Synthesis of oleandrin derivatives and their cytotoxic activity

Yanzhi Zhang; Xubing Chen; Yang Zhou; Jinjun Hou; Huali Long; Zijia Zhang; Min Lei; Wanying Wu

doi:10.1016/j.steroids.2020.108650

Synthesis of oleandrin derivatives and their cytotoxic activity

Steroids. 2020 Jul:159:108650. doi: 10.1016/j.steroids.2020.108650. Epub 2020 Apr 28.

Authors

Yanzhi Zhang¹, Xubing Chen¹, Yang Zhou², Jinjun Hou², Huali Long², Zijia Zhang², Min Lei³, Wanying Wu⁴

Affiliations

¹ College of Pharmacy, Dali University, Dali 671000, PR China.
² Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
³ Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China. Electronic address: mlei@simm.ac.cn.
⁴ Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China. Electronic address: wanyingwu@simm.ac.cn.

PMID: 32360418
DOI: 10.1016/j.steroids.2020.108650

Abstract

A series of oleandrin-4'-yl ester derivatives were designed, synthesized, and evaluated for their proliferation inhibition activities against tumor cell lines. Cytotoxicity data revealed that the C4' moiety had an important influence on cytotoxic activity. Several compounds that we designed and synthesized exhibit significant in vitro antiproliferative activity against the tested tumor cell lines. Among the derivatives of OL, 4b-HCl not only had good anti-tumor activity but also had good water solubility. Furthermore, 4b-HCl can significantly inhibit tumor growth by 96.4% at a dose of 6 mg/kg/d by ip.

Keywords: Cardiac glycosides; Cytotoxicity; Natural product; OL-4′-yl ester; Oleandrin (OL).

Publication types

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

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cardenolides / chemical synthesis*
Cardenolides / chemistry
Cardenolides / pharmacology*
Cell Death / drug effects*
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Female
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Molecular Conformation
Neoplasms, Experimental / drug therapy
Neoplasms, Experimental / metabolism
Neoplasms, Experimental / pathology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Cardenolides
oleandrin