Synthesis and cytotoxicity evaluation of 4'-amino-4'-dehydroxyloleandrin derivatives

Hu Chen; Min Lei; Biao Ma; Miao Liu; Dean Guo; Xuan Liu; Lihong Hu

doi:10.1016/j.fitote.2016.07.002

Synthesis and cytotoxicity evaluation of 4'-amino-4'-dehydroxyloleandrin derivatives

Fitoterapia. 2016 Sep:113:85-90. doi: 10.1016/j.fitote.2016.07.002. Epub 2016 Jul 16.

Authors

Hu Chen¹, Min Lei², Biao Ma³, Miao Liu³, Dean Guo³, Xuan Liu⁴, Lihong Hu⁵

Affiliations

¹ Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
² State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 201203, PR China. Electronic address: [email protected].
³ State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 201203, PR China.
⁴ State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 201203, PR China. Electronic address: [email protected].
⁵ Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China; State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 201203, PR China. Electronic address: [email protected].

PMID: 27431773
DOI: 10.1016/j.fitote.2016.07.002

Abstract

A series of C4'-substituted oleandrin analogues were designed, synthesized and evaluated for their cytotoxicity towards human cervical carcinoma cell line (HeLa). The structure-activity relationships (SARs) of these compounds were summarized in this paper, and 4'-α-amino-4'-dehydroxyloleandrin 4a (IC50=21.7nM) and 4'-β-amino-4'-dehydroxyloleandrin 4b (IC50=10.9nM) exhibited stronger cytotoxicity compared with oleandrin (IC50=33.3nM). Furthermore, the cytotoxicity of these two compounds towards another five human cancer cell lines (NCI-H266, A549, Jurkat, HL-60 and PC-3) was also evaluated and the IC50 values of β-amino derivative 4b were approximately 2-3 folds lower than that of oleandrin.

Keywords: Antitumor agent; Cytotoxicity; Natural product; Oleandrin; Structure-activity relationships (SARs).

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Cardenolides / chemical synthesis
Cardenolides / chemistry*
Cell Line, Tumor
Drug Design
Drug Screening Assays, Antitumor
HeLa Cells / drug effects
Humans
Molecular Structure
Structure-Activity Relationship

Substances

4'-alpha-amino-4'-dehydroxyloleandrin 4a
Antineoplastic Agents
Cardenolides
oleandrin