Unconventional Knoevenagel-type indoles: Synthesis and cell-based studies for the identification of pro-apoptotic agents

作者：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

来源：European Journal of Medicinal Chemistry, 2015, 102: 648-660.

DOI：10.1016/j.ejmech.2015.08.009

• Indoles
• Antiproliferative agents
• Pro-apoptotic agents
• Tubulin immunostaining

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, I, 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.

• 出版日期2015-9-18