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Triptan partition in model membranes

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Abstract

In this work, we report a molecular dynamics simulations study of protonated triptans, sumatriptan and naratriptan, in a fully hydrated bilayer of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyl-choline (POPC). The simulations were carried out at two concentrations for each drug. Our results show partition between the lipid head-water interphase and water phase for both triptans, with increasing access to the water phase with increasing concentrations. The triptans were stabilized at the interphase through different specific interactions with the POPC bilayer such as hydrogen bonds, salt bridges, and cation-π. Besides, sumatriptan and naratriptan protonated molecules have no access to the hydrophobic region of the bilayer at the studied conditions. Similar results were found for both drugs, however protonated naratriptan shows slightly higher affinity for the water phase. This behavior was attributed to the bulky lateral amino group in its structure under the studied conditions (drugs were originally placed at the water phase). This work represents a first insight to the comprehensive understanding of triptan partition in model membranes.

Snapshot of the bilayer containing protonated naratriptan, at high concentration: POPC lipids are shown in light brown (N and P atoms represented by violet and orange spheres, respectively) and naratriptan in green. Water molecules were removed for visualization purposes. Besides, two pairs of lipid-naratriptan were highlighted in blue and red respectively, indicating specific interactions.

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Acknowledgments

This work was supported with funds from Agencia Nacional de Promoción Científica y Técnica (PICT (2008/310), associated to Project PRH 2007 N°71). M.P. is a member of the Research Career from Consejo Nacional de Investigaciones Científicas y Técnicas (R. Argentina). I.W. is a Ph. D. fellow of the Agencia Nacional de Promoción Científica y Técnica (R. Argentina).

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Authors and Affiliations

  1. Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, Buenos Aires, CP1113, Argentina

    Irene Wood & Mónica Pickholz

  2. Instituto Nanobiotec, Consejo Nacional de Investigaciones Científicas y Técnica (CONICET), Rivadavia 1917, Buenos Aires, CP1033, Argentina

    Mónica Pickholz

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  1. Irene Wood
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  2. Mónica Pickholz
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Correspondence to Mónica Pickholz.

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This paper belongs to Topical Collection Brazilian Symposium of Theoretical Chemistry (SBQT2013)

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Wood, I., Pickholz, M. Triptan partition in model membranes. J Mol Model 20, 2463 (2014). https://doi.org/10.1007/s00894-014-2463-6

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  • DOI: https://doi.org/10.1007/s00894-014-2463-6

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