scholarly journals Quantative STRUCTURE Activity Relationship (QSAR) Study of a Series of Molecules Derived from 2,3-dihydro-1H- perimidine having Activity against Protein Tyrosine Phosphatase 1B

2021 ◽  
pp. 23-34
Author(s):  
Tuo Nanou Tiéba ◽  
Dembele Georges Stephane ◽  
Soro Doh ◽  
Konate Bibata ◽  
Kodjo Charles Guillaume ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
External Validation ◽  
Structure Activity Relationship ◽  
Quantitative Model ◽  
Activity Relationship ◽  
Protein Tyrosine Phosphatase 1B ◽  
Qsar Study ◽  
Protein Tyrosine ◽  
Structure Activity

In order to study the Quantitative Structure Activity Relationship (QSAR) against protein tyrosine phosphatase 1B and descriptors, we used a series of fourteen (14) molecules derived from perimidine. The compounds were optimized at the computational level B3LYP / 6-31 G (d, p), to obtain the descriptors of the model. This study was performed using the Linear Multiple Regression (MLR) method. This tool allowed us to obtain a quantitative model from the descriptors that are, the overall softness (S), the energy of the lowest vacant (ELUMO), the bond length l (N-C1). This model has good statistical performance (R2 = 0.958; RMCE = 0.110; F = 43.870). In addition, the external validation test of Tropsha and the domain of applicability from the levers were verified.

scholarly journals Complementary Quantitative Structure–Activity Relationship Models for the Antitrypanosomal Activity of Sesquiterpene Lactones

2018 ◽  
Vol 19 (12) ◽  
pp. 3721 ◽  
Author(s):  
Njogu M. Kimani ◽  
Josphat C. Matasyoh ◽  
Marcel Kaiser ◽  
Mauro S. Nogueira ◽  
Gustavo H. G. Trossini ◽  
...  
Keyword(s):  
Sesquiterpene Lactones ◽  
External Validation ◽  
Quantitative Structure Activity Relationship ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Quantitative Structure ◽  
Qsar Study ◽  
Data Set ◽  
Structure Activity ◽  
Antitrypanosomal Activity

Three complementary quantitative structure–activity relationship (QSAR) methodologies, namely, regression modeling based on (i) “classical” molecular descriptors, (ii) 3D pharmacophore features, and (iii) 2D molecular holograms (HQSAR) were employed on the antitrypanosomal activity of sesquiterpene lactones (STLs) toward Trypanosoma brucei rhodesiense (Tbr), the causative agent of the East African form of human African trypanosomiasis. In this study, an extension of a previous QSAR study on 69 STLs, models for a much larger and more diverse set of such natural products, now comprising 130 STLs of various structural subclasses, were established. The extended data set comprises a variety of STLs isolated and tested for antitrypanosomal activity within our group and is furthermore enhanced by 12 compounds obtained from literature, which have been tested in the same laboratory under identical conditions. Detailed QSAR analyses yielded models with comparable and good internal and external predictive ability. For a set of compounds as chemically diverse as the one under study, the models exhibited good coefficients of determination (R2) ranging from 0.71 to 0.85, as well as internal (leave-one-out Q2 values ranging from 0.62 to 0.72) and external validation coefficients (P2 values ranging from 0.54 to 0.73). The contributions of the various tested descriptors to the generated models are in good agreement with the results of previous QSAR studies and corroborate the fact that the antitrypanosomal activity of STLs is very much dependent on the presence and relative position of reactive enone groups within the molecular structure but is influenced by their hydrophilic/hydrophobic properties and molecular shape.

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