Laboratório de Química Farmacêutica, Faculdade de Farmácia da Universidade de Coimbra, Poló das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
Bioorg Med Chem. 2012 Oct 1;20(19):5774-86. doi: 10.1016/j.bmc.2012.08.010. Epub 2012 Aug 16.
A series of new heterocyclic derivatives of ursolic acid 1 were synthesized and evaluated for their antiproliferative activity against AsPC-1 pancreatic cancer cells. Compounds 24-32, with an α,β unsaturated ketone in conjugation with an heterocyclic ring in ring A have improved antiproliferative activities. Compound 32 is the most active compound with an IC(50) of 1.9 μM which is sevenfold more active than ursolic acid 1. Compound 32 arrests cell cycle in G1 phase and induces apoptosis in AsPC-1 cells with upregulation of p53, p21(waf1) and NOXA protein levels.
一系列新型熊果酸的杂环衍生物 1 被合成，并评估其对 AsPC-1 胰腺癌细胞的抗增殖活性。化合物 24-32，在 A 环中具有共轭的α,β 不饱和酮和杂环，具有改善的抗增殖活性。化合物 32 是最活性的化合物，IC(50)为 1.9 μM，比熊果酸 1 活性高七倍。化合物 32 将细胞周期阻滞在 G1 期，并诱导 AsPC-1 细胞凋亡，同时上调 p53、p21(waf1)和 NOXA 蛋白水平。
