title: Purine homo-N-nucleoside+coumarin hybrids as pleiotropic agents for the potential treatment of Alzheimer's disease.
abstract: OBJECTIVE
  Due to the complex nature of Alzheimer's disease, there is a renewed search for pleiotropic agents.
  
  
  RESULTS
  Purine+coumarin hybrids have been synthesized and tested for the potential treatment of Alzheimer's disease. Hybrids 6, 4a-b, 14c and 14e inhibit significantly soybean lipoxygenase, whereas derivatives 14b, c and 20a present antioxidative/lipoxygenase inhibition activities. Cholinesterase (ChE) and monoamino oxidase (MAO) inhibition studies have been carried out. Hybrid 20a is the most potent ChE inhibitor, in the low micromolar range, and selective for hBuChE (IC50 = 4.65 ± 0.23 μM), whereas hybrid 14a is the most potent MAOI, in the low micromolar range, and selective for MAO-B (IC50 = 6.8 ± 0.6 μM).
  
  
  CONCLUSIONS
  The preliminary experimental results point to two selective multitarget lead compounds 20a and 4b.
authors: Laboratory of Organic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors: Michael G
authors: MG
authors: Kallitsakis
authors: Matilde
authors: M
authors: Yañez
authors: Elena
authors: E
authors: Soriano
authors: José
authors: J
authors: Marco-Contelles
authors: Dimitra J
authors: DJ
authors: Hadjipavlou-Litina
authors: Konstantinos E
authors: KE
authors: Litinas
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D003374:Coumarins / Q000737:chemistry*; D006801:Humans; D000960:Hypolipidemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry; D011687:Purines / Q000737:chemistry*; D013025:Glycine max / Q000201:enzymology; D013329:Structure-Activity Relationship
chemical_list: D003374:Coumarins; D000960:Hypolipidemic Agents; D016859:Lipoxygenase Inhibitors; D009705:Nucleosides; D011687:Purines; C030123:coumarin; D008084:Lipoxygenase; C030985:purine