Illuminating cytochrome P450 binding: Ru(ii)-caged inhibitors of CYP17A1

Ao Li; Rahul Yadav; Jessica K White; Mackenzie K Herroon; Brian P Callahan; Izabela Podgorski; Claudia Turro; Emily E Scott; Jeremy J Kodanko

doi:10.1039/c7cc01459g

Illuminating cytochrome P450 binding: Ru(ii)-caged inhibitors of CYP17A1

Chem Commun (Camb). 2017 Mar 28;53(26):3673-3676. doi: 10.1039/c7cc01459g.

Authors

Ao Li¹, Rahul Yadav², Jessica K White³, Mackenzie K Herroon⁴, Brian P Callahan⁵, Izabela Podgorski⁶, Claudia Turro³, Emily E Scott², Jeremy J Kodanko⁷

Affiliations

¹ Department of Chemistry, Wayne State University, Detroit, MI 48202, USA. jkodanko@chem.wayne.edu.
² Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
³ Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, USA.
⁴ Department of Pharmacology, School of Medicine, Wayne State University, Detroit, Michigan 48201, USA.
⁵ Department of Chemistry, Binghamton University, Binghamton, New York 13902, USA.
⁶ Department of Pharmacology, School of Medicine, Wayne State University, Detroit, Michigan 48201, USA and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201, USA.
⁷ Department of Chemistry, Wayne State University, Detroit, MI 48202, USA. jkodanko@chem.wayne.edu and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201, USA.

Abstract

New Ru(ii)-caged abiraterone complexes were synthesized that exhibit strong absorption in the visible region and release the steroidal CYP17A1 inhibitor abiraterone upon exposure to low energy visible light in buffer and prostate cancer cells. Photoinduced release results in abiraterone binding to its CYP17A1 target in an inhibitory mode.

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Binding Sites / drug effects
Cell Line, Tumor
Cell Survival / drug effects
Coordination Complexes / chemical synthesis
Coordination Complexes / chemistry
Coordination Complexes / pharmacology*
Cytochrome P-450 Enzyme Inhibitors / chemical synthesis
Cytochrome P-450 Enzyme Inhibitors / chemistry
Cytochrome P-450 Enzyme Inhibitors / pharmacology*
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Light
Male
Molecular Structure
Prostatic Neoplasms / drug therapy*
Prostatic Neoplasms / metabolism
Ruthenium / chemistry
Ruthenium / pharmacology*
Steroid 17-alpha-Hydroxylase / antagonists & inhibitors*
Steroid 17-alpha-Hydroxylase / metabolism
Structure-Activity Relationship

Substances

Antineoplastic Agents
Coordination Complexes
Cytochrome P-450 Enzyme Inhibitors
Ruthenium
CYP17A1 protein, human
Steroid 17-alpha-Hydroxylase

Abstract

MeSH terms

Substances

Grants and funding