Pyrrolizinones represent an interesting class of compounds with varied degrees of structural complexity and pharmacological activity. Among these, 9H-pyrido[2,3-b]pyrrolizin-9-one, tripentone analogs, recently reported by us, showed significant antiproliferative activity against human tumor cell lines, inducing apoptosis and not affecting viability of Caco-2 differentiated in normal intestinal-like cells. Considering their interesting biological activity, their 5H-pyrido[3,2-b]pyrrolizin-5-one analogs were efficiently synthesized in good to excellent yields (61–91%). All tripentone derivatives were tested to assess their cytotoxicity against two human tumor cell lines, HCT-116 (human colorectal carcinoma) and MCF-7 (human breast cancer). The most active derivatives, with IC₅₀ ranging from 0.11 to 16.11 μM, did not affect viability of Caco-2 differentiated in normal intestinal-like cells, suggesting tumor cells as the main target of their cytotoxic action. The same compounds, further investigated, showed that they did not exert necrotic effects, while induced a clear shift of viable cells towards early apoptosis confining the cells in the mitotic phases.

吡咯烷酮代表一类有趣的化合物，具有不同程度的结构复杂性和药理活性。其中，最近由我们报道的9 H-吡啶并[2,3- b ]吡咯烷嗪9-一，曲坦酮类似物对人肿瘤细胞系表现出显着的抗增殖活性，诱导细胞凋亡且不影响Caco-2分化的Caco-2的活力。正常的肠样细胞。考虑到它们有趣的生物活性，它们的5 H-吡啶基[3,2- b有效地合成]吡咯烷酮-5-一类似物，产率高至优异（61-91％）。测试所有曲坦酮衍生物以评估其对两种人肿瘤细胞系HCT-116（人结肠直肠癌）和MCF-7（人乳腺癌）的细胞毒性。具有最强活性的衍生物（IC ₅₀为0.11至16.11μM）不影响正常肠样细胞中分化的Caco-2的活力，表明肿瘤细胞是其细胞毒性作用的主要靶标。进一步研究的相同化合物显示它们没有发挥坏死作用，同时诱导了活细胞向早期凋亡的明显转移，从而将细胞限制在有丝分裂期。