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.
Method: 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).
Conclusion: 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