Holographic Quantitative Structure-Activity Relationships of Tryptamine Derivatives at NMDA, 5HT(1A) and 5HT(2A) Receptors

Journal article

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Publication Details

Author list: Palangsuntikul R, Berner H, Berger ML, Wolschann P

Publisher: MDPI

Publication year: 2013

Journal: Molecules (1420-3049)

Volume number: 18

Issue number: 8

Start page: 8799

End page: 8811

Number of pages: 13

ISSN: 1420-3049

eISSN: 1420-3049

URL: https://www.mdpi.com/1420-3049/18/8/8799

Languages: English-Great Britain (EN-GB)

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Abstract

Tryptamine derivatives (Ts) were found to inhibit the binding of [H-3]MK-801, [H-3] ketanserin and [H-3]8-OH-DPAT to rat brain membranes. [H-3]MK-801 labels the NMDA (N-methyl-D-aspartate) receptor, a ionotropic glutamate receptor which controls synaptic plasticity and memory function in the brain, whereas [H-3]ketanserin and [H-3]8-OH-DPAT label 5HT(2A) and 5HT(1A) receptors, respectively. The inhibitory potencies of 64 Ts (as given by IC50 values) were correlated with their structural properties by using the Holographic QSAR procedure (HQSAR). This method uses structural fragments and connectivities as descriptors which were encoded in a hologram thus avoiding the usual problems with conformation and alignment of the structures. Four correlation equations with high predictive ability and appropriate statistical test values could be established. The results are visualized by generation of maps reflecting the contribution of individual structural parts to the biological activities.

Keywords

5HT(1A) receptor, 5HT(2A) receptor, HQSAR, NMDA receptor, spermine, tryptamine