Repurposing N,N'-bis-(arylamidino)-1,4-piperazinedicarboxamidines: An unexpected class of potent inhibitors of cholinesterases.
Drug repurposing (=drug repositioning) is an effective way to cut costs for the development of new therapeutics and to reduce the time-to-market time-span. Following this concept a small library of compounds was screened for their ability to act as inhibitors of acetyl- and butyrylcholinesterase. Picloxydine, an established antiseptic, was shown to be an inhibitor for both enzymes. Systematic variation of the aryl substituents led to analogs possessing almost the same good properties as gold standard galantamine hydrobromide.
Martin-Luther University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
Anne
A
Loesche
Martin-Luther University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
Jana
J
Wiese
Martin-Luther University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
Sven
S
Sommerwerk
Martin-Luther University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
Vivienne
V
Simon
Leibniz Institute of Plant Biochemistry, Bioorganic Chemistry, Weinberg 3, 06120 Halle (Saale), Germany.
Wolfgang
W
Brandt
Martin-Luther University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany. Electronic address: rene.csuk@chemie.uni-halle.de.
René
R
Csuk
D000110:Acetylcholinesterase / Q000378:metabolism; D000891:Anti-Infective Agents, Local / Q000737:chemistry* / Q000494:pharmacology*; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D058492:Drug Repositioning; D006801:Humans; D062105:Molecular Docking Simulation; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology*
D000891:Anti-Infective Agents, Local; D002800:Cholinesterase Inhibitors; D010879:Piperazines; C005253:picloxydine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
Acetylcholinesterase; Bisbiguanides; Butyrylcholinesterase; Picloxydine