Comparative QSAR Analysis of 3,5-bis (Arylidene)-4-Piperidone Derivatives: the Development of Predictive Cytotoxicity Models

Overview

Journal Iran J Pharm Res

Publisher Brieflands

Specialty Pharmacology

Date 2016 Sep 20

PMID 27642313

Citations 7

Authors

Najmeh Edraki

Umashankar Das

Bahram Hemateenejad

Jonathan R Dimmock

Ramin Miri

Affiliations

Soon will be listed here.

Abstract

1-[4-(2-Alkylaminoethoxy) phenylcarbonyl]-3,5-bis(arylidene)-4-piperidones are a novel class of potent cytotoxic agents. These compounds demonstrate low micromolar to submicromolar IC50 values against human Molt 4/C8 and CEM T-lymphocytes and murine leukemia L1210 cells. In this study, a comparative QSAR investigation was performed on a series of 3,5-bis (arylidene)-4-piperidones using different chemometric tools to develop the best predictive models for further development of analogs with improved cytotoxicity. All the QSAR models were validated by internal validation tests. The QSAR models obtained by GA-PLS method were considered the best as compared to MLR method. The best QSAR model obtained by GA-PLS analysis on L1210, CEM and Molt4/C8 demonstrated good predictively with R(2) pred values ranging from 0.94-0.80. Molecular density, topological (X2A) and geometrical indices of the molecules were found to be the most important factors for determining cytotoxic properties.

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