Non-linear assessment of anticancer activity of 17-picolyl and 17-picolinylidene androstane derivatives--chemometric guidelines for further syntheses

Eur J Pharm Sci. 2014 Oct 1:62:258-66. doi: 10.1016/j.ejps.2014.05.031. Epub 2014 Jun 11.

Abstract

The present paper deals with prediction of cytotoxic activity of 17-picolyl and 17-picolinylidene androstane derivatives toward androgen receptor negative prostate cancer cell line (PC-3). The prediction was achieved applying artificial neural networks (ANNs) method on the basis of molecular descriptors. The most important descriptors (skin permeability (SP), Madin-Darby canine kidney cell permeability (MDCK) and universal salt solubility factor (S+SF)) were selected by using stepwise selection coupled with partial least squares method. The ANN modelling was carried out in order to obtain reliable models which can facilitate further synthesis of androstane derivatives with high antiproliferative activity toward PC-3 cell line. The modelling procedure resulted in three ANN models with the best statistical performance. The obtained results show that the established ANN models can be applied for required purpose.

Keywords: Androstane derivatives; Artificial neural networks; Chemometrics; Molecular modelling; Prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstanes / pharmacology*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dogs
  • Humans
  • Madin Darby Canine Kidney Cells
  • Models, Biological*
  • Models, Molecular
  • Neural Networks, Computer*
  • Reproducibility of Results

Substances

  • Androstanes
  • Antineoplastic Agents