title: Advanced Structure-activity Relationships Applied to Mentha spicata L. Subsp. spicata Essential Oil Compounds as AChE and NMDA Ligands, in Comparison with Donepezil, Galantamine and Memantine - New Approach in Brain Disorders Pharmacology.
abstract: BACKGROUND
  Alzheimer's disease (AD) therapy is based on several natural and synthetic compounds that act as acetylcholinesterase (AChE) and N-methyl-D-aspartate receptor (NMDA) ligands that have limited efficiency in relieving AD symptoms. Recent studies show that inhibitors isolated from Mentha spicata L. subsp. spicata are promising for AD therapy.
  
  
  OBJECTIVE
  We aimed to identify novel and more potent phytopharmaceutical compounds for AD treatment by taking into account the compounds from Mentha spicata L. subsp. spicata essential oil.
  
  
  METHODS
  We generated structure-activity relationship (SAR) models that predict the biological activities of 14 Mentha spicata L. subsp. spicata compounds on AChE and NMDA by comparing their molecular features with those of the three conventional ligands: donepezil, galantamine and memantine.
  
  
  RESULTS
  The most relevant descriptors for predicting the biological activities of considered compounds are solvent accessible area and their subdivided, hydrophobicity, energy of frontier molecular orbitals and counts of the aromatic ring and rotatable bounds. 1,8-cineole, the main compound from Mentha spicata L. subsp. spicata essential oil, resulted to be similar with memantine and dissimilar with donepezil in respect to hidrophobicity (logP1,8-cineole=2.95, logPmemantine=2.81, logPdonepezil=4.11), the energy of LUMO (eLUMO1,8-cineole=3.01 eV, eLUMOmemantine=3.35 eV, eLUMOdonepezil=-0.35 eV) and the solvent accessible surface areas over all hydrophobic (SA_H1,8-cineole= 350 Å2, SA_Hmemantine= 358 Å2, SA_Hdonepezil= 655 Å2) or polar atoms (SA_P1,8-cineole= 4 Å2, SA_Pmemantine=10 Å2, SA_Pdonepezil=44.62 Å2).
  
  
  CONCLUSIONS
  Our results point towards 1,8-cineole as a good candidate for NMDA antagonism, with a weaker AChE inhibitory effect. Our results may be useful in establishing new therapeutic strategies for neurological disorders.
authors.affiliation: Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Bucharest. Romania.
authors.forename: Speranta
authors.initials: S
authors.lastname: Avram
authors.affiliation: Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 91-95th Spl. Independentei: 050095, Bucharest. Romania.
authors.forename: Maria
authors.initials: M
authors.lastname: Mernea
authors.affiliation: Department of Biology, Faculty of Science, Firat University, Elazig. Turkey.
authors.forename: Eyup
authors.initials: E
authors.lastname: Bagci
authors.affiliation: Department of Biology, "Alexandru Ioan Cuza" University of Iasi, Iasi. Romania.
authors.forename: Lucian
authors.initials: L
authors.lastname: Hritcu
authors.affiliation: Department of Occupational Health, Faculty of Medicine, "Victor Babes" University of Medicine and Pharmacy Timisoara, Timisoara. Romania.
authors.forename: Livia-Cristina
authors.initials: LC
authors.lastname: Borcan
authors.affiliation: Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Bucharest. Romania.
authors.forename: Dan Florin
authors.initials: DF
authors.lastname: Mihailescu
mesh_terms: D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D003511:Cyclohexanols / Q000737:chemistry* / Q000494:pharmacology; D000077265:Donepezil; D000077591:Eucalyptol; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000494:pharmacology*; D005702:Galantamine / Q000737:chemistry* / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D007189:Indans / Q000737:chemistry* / Q000494:pharmacology; D008559:Memantine / Q000737:chemistry* / Q000494:pharmacology; D031337:Mentha spicata / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D039821:Monoterpenes / Q000737:chemistry* / Q000494:pharmacology; D009822:Oils, Volatile / Q000737:chemistry / Q000494:pharmacology*; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D003511:Cyclohexanols; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D039821:Monoterpenes; D009822:Oils, Volatile; D010880:Piperidines; D005702:Galantamine; D000077265:Donepezil; D000077591:Eucalyptol; D008559:Memantine
keywords: 1; 8-cineole; Acetylcholinesterase; Alzheimer's disease; Mentha spicata L. subsp. spicata essential oil; N-methyl-Daspartate
  receptor; structure-biological activity relation