Spallarossa Andrea, Caneva Chiara, Caviglia Matteo, Alfei Silvana, Butini Stefania, Campiani Giuseppe, Gemma Sandra, Brindisi Margherita, Zisterer Daniela M, Bright Sandra A, Williams Clive D, Crespan Emmanuele, Maga Giovanni, Sanna Giuseppina, Delogu Ilenia, Collu Gabriella, Loddo Roberta
Dipartimento di Farmacia, Università di Genova, Viale Benedetto XV 3, I-16132 Genova, Italy.
Dipartimento di Farmacia, Università di Genova, Viale Benedetto XV 3, I-16132 Genova, Italy.
Eur J Med Chem. 2015 Sep 18;102:648-60. doi: 10.1016/j.ejmech.2015.08.009. Epub 2015 Aug 8.
A new series of indole-based analogues were recently identified as potential anticancer agents. The Knoevenagel-type indoles herein presented were prepared via a one-pot condensation of iminium salts with active methylene reagents and were isolated as single geometric isomers. Biological evaluation in different cell-based assays revealed an antiproliferative activity for some analogues already in the nanomolar range against leukaemia, breast and renal cancer cell lines. To explain these effects, the most promising analogues of the series were engaged in further cell-based studies. Compounds 5e, l, p and 6a, b highlighted a pro-apoptotic potential being able to induce apoptosis in HL60, K562 and MCF-7 cell lines in a dose and time-dependent manner. The ability of these compounds to arrest cell cycle at the G2/M phase inspired the immunofluorescence studies which allowed us to identify tubulin as a potential target for compounds 5l and 6b.
最近，一系列新型吲哚类类似物被鉴定为潜在的抗癌药物。本文介绍的克诺文纳格尔型吲哚是通过亚胺盐与活性亚甲基试剂的一锅法缩合制备的，并以单一几何异构体形式分离出来。在不同的基于细胞的实验中的生物学评估显示，一些类似物对白血病、乳腺癌和肾癌细胞系已经具有纳摩尔范围内的抗增殖活性。为了解释这些作用，该系列中最有前景的类似物被用于进一步的基于细胞的研究。化合物5e、l、p和6a、b突出显示了促凋亡潜力，能够以剂量和时间依赖性方式在HL60、K562和MCF-7细胞系中诱导凋亡。这些化合物在G2/M期使细胞周期停滞的能力激发了免疫荧光研究，使我们能够确定微管蛋白是化合物5l和6b的潜在靶点。
