Rocha_2018_J.Biomol.Struct.Dyn__1

Reference

Title : Cooperative hydrogen bonds and mobility of the non-aromatic ring as selectivity determinants for human acetylcholinesterase to similar anti-Alzheimer's galantaminics: a computational study - Rocha_2018_J.Biomol.Struct.Dyn__1
Author(s) : Rocha REO , Lima LHF
Ref : J Biomol Struct Dyn , :1 , 2018
Abstract : Galantamine (Gnt) is a natural alkaloid inhibitor of acetylcholinesterase and is presently one of the most used drugs in the treatment against Alzheimer's disease during both the initial and intermediate stages. Among several natural Gnt derivatives, sanguinine (Sng) and lycoramine (Lyc) attract attention because of the way their subtle chemical differences from Gnt lead to drastic and opposite distinctions in inhibitory effects. However, to date there is no solved structure for these natural derivatives. In the present study, we applied computational modeling and free energy calculation methods to better elucidate the molecular basis of the subtle distinctions between these derivatives and Gnt. The results showed that differences in the mobility of the non-aromatic ring carried by the Lyc-like sp(2)-sp(3) modification display drastic conformational, vibrational, and entropic penalties at binding compared to Gnt. Additionally, the establishment of a stronger hydrogen bond network added enthalpic advantages for the linkage of the Sng-like methoxy-hydroxy substituted ligands. These results, which suggest an affinity ranking in agreement with that found in the literature, provided insights that are helpful for future planning and development of new anti-Alzheimer's disease drugs.
ESTHER : Rocha_2018_J.Biomol.Struct.Dyn__1
PubMedSearch : Rocha_2018_J.Biomol.Struct.Dyn__1
PubMedID: 29697300

Related information

Inhibitor SanguinineGalanthamine

Citations formats

Rocha REO, Lima LHF (2018)
Cooperative hydrogen bonds and mobility of the non-aromatic ring as selectivity determinants for human acetylcholinesterase to similar anti-Alzheimer's galantaminics: a computational study
J Biomol Struct Dyn :1

Rocha REO, Lima LHF (2018)
J Biomol Struct Dyn :1

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    [author] => Rocha REO || Lima LHF
    [year] => 2018
    [title] => Cooperative hydrogen bonds and mobility of the non-aromatic ring as selectivity determinants for human acetylcholinesterase to similar anti-Alzheimer's galantaminics: a computational study
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            [content] => Galantamine (Gnt) is a natural alkaloid inhibitor of acetylcholinesterase and is presently one of the most used drugs in the treatment against Alzheimer's disease during both the initial and intermediate stages. Among several natural Gnt derivatives, sanguinine (Sng) and lycoramine (Lyc) attract attention because of the way their subtle chemical differences from Gnt lead to drastic and opposite distinctions in inhibitory effects. However, to date there is no solved structure for these natural derivatives. In the present study, we applied computational modeling and free energy calculation methods to better elucidate the molecular basis of the subtle distinctions between these derivatives and Gnt. The results showed that differences in the mobility of the non-aromatic ring carried by the Lyc-like sp(2)-sp(3) modification display drastic conformational, vibrational, and entropic penalties at binding compared to Gnt. Additionally, the establishment of a stronger hydrogen bond network added enthalpic advantages for the linkage of the Sng-like methoxy-hydroxy substituted ligands. These results, which suggest an affinity ranking in agreement with that found in the literature, provided insights that are helpful for future planning and development of new anti-Alzheimer's disease drugs.
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