Evaluation of lipophilicity and drug‐likeness of donepezil‐like compounds using reversed‐phase thin‐layer chromatography

• Published in: Biomedical chromatography Vol. 38; no. 7; pp. e5867 - n/a
• Main Authors: Šegan, Sandra, Krunić, Mihajlo J., Andrić, Deana B., Šukalović, Vladimir B., Penjišević, Jelena Z., Jevtić, Ivana I.
• Format: Journal Article
• Language: English
• Published: England 01.07.2024
• Subjects: Blood-Brain Barrier - metabolism; blood–brain barrier permeability; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Chromatography, Reverse-Phase - methods; Chromatography, Thin Layer - methods; donepezil; Donepezil - chemistry; Donepezil - pharmacology; Hydrophobic and Hydrophilic Interactions; Indans - chemistry; lipophilicity; Piperidines - chemistry; Principal Component Analysis; reverse‐phased thin‐layer chromatography; donepezil; lipophilicity; reverse‐phased thin‐layer chromatography; blood–brain barrier permeability; principal component analysis
• ISSN: 0269-3879; 1099-0801; 1099-0801
• DOI: 10.1002/bmc.5867

Fourteen donepezil‐like acetylcholinesterase (AChE) inhibitors from our library were analyzed using reversed‐phase thin‐layer chromatography to assess their lipophilicity and blood–brain barrier permeability. Compounds possessed N‐benzylpiperidine and N,N‐diarylpiperazine moieties connected via a short carboxamide or amine linker. Retention parameters RM0, b, and C0 were considered as the measures of lipophilicity. Besides, logD of the investigated compounds was determined chromatographically using standard compounds with known logPow and logD values at pH 11. Experimentally obtained lipophilicity parameters correlated well with in silico generated results, and the effect of the nature of the linker between two pharmacophores and substituents on the arylpiperazine part of the molecule was observed. As a result of drug‐likeness analysis, both Lipinski's rule of five and Veber's rule parameters were determined, suggesting that examined compounds could be potential candidates for further drug development. Principal component analysis was performed to obtain an insight into a grouping of compounds based on calculated structural descriptors, experimentally obtained values of lipophilicity, and AChE inhibitory activity.