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

61Citations
Citations of this article
47Readers
Mendeley users who have this article in their library.
Get full text

Abstract

Abiraterone, a steroidal cytochrome P450 17α-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. © 2008 American Chemical Society.

Cite

CITATION STYLE

APA

Pinto-Bazurco Mendieta, M. A. E., Negri, M., Jagusch, C., Müller-Vieira, U., Lauterbach, T., & Hartmann, R. W. (2008). Synthesis, biological evaluation, and molecular modeling of abiraterone analogues: Novel CYP17 inhibitors for the treatment of prostate cancer. Journal of Medicinal Chemistry, 51(16), 5009–5018. https://doi.org/10.1021/jm800355c

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free