Optimization of antiproliferative activity of substituted phenyl 4-(2-oxoimidazolidin-1-yl) benzenesulfonates: QSAR and CoMFA analyses

Vijay H. Masand, Devidas T. Mahajan, Ahmed M. Alafeefy, Bukhari Syed Nasir Abbas, Nahed N. Elsayed

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Multiple separate quantitative structure-activity relationships (QSARs) models were built for the antiproliferative activity of substituted Phenyl 4-(2-Oxoimidazolidin-1-yl)-benzenesulfonates (PIB-SOs). A variety of descriptors were considered for PIB-SOs through QSAR model building. Genetic algorithm (GA), available in QSARINS, was employed to select optimum number and set of descriptors to build the multi-linear regression equations for a dataset of PIB-SOs. The best three parametric models were subjected to thorough internal and external validation along with Y-randomization using QSARINS, according to the OECD principles for QSAR model validation. The models were found to be statistically robust with high external predictivity. The best three parametric model, based on steric, 3D- and finger print descriptors, was found to have R2 = 0.91, Rex2 = 0.89, and CCCex = 0.94. The CoMFA model, which is based on a combination of steric and electrostatic effects and graphically inferred using contour plots, gave F = 229.34, RCV2 = 0.71 and R2 = 0.94. Steric repulsion, frequency of occurrence of carbon and nitrogen at topological distance of seven, and internal electronic environment of the molecule were found to have correlation with the anti-tumor activity of PIB-SOs.

Original languageEnglish
Pages (from-to)230-237
Number of pages8
JournalEuropean Journal of Pharmaceutical Sciences
Volume77
DOIs
Publication statusPublished - 30 Jun 2015

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Benzenesulfonates
Quantitative Structure-Activity Relationship
Random Allocation
Static Electricity
Fingers
Linear Models
Nitrogen
Carbon
Neoplasms

Keywords

  • Antiproliferative activity
  • CoMFA
  • QSAR
  • Substituted phenyl 4-(2-oxoimidazolidin-1-yl)-benzenesulfonates

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Medicine(all)

Cite this

Optimization of antiproliferative activity of substituted phenyl 4-(2-oxoimidazolidin-1-yl) benzenesulfonates : QSAR and CoMFA analyses. / Masand, Vijay H.; Mahajan, Devidas T.; Alafeefy, Ahmed M.; Syed Nasir Abbas, Bukhari; Elsayed, Nahed N.

In: European Journal of Pharmaceutical Sciences, Vol. 77, 30.06.2015, p. 230-237.

Research output: Contribution to journalArticle

Masand, Vijay H. ; Mahajan, Devidas T. ; Alafeefy, Ahmed M. ; Syed Nasir Abbas, Bukhari ; Elsayed, Nahed N. / Optimization of antiproliferative activity of substituted phenyl 4-(2-oxoimidazolidin-1-yl) benzenesulfonates : QSAR and CoMFA analyses. In: European Journal of Pharmaceutical Sciences. 2015 ; Vol. 77. pp. 230-237.
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