QSAR studies on aminopyrazoles for the prediction of inhibition of CDK2/Cyclin A as antitumor agents

Cylin dependent kinases (CDKs) have emerged as novel mechanistic target due to their direct involvement in underlying genetic changes during the cancerous state. In order to identify the essential physiochemical parameters for CDK2 inhibitory activity in some 3-aminopyrazole derivatives, Quantitativ...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Jain, Sonika, Kishore, Dharma, Dwivedi, Jaya
Formato: Articulo
Lenguaje:Inglés
Publicado: 2011
Materias:
Farmacia
QSAR; Hansch analysis; 3-aminopyrazole derivatives; Lipinski's rule
Quinasas Ciclina-Dependientes
Pirazoles
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/8389
http://www.latamjpharm.org/resumenes/30/10/LAJOP_30_10_1_1.pdf
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-8389
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Farmacia
QSAR; Hansch analysis; 3-aminopyrazole derivatives; Lipinski's rule
Quinasas Ciclina-Dependientes
Pirazoles
spellingShingle Farmacia
QSAR; Hansch analysis; 3-aminopyrazole derivatives; Lipinski's rule
Quinasas Ciclina-Dependientes
Pirazoles
Jain, Sonika
Kishore, Dharma
Dwivedi, Jaya
QSAR studies on aminopyrazoles for the prediction of inhibition of CDK2/Cyclin A as antitumor agents
topic_facet Farmacia
QSAR; Hansch analysis; 3-aminopyrazole derivatives; Lipinski's rule
Quinasas Ciclina-Dependientes
Pirazoles
description Cylin dependent kinases (CDKs) have emerged as novel mechanistic target due to their direct involvement in underlying genetic changes during the cancerous state. In order to identify the essential physiochemical parameters for CDK2 inhibitory activity in some 3-aminopyrazole derivatives, Quantitative Structure-Activity Relationship (QSAR) studies have been carried out on a series of total 35 compounds (taking 24 and 11 molecules in trainings set and test set respectively) using the multiple linear regression MLR) method. Among the generated models, the best QSAR model with good correlation coefficient (r<sup>2</sup> = 0.643) along high statistical significance (> 99.9 %) well explained variance in activity for both training and test set molecules (Pred. r<sup>2</sup> = 0.632). The two dimensional QSAR studies revealed that the activity is positively controlled by the indicator parameter (I), electronic parameter (field effect, F) and hydrophobic fragmentation constant (Fr) of substituents. Apart from that one of the interesting finding is that this model well discriminates between the Molar refractivity (MR) and hydrophobic fragmentation constant (Fr) in prediction of inhibitory activities based on the regression coefficient and associated error. Further the calculation of important descriptors like log P, hydrogen bond donor and acceptors etc. indicates the potential of these molecules in clinical trial as an anticancer drug.
format Articulo
Articulo
author Jain, Sonika
Kishore, Dharma
Dwivedi, Jaya
author_facet Jain, Sonika
Kishore, Dharma
Dwivedi, Jaya
author_sort Jain, Sonika
title QSAR studies on aminopyrazoles for the prediction of inhibition of CDK2/Cyclin A as antitumor agents
title_short QSAR studies on aminopyrazoles for the prediction of inhibition of CDK2/Cyclin A as antitumor agents
title_full QSAR studies on aminopyrazoles for the prediction of inhibition of CDK2/Cyclin A as antitumor agents
title_fullStr QSAR studies on aminopyrazoles for the prediction of inhibition of CDK2/Cyclin A as antitumor agents
title_full_unstemmed QSAR studies on aminopyrazoles for the prediction of inhibition of CDK2/Cyclin A as antitumor agents
title_sort qsar studies on aminopyrazoles for the prediction of inhibition of cdk2/cyclin a as antitumor agents
publishDate 2011
url http://sedici.unlp.edu.ar/handle/10915/8389
http://www.latamjpharm.org/resumenes/30/10/LAJOP_30_10_1_1.pdf
work_keys_str_mv AT jainsonika qsarstudiesonaminopyrazolesforthepredictionofinhibitionofcdk2cyclinaasantitumoragents
AT kishoredharma qsarstudiesonaminopyrazolesforthepredictionofinhibitionofcdk2cyclinaasantitumoragents
AT dwivedijaya qsarstudiesonaminopyrazolesforthepredictionofinhibitionofcdk2cyclinaasantitumoragents
bdutipo_str Repositorios
_version_ 1764820488155037696

Ejemplares similares