Synthesis, biological evaluation, and molecular modeling of abiraterone analogues: novel CYP17 inhibitors for the treatment of prostate cancer

  • Pinto-Bazurco Mendieta M
  • Negri M
  • Jagusch C
 et al. 
  • 4

    Readers

    Mendeley users who have this article in their library.
  • N/A

    Citations

    Citations of this article.

Abstract

Abiraterone, a steroidal cytochrome P450 17alpha-hydroxylase-17,20-lyase inhibitor (CYP17), is currently undergoing phase II clinical trials as a potential drug for the treatment of androgen-dependent prostate cancer. Since steroidal compounds often show side effects attributable to their structure, we have tried to replace the sterane scaffold by nonsteroidal core structures. The design and synthesis of 20 new abiraterone mimetics are described. Their activities have been tested with recombinant human CYP17 expressed in E. coli. Promising compounds were further evaluated for selectivity against CYP11B1, CYP11B2, and the hepatic CYP3A4. Compounds 19 and 20 showed comparable activity to abiraterone (IC50 values of 144 and 64 nM vs 72 nM) and similar or even better selectivity against the other CYP enzymes. Selected compounds were also docked into our homology model, and the same binding modes as for abiraterone were found.

Author-supplied keywords

  • Androstenes
  • Androstenols/*chemical synthesis/*pharmacology/the
  • Biphenyl Compounds/chemical synthesis/pharmacology
  • Enzyme Inhibitors/*chemical synthesis/*pharmacolog
  • Humans
  • Male
  • Models
  • Molecular
  • Prostatic Neoplasms/*drug therapy
  • Recombinant Proteins/drug effects
  • Steroid 17-alpha-Hydroxylase/*antagonists & inhibi

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • M A Pinto-Bazurco Mendieta

  • M Negri

  • C Jagusch

  • U Muller-Vieira

  • T Lauterbach

  • R W Hartmann

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free