3D-QSAR and docking studies of pentacycloundecylamines at the sigma-1 (sigma1) receptor.

Title

3D-QSAR and docking studies of pentacycloundecylamines at the sigma-1 (sigma1) receptor.

Creator

Geldenhuys Werner J; Novotny Nicholas; Malan Sarel F; Van der Schyf Cornelis J

Publisher

Bioorganic & medicinal chemistry letters

Date

2013
2013-03

Description

Pentacycloundecylamine (PCU) derived compounds have been shown to be promising lead structures for the development of novel drug candidates aimed at a variety of neurodegenerative and psychiatric diseases. Here we show for the first time a 3D quantitative structure-activity relationship (3D-QSAR) for a series of aza-PCU-derived compounds with activity at the sigma-1 (sigma1) receptor. A comparative molecular field analysis (CoMFA) model was developed with a partial least squares cross validated (q(2)) regression value of 0.6, and a non-cross validated r(2) of 0.9. The CoMFA model was effective at predicting the sigma-1 activities of a test set with an r(2) \textgreater0.7. We also describe here the docking of the PCU-derived compounds into a homology model of the sigma-1 (sigma1) receptor, which was developed to gain insight into binding of these cage compounds to the receptor. Based on docking studies we evaluated in a [(3)H]pentazocine binding assay an oxa-PCU, NGP1-01 (IC50=1.78muM) and its phenethyl derivative (IC50=1.54muM). Results from these studies can be used to develop new compounds with specific affinity for the sigma-1(sigma1) receptor.

Subject

*Quantitative Structure-Activity Relationship; Amines/*chemistry/metabolism; Aza Compounds/chemistry; Binding Sites; Kinetics; Molecular Docking Simulation; Protein Binding; Protein Structure; Receptors; sigma/*chemistry/metabolism; Tertiary

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

1707–1711

Issue

6

Volume

23

Citation

Geldenhuys Werner J; Novotny Nicholas; Malan Sarel F; Van der Schyf Cornelis J, “3D-QSAR and docking studies of pentacycloundecylamines at the sigma-1 (sigma1) receptor.,” NEOMED Bibliography Database, accessed December 3, 2021, https://neomed.omeka.net/items/show/3499.

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