Molecular Diversity

, Volume 20, Issue 3, pp 771–780 | Cite as

Activity landscape analysis of novel 5\(\upalpha \)-reductase inhibitors

  • J. Jesús Naveja
  • Francisco Cortés-Benítez
  • Eugene Bratoeff
  • José L. Medina-FrancoEmail author
Short Communication


Inhibitors of the enzyme 5\(\upalpha \)-reductase (5aR) are promising therapeutic agents for the treatment of benign prostatic hyperplasia (BPH) and prostate cancer. The lack of structural data of the enzyme 5aR prompts the application of ligand-based approaches to systematically explore the activity landscape of 5aR inhibitors. As part of an effort to develop inhibitors of this enzyme for the treatment of BPH, herein we discuss a chemoinformatic-based analysis of the activity landscape of a novel set of 53 novel pregnane and androstene compounds. It was found that, in general, for each pair of compounds in the set, as the structure similarity of the compounds increases the corresponding potency difference decreases. These results are in agreement with an overall smooth activity landscape. However, two potent activity cliff generators were identified pointing to specific small structural changes that have a large impact on the inhibition of 5aR.


Activity cliff generators Benign prostatic hyperplasia Chemical space Chemoinformatics Prostatic 5\(\upalpha \)-reductase Structure–activity relationships 



5\(\upalpha \)-Reductase


Activity landscape modeling


Androgen receptor


Benign prostatic hyperplasia


5\(\upalpha \)-Dihydrotestosterone


Extended connectivity fingerprints




Prostate cancer


Principal component analysis


Structure–activity relationships


Structure–activity similarity




Tanimoto coefficient



FCB thanks the Consejo Nacional de Ciencia y Tecnología (CONACyT) by the Fellowship Awarded (Number 255249) to carry out the PhD studies. JLMF acknowledges the National Autonomous University of Mexico (UNAM) for Grant PAIP 5000-9163.

Supplementary material

11030_2016_9659_MOESM1_ESM.pdf (324 kb)
Supplementary material 1 (pdf 324 KB)


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • J. Jesús Naveja
    • 1
    • 2
  • Francisco Cortés-Benítez
    • 1
  • Eugene Bratoeff
    • 1
  • José L. Medina-Franco
    • 1
    Email author
  1. 1.Departamento de Farmacia, Facultad de QuímicaUniversidad Nacional Autónoma de MéxicoMexicoMexico
  2. 2.Facultad de Medicina, PECEMUniversidad Nacional Autónoma de MéxicoMexicoMexico

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