Plausible compounds drawn from plants as curative agents for neurodegeneration: An in-silico approach

Classification of chemical compounds of plants as a source of medicaments for neurodegenerative diseases through computer screening is an efficient process in drug discovery, in advance of laboratory testing and clinical trials. The onset of neurodegenerative disorders incarcerates both sufferers and their families mentally and financially. This investigation emphasises the search for potent compounds via a computational approach, as an initial path towards the treatment of the neurodegenerative diseases Alzheimer's (AD), Parkinson's (PD), prion, and Huntington's (HD) diseases. The therapeutic strategy considered here is chelation therapy, emanated from the heightened levels of metal ions, which play an imperative role in the pathogenesis of all four neurodegenerative disorders mentioned. Hence, potent compounds from Sri Lankan plants to function as lead compounds have been identified for Cu(II), Fe(III), Zn(II), and Al(III) ions, from a library of around 200 chemical compounds, using an umbrella sampling molecular dynamics computational approach where the chelating ability of compounds for the metal ion is assessed in terms of binding free energy. Calculations reveal that 12 Sri Lankan plants possess compounds that could be considered as starting points of leads for AD, PD and prion disease. However, no compound was potentially useful for the HD category, according to the study. Potential of mean force of Al³⁺ binding to (-)-5-methylmellin found in Semecarpus walkeri with two representative configurations.

Keywords: Chelation therapy; Free energy; Metal ions; Neurodegeneration; Umbrella sampling.