Format

Send to

Choose Destination
Chem Biol Drug Des. 2016 Oct;88(4):542-55. doi: 10.1111/cbdd.12778. Epub 2016 Jun 1.

Design, synthesis, and biological characterization of tamibarotene analogs as anticancer agents.

Author information

1
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong, China.
2
College of Pharmacy, Weifang Medical University, Wei'fang, Shandong, China.
3
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong, China. wujingde70@sdu.edu.cn.
4
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong, China. wenfxu@163.com.

Abstract

In our efforts of developing novel compounds as potential anticancer agents, a series of tamibarotene analogs containing Zn(2+) -binding moieties were designed and developed. Biological characterization identified compound 7b as the most potent one with improved antiproliferative activities against multiple cancer cell lines, compared to parent compound tamibarotene. Further characterization also demonstrated that compound 7b exhibited moderate activities as a histone deacetylase inhibitor with IC50 of 1.8 ± 0.1 μm, thus suggesting that this could contribute to the improved antiproliferative activities of 7b. Pharmacokinetic studies revealed that compound 7b could release tamibarotene after administration and prolong the circulation time of tamibarotene, and this may also potentially contribute to the improved antiproliferative activities. Collectively, the results demonstrated that compound 7b could serve as a new lead for further development of more potent analogs as potential anticancer agents.

KEYWORDS:

anticancer; histone deacetylases; multitarget drugs; retinoids; tamibarotene

PMID:
27113097
DOI:
10.1111/cbdd.12778
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center