Enaminones 8: CoMFA and CoMSIA studies on some anticonvulsant enaminones

Abstract

Abstract3D QSAR studies comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were carried out on 26 structurally diverse subcutaneous pentylenetetrazol (scPTZ) active enaminone analogues, previously synthesized in our laboratory. CoMFA and CoMSIA were employed to generate models to define the specific structural and electrostatic features essential for enhanced binding to the putative GABA receptor. The 3D QSAR models demonstrated a reliable ability to predict the CLog P of the active anticonvulsant enaminones, resulting in a q 2 of 0.558 for CoMFA, and a q 2 of 0.698 for CoMSIA. The outcomes of the contour maps for both models provide detailed insight for the structural design of novel enaminone derivatives as potential anticonvulsant agents.

A Computational Approach for Exploring Carbohydrate Recognition by Lectins in Innate Immunity

“…It was found that the Galβ(1 → 4)GlcNAc and the Fucα(1 → 3)GlcNAc linkages exhibited quite specific conformational minima, which agreed with the experimental values of Φ/ψ = −77.0/131.6° for Galβ(1 → 4)GlcNAc, and Φ/ψ = −53.4/−90.9° for Fucα(1 → 3)GlcNAc. The overall rigidity of these linkages has been found in previous computational and experimental investigations (Yuriev et al, 2005; Jackson et al, 2009; Agostino et al, 2010). The GlcNAcβ(1 → 3)Gal linkage exhibited broader minima, also in agreement with previous findings (Jackson et al, 2009).…”

“…The overall rigidity of these linkages has been found in previous computational and experimental investigations (Yuriev et al, 2005; Jackson et al, 2009; Agostino et al, 2010). The GlcNAcβ(1 → 3)Gal linkage exhibited broader minima, also in agreement with previous findings (Jackson et al, 2009). The Ramachandran-like plots highlight that Glide, GOLD, and DOCK can effectively identify appropriate conformations of the Lewis X trisaccharide in the majority of instances; the experimentally determined conformations occur within the clusters obtained via the conformational search implementation of molecular docking.…”

A Substituted Anilino Enaminone Acts as a Novel Positive Allosteric Modulator of GABAA Receptors in the Mouse Brain

“…Meanwhile, several enaminones with chemical moieties different from KRS-5Me-4-OCF 3 were described to interact with GABA A receptors (Reitz et al, 1999;Yohannes et al, 2003;Hogenkamp et al, 2007). Other enaminone derivatives that probably target GABA receptors were provided by using the comparative molecular field analysis and comparative molecular similarity techniques, which can generate models to define the specific structural and electrostatic features essential for enhanced binding of enaminones to the putative GABA receptor (Jackson et al, 2009).…”

Cytotoxic Activity and Three-Dimensional Quantitative Structure Activity Relationship of 2-Aryl-1,8-naphthyridin-4-ones

“…The model of highest q 2 value and lowest standard error of prediction suggested the optimum number of components. Leave one out (LOO) cross-validation was used to estimate the predictive ability of the models (Jackson et al, 2009). …”