Novel Quinoxaline-2-Carbonitrile-1,4-Dioxide Derivatives Suppress HIF1α Activity and Circumvent MDR in Cancer Cells.

Abstract:

:A series of 3-aryl/hetarylquinoxaline-2-carbonitrile-1,4-dioxides was synthesized and evaluated against breast cancer cell lines in normoxia and hypoxia. Selected compounds in this series demonstrated better cytotoxicity and comparable hypoxia selectivity than tirapazamine. In contrast to Dox, quinoxaline-1,4-dioxides showed potent cytotoxicity against different MDR cells. Compound 2g inhibits of cancer cell growth through p53-independent mechanisms. Our results showed that compound 2g sensitized MCF-7 cells to metformin in hypoxia. Treatment with 2g results in the increase of ROS accumulation in cancer cells. Compound 2g can be considered as the lead compound for further anticancer drug design, evaluation, and development of new potent antitumor agents.

journal_name

Cancer Invest

journal_title

Cancer investigation

authors

Scherbakov AM,Borunov AM,Buravchenko GI,Andreeva OE,Kudryavtsev IA,Dezhenkova LG,Shchekotikhin AE

doi

10.1080/07357907.2018.1453072

subject

Has Abstract

pub_date

2018-03-16 00:00:00

pages

199-209

issue

3

eissn

0735-7907

issn

1532-4192

journal_volume

36

pub_type

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