当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Design, synthesis and anticancer properties of novel oxa/azaspiro[4,5]trienones as potent apoptosis inducers through mitochondrial disruption.

Design, synthesis and anticancer properties of novel oxa/azaspiro[4,5]trienones as potent apoptosis inducers through mitochondrial disruption.

Abstract：

:A series of twenty seven oxa/azaspiro[4,5]trienone derivatives were synthesized and their anticancer properties have been explored. GI50 values of all these compounds were evaluated against four types of human cancer cell lines, i.e. MCF-7 (breast), DU-145 (prostate), A549 (lung) and HepG2 (liver). Five compounds of the series exhibited good anticancer potential against MCF-7 with GI50 values less than 2 μM. Detailed biological studies of the two representative compounds 9b and 9e revealed that they arrest cell cycle in G0/G1 phase and induce mitochondria mediated apoptosis, that was further confirmed by measurement of mitochondrial membrane potential (ΔΨm), intracellular ROS generation, caspase 9 activity and Annexin V-FITC assay. Furthermore, western blot analysis suggested that these compounds up-regulate the levels of p53, p21, p27 and Bax, and down-regulate the level of Bcl-2 confirming the apoptosis inducing properties.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Yugandhar D,Nayak VL,Archana S,Shekar KC,Srivastava AK

doi

10.1016/j.ejmech.2015.06.050

subject

Has Abstract

pub_date

2015-08-28 00:00:00

pages

348-57

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(15)30129-X

journal_volume

101

pub_type

杂志文章

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