Synthesis and biological evaluation of novel steroidal 5α,8α-epidioxyandrost-6-ene-3β-ol-17-(O-phenylacetamide)oxime derivatives as potential anticancer agents

Ming Bu; Tingting Cao; Hongxia Li; Mingzhou Guo; Burton B Yang; Chengchu Zeng; Yue Zhou; Na Zhang; Liming Hu

doi:10.1016/j.bmcl.2017.06.048

Synthesis and biological evaluation of novel steroidal 5α,8α-epidioxyandrost-6-ene-3β-ol-17-(O-phenylacetamide)oxime derivatives as potential anticancer agents

Bioorg Med Chem Lett. 2017 Aug 15;27(16):3856-3861. doi: 10.1016/j.bmcl.2017.06.048. Epub 2017 Jun 21.

Authors

Ming Bu¹, Tingting Cao², Hongxia Li², Mingzhou Guo³, Burton B Yang⁴, Chengchu Zeng², Yue Zhou², Na Zhang², Liming Hu⁵

Affiliations

¹ Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China; College of Pharmacy, Qiqihar Medical University, Qiqihar 161006, China.
² Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
³ Chinese PLA General Hospital, Beijing 100853, China.
⁴ Sunnybrook Research Institute, University of Toronto, Toronto M4N3M5, Canada.
⁵ Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China; Beijing Key Laboratory of Environmental and Viral Oncology, Beijing University of Technology, Beijing 100124, China. Electronic address: huliming@bjut.edu.cn.

PMID: 28666736
DOI: 10.1016/j.bmcl.2017.06.048

Abstract

Inspired by the significant anti-cancer activity of our previously screened natural ergosterol peroxide (EP, 1), we synthesized and characterized a series of novel 5α,8α-epidioxyandrost-3β-ol-17-(O-phenylacetamide)oxime derivatives (9a-o). The anti-proliferative activity of the synthesized compounds against human hepatocellular carcinoma cells (HepG2, Sk-Hep1) and human breast cancer cells (MCF-7, MDA-MB231) were investigated. Compounds 9d, 9f, 9h, 9j and 9m displayed good anti-proliferative activity (most IC₅₀<20μM) in vitro. Furthermore, fluorescence imaging showed that the designed coumarin-9d conjugate (12) localized mainly in mitochondria, leading to enhanced anticancer activities over the parent structure.

Keywords: Cytotoxic activities; Endoperoxide; Ergosterol peroxide; Photooxygenation; Steroidal derivatives.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Crystallography, X-Ray
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Models, Molecular
Molecular Structure
Oximes / chemical synthesis
Oximes / chemistry
Oximes / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Oximes