ABSTRACT
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 AlCl3 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 (IC50 = 3.60 and 4.40 µM, respectively), and in general, the non-halogenated compounds were better inhibitors of AChE and BChE than the halogenated molecules. However, the inhibitory potency of compounds 3a-n was weaker than that of tacrine. By molecular docking simulations, it was found that the size of the spirocarbocyclic moieties is inversely proportional to the inhibitory activity of the cholinesterases, probably because an increase in the size of the spirocyclic component sterically hindered the interaction of tacrine derivatives with the active site of tested cholinesterases. The findings obtained here may help in the design and development of new anticholinesterase drugs.
Subject(s)
Cholinesterase Inhibitors/pharmacology , Cholinesterases/metabolism , Cycloparaffins/pharmacology , Quinolines/pharmacology , Animals , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/chemistry , Cycloparaffins/chemical synthesis , Cycloparaffins/chemistry , Dose-Response Relationship, Drug , Electrophorus , Horses , Molecular Docking Simulation , Molecular Structure , Quinolines/chemical synthesis , Quinolines/chemistry , Structure-Activity RelationshipABSTRACT
This article presents the statistical analysis data from Drosophila melanogaster development (from larvae to adult) and learning and memory retention behavior of a Pavlovian conditioning in male and female flies exposed to copper. While the full data sets are available In the article: Copper decrease associative learning and memory in D. melanogaster, this data-in-brief article includes the detailed statistical analysis performed. Data demonstrates Statistica Software analysis between the subject part of the analysis: 2 treatments x 2 sexes x 2 ages and within subject part of the analysis: 2 treatments x 2 sex x 2 ages x 4 times, repeated measures.