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Hybrids of arenobufagin and benzoisoselenazol reducing the cardiotoxicity of arenobufagin.

Abstract：

:Arenobufagin is a naturally occurring bufadienolide showing promising antitumor activity accompanied however with apparent cardiac toxicity. Following the recent discovery that oxidative damage possibly be an important cause of the cardiac toxicity of cardenolides, a strategy fusing the antitumor agent arenobufagin with a benzoisoselenazol fragment, a reactive oxygen species (ROS) scavenger, has been developed. Six novel hybrids were synthesized and their ROS scavenging activities as well as their in vitro cytotoxicity against the human hepatocellular carcinoma cell line HepG2, an adriamycin-resistant subline HepG2/ADM, and the human myocardial cell line AC16 were evaluated. The results indicate that the hybrids exhibit various degrees of in vitro ROS scavenging activities, and weaker cytotoxicity than that of arenobufagin against the myocardial cell line AC16. These findings suggest the feasibility of a strategy in which the cardiotoxicity of the potential antitumor agent arenobufagin is reduced.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Hou W,Huang ZX,Xu HG,Lin J,Zhang DM,Peng QL,Lin H,Chang YQ,Wang LH,Yao Z,Sun PH,Chen WM

doi

10.1016/j.bmcl.2018.08.038

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

3391-3394

issue

20

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(18)30714-5

journal_volume

28

pub_type

杂志文章

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