title: Optimization of antiproliferative activity of substituted phenyl 4-(2-oxoimidazolidin-1-yl) benzenesulfonates: QSAR and CoMFA analyses.
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 R(2)=0.91, R(2)ex=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, R(2)CV=0.71 and R(2)=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.
authors.affiliation: Department of Chemistry, Vidya Bharati College, Camp, Amravati, Maharashtra 444 602, India. Electronic address: vijaymasand@gmail.com.
authors.forename: Vijay H
authors.initials: VH
authors.lastname: Masand
authors.affiliation: Department of Chemistry, Vidya Bharati College, Camp, Amravati, Maharashtra 444 602, India.
authors.forename: Devidas T
authors.initials: DT
authors.lastname: Mahajan
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Alkharj 11942, Saudi Arabia.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Alafeefy
authors.affiliation: Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
authors.forename: Syed Nasir Abbas
authors.initials: SN
authors.lastname: Bukhari
authors.affiliation: Department of Chemistry, College of Science, "Girls Section", King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia; National Organization for Drug Control and Research, Giza 35521, Egypt.
authors.forename: Nahed N
authors.initials: NN
authors.lastname: Elsayed
mesh_terms: D001557:Benzenesulfonates / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D001557:Benzenesulfonates
keywords: Antiproliferative activity; CoMFA; QSAR; Substituted phenyl 4-(2-oxoimidazolidin-1-yl)-benzenesulfonates