PMID- 19689389
OWN - NLM
STAT- MEDLINE
DCOM- 20091221
LR  - 20191210
IS  - 1875-6638 (Electronic)
IS  - 1573-4064 (Linking)
VI  - 5
IP  - 4
DP  - 2009 Jul
TI  - The structure-AChE inhibitory activity relationships study in a series of 
      pyridazine analogues.
PG  - 325-35
AB  - The structure-activity relationships (SAR) are investigated by means of the 
      Electronic-Topological Method (ETM) followed by the Neural Networks application 
      (ETM-NN) for a class of anti-cholinesterase inhibitors (AChE, 53 molecules) being 
      pyridazine derivatives. AChE activities of the series were measured in IC(50) 
      units, and relative to the activity levels, the series was partitioned into 
      classes of active and inactive compounds. Based on pharmacophores and 
      antipharmacophores calculated by the ETM-software as sub-matrices containing 
      important spatial and electronic characteristics, a system for the activity 
      prognostication is developed. Input data for the ETM were taken as the results of 
      conformational and quantum-mechanics calculations. To predict the activity, we 
      used one of the most well known neural networks, namely, the feed-forward neural 
      networks (FFNNs) trained with the back propagation algorithm. The supervised 
      learning was performed using a variant of FFNN known as the Associative Neural 
      Networks (ASNN). The result of the testing revealed that the high ETM's ability 
      of predicting both activity and inactivity of potential AChE inhibitors. Analysis 
      of HOMOs for the compounds containing Ph1 and APh1 has shown that atoms with the 
      highest values of the atomic orbital coefficients are mainly those atoms that 
      enter into the pharmacophores. Thus, the set of pharmacophores and 
      antipharmacophores found as the result of this study forms a basis for a system 
      of the anti-cholinesterase activity prediction.
FAU - Saracoglu, M
AU  - Saracoglu M
AD  - Faculty of Education, Erciyes University, 38039, Kayseri, Turkey. 
      muratsaracoglu@gmail.com
FAU - Kandemirli, F
AU  - Kandemirli F
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Med Chem
JT  - Medicinal chemistry (Shariqah (United Arab Emirates))
JID - 101240303
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Pyridazines)
RN  - 449GLA0653 (pyridazine)
RN  - EC 3.1.1.8 (Cholinesterases)
SB  - IM
MH  - Algorithms
MH  - Animals
MH  - Cholinesterase Inhibitors/*chemistry/*pharmacology
MH  - Cholinesterases/chemistry/*metabolism
MH  - Drug Discovery
MH  - Electrons
MH  - Electrophorus
MH  - Models, Molecular
MH  - Molecular Conformation
MH  - Neural Networks, Computer
MH  - Pyridazines/*chemistry/*pharmacology
MH  - Quantum Theory
MH  - Structure-Activity Relationship
EDAT- 2009/08/20 09:00
MHDA- 2009/12/22 06:00
CRDT- 2009/08/20 09:00
PHST- 2009/08/20 09:00 [entrez]
PHST- 2009/08/20 09:00 [pubmed]
PHST- 2009/12/22 06:00 [medline]
AID - 10.2174/157340609788681511 [doi]
PST - ppublish
SO  - Med Chem. 2009 Jul;5(4):325-35. doi: 10.2174/157340609788681511.