Holographic Quantitative Structure-Activity Relationships of Tryptamine Derivatives at NMDA, 5HT1A and 5HT2A Receptors

Molecules

Rungtiva Palangsuntikul¹  Heinz Berner²  Michael L. Berger³ 

[1] Biological Engineering Program, Faculty of Enigineering, King Mongkut’s University of Technology Thonburi, Bangmod campus, Bangkok 10140, Thailand;Institute for Theoretical Chemistry, University of Vienna, Währinger Strasse 17, Vienna 1090, Austria;Center for Brain Research, Medical University of Vienna, Spitalgasse 4, Vienna 1090, Austria

关键词: HQSAR;    NMDA receptor;    spermine;    tryptamine;    5HT_2A receptor;    5HT_1A receptor;   

DOI  :  10.3390/molecules18088799

来源: mdpi

【 摘 要 】

Tryptamine derivatives (Ts) were found to inhibit the binding of [³H]MK-801, [³H]ketanserin and [³H]8-OH-DPAT to rat brain membranes. [³H]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 [³H]ketanserin and [³H]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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.