Quantitative Structure–Activity Relationship Study of Some Aspartic Acid Analogues to Correlate and Predict their Sweetness Potency

Abstract

A series of aspartame analogues and chemically modified derivatives was evaluated for their structure -activity relationship, as artificial sweeteners using Three Dimensional Quantitative Structure -Activity Relationship (3D-QSAR) with Genetic Functional Algorithm (GFA). A four-term equation was developed with conventional and crossvalidated coefficients of 0.753 and 0.660, respectively. 3D-QSAR studies of the same series were also performed by Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). The CoMFA model produced modest statistical significance with conventional and cross-validated correlation coefficients of 0.768 and 0.390, respectively. The combination of steric, electrostatic, hydrophobic, and H-bond acceptor fields in CoMSIA gave better results with conventional and cross-validated correlation coefficients of 0.927 and 0.585, respectively. The predictive ability of 3D-QSAR with GFA, CoMFA, and CoMSIA were determined using a test set of ten molecules giving predictive correlation coefficients of 0.375, 0.535, and 0.596, respectively, indicating better predictivity of CoMSIA compared to the other methods. Based on this information, some key features that may be used to design new sweeteners and predict their sweetness value have been identified.

Insight into Inhibitory Activity of Mycobacterial Dihydrofolate Reductase Inhibitors by In‐silico Molecular Modeling Approaches

“…The aim of CoMFA and CoMSIA studies was to generate the best predictive model for MAC DHFR inhibitors and to get deeper insight into the inhibitory potential of these molecules from the contours generated using CoMFA and CoMSIA descriptors [16,17]. The primary requirement for QSAR is a series of molecules with biological activity determined using same assay method showing considerable variation in activity.…”

Pharmacophore Refinement and 3D‐QSAR Studies of Histamine H3 Antagonists

“…The CoMFA or CoMSIA descriptors served as independent variables and pK i values as dependent variables in deducing 3D-QSAR models by PLS regression analysis method. A standard Leave-One-Out (LOO) cross-validation, and final fitting of equations with optimal number of components was followed, till models with highest r 2 and lowest PRESS were obtained [32]. The field type "stdev*-coeff" was used to obtain contour maps of CoMFA and CoMSIA analyses.…”

Estudio y aplicación de técnicas matemáticas de la teoría QSAR–QSPR en química analítica y química de los alimentos

“…5.2, AlogP indica que la hidrofobicidad de una molécula está directamente relacionado al dulzor relativo. Esta relación ha sido previamente presentada por Barker et al y Vepuri et al, 2007(Barker et al, 2002Vepuri et al, 2007). Adicionalmente, el uso del descriptor logP para describir el dulzor relativo también ha sido ampliamente discutido en la literatura (Greenberg, 1980;Iwamura, 1980Iwamura, , 1981Belitz et al, 1990;Drew et al, 1998;Jäger et al, 2000;Spillane et al, 2009;Briciu et al, 2010).…”

“…El análisis del AD del modelo muestra que los compuestos Periandrina III (h ii = 0.153) y el éster fencílico del ácido aspártico (h ii = 0.133) son los únicos compuestos del grupo de predicción fuera del AD teórico del modelo. (Kelly et al, 2005) CART 83 6 0.63 ------ (Tarko et al, 2005) MLR 123 4 --0.485 --0.507 (Tarko et al, 2006) MLR 136 4 0.66 0.652 ----121 5 0.85 0.399 ---- (Vepuri et al, 2007) MLR ( (Rojas et al, 2016b) Por otra parte, la Tabla 5.6 resume los diversos modelos publicados para la predicción del dulzor relativo. El modelo de la Ec.…”

“…En el año 2007, Vepuri et al (Vepuri et al, 2007) usaron 53 moléculas de análogos del aspartamo para desarrollar un modelo 3D-QSAR basado en un algoritmo funcional genético (GFA) y 4 descriptores moleculares. Posteriormente desarrollaron modelos basados en CoMFA y CoMSIA.…”