞系和非致瘤性结肠细胞系的抗增殖作用。在人胰腺导管腺癌（PANC-1）细胞中进一步评估代表性化合物三唑衍生物对细胞周期、凋亡、迁移的影响以及与5-氟尿嘧啶的药物协同作用。几种带有苯基部分的化合物，特别是、、和，与母体化合物相比表现出更高的抗增殖活性。被选作进一步研究的衍生物以浓度依赖的方式诱导G2/M期细胞周期阻滞和凋亡。此外，该化合物显著降低细胞迁移，并在PANC-1细胞中与5-氟尿嘧啶表现出协同作用。合成的基于穿心莲内酯的三唑衍生物，特别是化合物，显示出有前景的抗增殖活性以及与癌症治疗相关的机制。这些发现支持它们作为抗癌研究中进一步开发的先导化合物的潜力。
