7-Amine-spiro[chromeno[4,3-b]quinoline-6,1'-cycloalkanes]: Synthesis and cholinesterase inhibitory activity of structurally modified tacrines.

Five new examples of 9,10-chloro(bromo)-7-amine-spiro[chromeno[4,3-b]quinoline-6,1'-cycloalkanes] - in which cycloalkanes = cyclopentane, cyclohexane, and cycloheptane - were synthesized at yields of 42-56%, using a sequential one-pot two-step cyclocondensation reaction of three different scaffolds of 2-aminobenzonitriles and the respective spiro[chroman-2,1'-cycloalkan]-4-ones, and using AlCl as the catalyst in a solvent-free method. Subsequently, the five new spirochromeno-quinolines and nine quinolines previously published by us (14 modified tacrine scaffolds) were subjected to AChE and BChE inhibitory activity evaluation. The molecule containing a spirocyclopentane derivative had the highest AChE and BChE inhibitory activity (IC = 3.

Tacrine derivatives stimulate human glioma SF295 cell death and alter important proteins related to disease development: An old drug for new targets.

Glioblastoma is the most common and aggressive glioma, characterized by brain invasion capability. Being very resistant to the current therapies, since even under treatment, surgery, and chemotherapy with temozolomide (TMZ), patients achieve a median survival of one year. In the search for more effective therapies, new molecules have been designed.