PMID- 23931443
OWN - NLM
STAT- MEDLINE
DCOM- 20140310
LR  - 20190907
IS  - 1873-4294 (Electronic)
IS  - 1568-0266 (Linking)
VI  - 13
IP  - 15
DP  - 2013
TI  - Multifunctional tacrine derivatives in Alzheimer's disease.
PG  - 1771-86
AB  - Tacrine (1) was the first acetylcholinesterase inhibitor (AChEI) introduced in 
      therapy for the treatment of Alzheimer's disease (AD), but similarly to the most 
      recent approved AChEIs and memantine, an N-methyl-D-aspartate receptor (NMDAR) 
      antagonist, it does not represent an effective drug in halting the progression of 
      AD. The continuous research in this field has contributed to delineate AD as a 
      multifactorial syndrome with several biological targets involved in its etiology. 
      On these bases, the development of new effective therapeutics becomes crucial and 
      the design of molecules that address more than one specific AD target should 
      represent thus a succeeded strategy for AD treatment. This review will focus on 
      and summarize multifunctional 1 derivatives starting from our last paper 
      published on the same topic in 2010. In the last three years, the design and 
      synthesis of 1 homo- and heterodimers, as well as of 1-hybrid structures for AD 
      therapy, was aimed mainly to discover safer drugs, with decreased hepatotoxicity 
      in comparison to 1, taking also into account the multifactorial pathogenesis of 
      the disease. Most of these new hetero/homo-dimers and/or hybrids of 1, although 
      addressed mainly to acetylcholinesterase (AChE) and Abeta aggregation inhibition, 
      are able to hit additional targets relevant to AD, among which, beta-secretase 
      (BACE1), reactive oxygen species (ROS), calcium channels, NMDAR and M1- 
      muscarinic receptors.
FAU - Minarini, Anna
AU  - Minarini A
AD  - Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of 
      Bologna, Via Belmeloro 6, 40126 Bologna, Italy. anna.minarini@unibo.it
FAU - Milelli, Andrea
AU  - Milelli A
FAU - Simoni, Elena
AU  - Simoni E
FAU - Rosini, Michela
AU  - Rosini M
FAU - Bolognesi, Maria Laura
AU  - Bolognesi ML
FAU - Marchetti, Chiara
AU  - Marchetti C
FAU - Tumiatti, Vincenzo
AU  - Tumiatti V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United Arab Emirates
TA  - Curr Top Med Chem
JT  - Current topics in medicinal chemistry
JID - 101119673
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nootropic Agents)
RN  - 0 (Receptor, Muscarinic M1)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 4VX7YNB537 (Tacrine)
RN  - EC 3.1.1.8 (Cholinesterases)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
SB  - IM
MH  - Alzheimer Disease/*drug therapy/metabolism/physiopathology
MH  - Amyloid Precursor Protein Secretases/antagonists & inhibitors/metabolism
MH  - Amyloid beta-Peptides/antagonists & inhibitors/chemistry/metabolism
MH  - Calcium Channel Blockers/*chemical synthesis/therapeutic use
MH  - Calcium Channels/metabolism
MH  - Cholinesterases/metabolism
MH  - *Drug Design
MH  - Enzyme Inhibitors/*chemical synthesis/therapeutic use
MH  - Humans
MH  - Nootropic Agents/*chemical synthesis/therapeutic use
MH  - Receptor, Muscarinic M1/antagonists & inhibitors/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism
MH  - Tacrine/analogs & derivatives/*chemical synthesis/therapeutic use
EDAT- 2013/08/13 06:00
MHDA- 2014/03/13 06:00
CRDT- 2013/08/13 06:00
PHST- 2013/03/12 00:00 [received]
PHST- 2013/04/29 00:00 [accepted]
PHST- 2013/08/13 06:00 [entrez]
PHST- 2013/08/13 06:00 [pubmed]
PHST- 2014/03/13 06:00 [medline]
AID - CTMC-EPUB-54919 [pii]
AID - 10.2174/15680266113139990136 [doi]
PST - ppublish
SO  - Curr Top Med Chem. 2013;13(15):1771-86. doi: 10.2174/15680266113139990136.