A computational insight into acetylcholinesterase inhibitory activity of a new lichen depsidone

Abstract

Acetylcholinesterase (AChE) inhibitors are yet the best drugs currently available for the management of Alzheimer's disease. The recent phytochemical investigation has led to the isolation of a new depsidone 1 with moderate AChE activity (1 μg). This work was focused on its electronic properties analysed using commercially available programs. Both the active depsidone molecule 1 and galanthamine showed to have higher HOMO energies than the inactive depsidones 2-4, isolated from the same lichen species. However, the amino depsidone derivative 7, whose structure was proposed using computational approaches, is expected to be more active AChE inhibitor than the depsidone 1, due to the improved HOMO energy value. In addition, the molecular docking study indicated that the compound 7 has ability to make the well-known interactions of potent AChE inhibitors with the enzyme active site. The data presented herein support the design of novel AChE inhibitors based on the depsidone scaffold.

Spectroscopic Identifications, Molecular Docking, Neuronal Growth and Enzyme Inhibitory Activities of Steroidal Nitro Olefin: Quantum Chemical Study

“…The capacity of molecular electron donation can be well explained by studying the values of HOMO energy, increasing the energy of HOMO, facilitating the process of oxidation. The arrangement of HOMO and LUMO is important to determine the highly appropriate region of the ligand for receptor interaction . In figure , HOMO and LUMO are mainly delocalized over the NO 2 group and some ring portion (R1 and R2).…”

“…HOMO, LUMO, HOMO‐1 and LUMO+1 contribute significantly to the inhibitory activity of AChE as reported in literature . The active inhibitors are found to have higher HOMO energy than the inactive one …”

“…The arrangement of HOMO and LUMO is important to determine the highly appropriate region of the ligand for receptor interaction. [56] In figure 6, HOMO and LUMO are mainly delocalized over the NO 2 group and some ring portion (R1 and R2). HOMO-LUMO excitation thus explains the transfer of charge within a certain part of the molecule (NO 2 group, R1 and R2 ring) (table 4).…”

Synthesis, molecular modeling, and biological evaluation of 4‐[5‐aryl‐3‐(thiophen‐2‐yl)‐4,5‐dihydro‐1H‐pyrazol‐1‐yl] benzenesulfonamides toward acetylcholinesterase, carbonic anhydrase I and II enzymes

“…Furthermore, several studies report the importance of dipole moment and the energy of frontier molecular orbitals having important contributions to the AChE inhibitory activity . Hence, we found it necessary to calculate the quantum chemical properties of TP1–10 and of TAC for comparison, at a high and accurate level (M06‐L/6‐31+G(d,p)//AM1) .…”

Computer-aided Design of Chalcone Derivatives as Lead Compounds Targeting Acetylcholinesterase

“…Chalcones or 1,3-diphenyl-2-propene-1-one can be obtained both from the plants (Abdelwahab, 2013;Adewusi et al, 2010) and from the synthetic way due to condensation reaction between substituted aromatic aldehyde with substituted acetophenones in alkaline condition (Jayapal and Sreedhar, 2010). Nevertheless, it is important to consider the structure-activity relationship and computational approach in designing more active AChE inhibitors (Andersson et al, 2013;Ece et al, 2015).…”