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Theoretical and experimental study of polycyclic aromatic compounds as β-tubulin inhibitors

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Abstract

In this work, through a docking analysis of compounds from the ZINC chemical library on human β-tubulin using high performance computer cluster, we report new polycyclic aromatic compounds that bind with high energy on the colchicine binding site of β-tubulin, suggesting three new key amino acids. However, molecular dynamic analysis showed low stability in the interaction between ligand and receptor. Results were confirmed experimentally in in vitro and in vivo models that suggest that molecular dynamics simulation is the best option to find new potential β-tubulin inhibitors.

Bennett’s acceptance ratio (BAR) method

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Acknowledgments

F.E.O.S. is the recipient of a scholarship (No. 419250) from Consejo Nacional de Ciencia y Tecnología (CONACyT), Mexico. We wish to express our gratitude to the Universidad Autonoma de Nuevo Leon (UANL), Instituto Politecnico Nacional (IPN), University of Texas Rio Grande Valley (UTRGV) and the University of Konstanz (UK) for their technical and financial support. In particular to Thomas U. Mayer for his support in the in vitro and in vivo assays, and Robert C. Jackson from UTRGV. G.R. holds a scholarship from the “Comision de Operacion y Fomento de Actividades Academicas” (COFAA-IPN) and the “Programa de Estimulos al Desempeño de los Investigadores” (EDI-IPN). All participants declare no conflict of interest.

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Authors and Affiliations

  1. Facultad de Ciencias Químicas. Av. Universidad s/n, Ciudad Universitaria, San Nicolás de los Garza, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, 64451, México

    Fabian E. Olazarán & Isaias Balderas-Rentería

  2. Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Boulevard del Maestro, s/n, Esq. Elías Piña, Reynosa, Tamualipas, Mexico, 88710

    Carlos A. García-Pérez & Gildardo Rivera

  3. Department of Chemistry, The University of Texas Rio Grande Valley, 1201 West University Drive, Edinburg, TX, 78539, USA

    Debasish Bandyopadhyay

  4. Centro de Investigación y de Estudios Avanzados del Instituto Politecnico Nacional, Unidad Monterrey, Apodaca, Nuevo León, 66600, México

    Angel D. Reyes-Figueroa

  5. Department of Biology, University of Konstanz, Universitätsstraβe 10, 78457, Konstanz, Germany

    Lars Henschke

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  1. Fabian E. Olazarán
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  2. Carlos A. García-Pérez
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  7. Gildardo Rivera
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Correspondence to Gildardo Rivera.

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Olazarán, F.E., García-Pérez, C.A., Bandyopadhyay, D. et al. Theoretical and experimental study of polycyclic aromatic compounds as β-tubulin inhibitors. J Mol Model 23, 85 (2017). https://doi.org/10.1007/s00894-017-3256-5

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