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Molecular modelling and quantitative structure-activity relationship studies of anatoxin-a and epibatidine derivatives with affinity to rodent nAChR receptors

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Abstract

Anatoxin-a and epibatidine are natural toxins with a high affinity to nicotinic acetylcholine receptors (nAChR). Nicotinic ligands have the potential to become novel therapeutic agents for various cognitive disorders such as Alzheimer’s and Parkinson’s diseases. The determination of the physicochemical and biological properties of anatoxin-a and epibatidine derivatives is important because these might lead to the development of new cholinergic therapeutic agents. To study these features, the toxins and a set of their derivatives were subjected to a molecular modelling study and QSAR analysis. The structural analyses indicated that the geometric and steric features are important determinants of the compound’s activities. The descriptors selected for the QSAR model also highlighted the roles of the geometric and steric features, together with the importance of electronic features.

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Authors and Affiliations

  1. Theoretical Medicinal and Environmental Chemistry Laboratory (LQMAT). Department of Pharmacy, Western Paraná State University (UNIOESTE), 2069 Universitária St., 85819110, Cascavel, PR, Brazil

    Eduardo Borges de Melo

  2. Biotechnology Institute, University of Caxias do Sul (UCS), 1130 Francisco Getulio Vargas St., 95070570, Caxias do Sul, RS, Brazil

    Sidnei Moura e Silva

  3. Course of Pharmacy, Federal University of Pampa (UNIPAMPA), BR472, KM592, P.O. Box 118, 97500970, Uruguaiana, RS, Brazil

    Fávero Reisdorfer Paula

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  1. Eduardo Borges de Melo
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  2. Sidnei Moura e Silva
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  3. Fávero Reisdorfer Paula
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Correspondence to Eduardo Borges de Melo.

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de Melo, E.B., Moura e Silva, S. & Paula, F.R. Molecular modelling and quantitative structure-activity relationship studies of anatoxin-a and epibatidine derivatives with affinity to rodent nAChR receptors. Chem. Pap. 68, 1121–1131 (2014). https://doi.org/10.2478/s11696-014-0545-7

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