Synthesis and antitumor activity of ATB-429 derivatives containing a nitric oxide-releasing moiety

Chunlan Wang; Guimin Xia; Xiujun Liu; Rui Zhang; Yun Chai; Jun Zhang; Xiaoning Li; Yang Yang; Juxian Wang; Mingliang Liu

doi:10.1016/j.bmcl.2016.03.012

Synthesis and antitumor activity of ATB-429 derivatives containing a nitric oxide-releasing moiety

Bioorg Med Chem Lett. 2016 May 1;26(9):2355-9. doi: 10.1016/j.bmcl.2016.03.012. Epub 2016 Mar 4.

Authors

Chunlan Wang¹, Guimin Xia¹, Xiujun Liu², Rui Zhang¹, Yun Chai¹, Jun Zhang³, Xiaoning Li¹, Yang Yang¹, Juxian Wang¹, Mingliang Liu⁴

Affiliations

¹ Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
² Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: [email protected].
³ Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Zhejiang Starry Pharmaceutical Co. Ltd, Xianju 317300, China.
⁴ Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: [email protected].

PMID: 26995527
DOI: 10.1016/j.bmcl.2016.03.012

Abstract

A series of novel ATB-429 (an anti-inflammatory candidate) derivatives containing a nitric oxide (NO)-releasing moiety were designed, synthesized and evaluated for their in vitro activity against six human cancer cell lines. Our results reveal that phenylsulfonylfuroxan-based derivatives have considerable antitumor activity, and compounds 7-9 (IC50s: 0.256-3.024 μM) against HT-29 and PANC-1, 8a,b (IC50s: 2.677-3.051 μM) against MCF-7 and 8a (IC50: 1.270 μM) against DU145 are more active than Vandetanib (IC50s: 1.925-4.107 μM).

Keywords: ATB-429 derivatives; Antitumor activity; Nitric oxide; Synthesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Disulfides / chemistry*
Drug Screening Assays, Antitumor
Humans
Mesalamine / chemistry*
Nitric Oxide / chemistry*

Substances

5-amino-2-hydroxybenzoic acid 4-(5-thioxo-5H-(1,2)dithiol-3yl)phenyl ester
Antineoplastic Agents
Disulfides
Nitric Oxide
Mesalamine