当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Novel anticancer oridonin derivatives possessing a diazen-1-ium-1,2-diolate nitric oxide donor moiety: Design, synthesis, biological evaluation and nitric oxide release studies.

Novel anticancer oridonin derivatives possessing a diazen-1-ium-1,2-diolate nitric oxide donor moiety: Design, synthesis, biological evaluation and nitric oxide release studies.

Abstract：

:Oridonin (1) is a complex ent-kaurane diterpenoid with unique antitumor profile, which is isolated from Isodon rubescens. In order to develop novel derivatives of oridonin with improved potency, a series of nitric oxide (NO)-releasing oridonin derivatives were synthesized by coupling diazeniumdiolates with oridonin and its semisynthesized analogues. Their in vitro antiproliferative activity, nitric oxide release ability, and preliminary anticancer mechanism were further evaluated. The results displayed that all the target compounds exhibited potent antiproliferative activities, with IC50 values ranging from 1.84 to 17.01μM. Besides, it was observed that in most cases, the antiproliferative activity correlated well with levels of intracellular NO release. More interestingly, preliminary mechanism studies revealed that the most potent compound 14d induced apoptosis and arrested the cell cycle at the S phase in Bel-7402 cells, which is different from parent compound oridonin. Together, the above promising results warrant the further development of oridonin/NO hybrids as potential antitumor leads.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Xu S,Wang G,Lin Y,Zhang Y,Pei L,Yao H,Hu M,Qiu Y,Huang Z,Zhang Y,Xu J

doi

10.1016/j.bmcl.2016.04.068

subject

Has Abstract

pub_date

2016-06-15 00:00:00

pages

2795-2800

issue

12

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(16)30443-7

journal_volume

26

pub_type

杂志文章

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