Design, synthesis, and biological characterization of tamibarotene analogs as anticancer agents.
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.
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong, China.
Yuqi
Y
Jiang
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong, China.
Xiaoyang
X
Li
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong, China.
Xue
X
Wang
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong, China.
Zhonglan
Z
Wang
College of Pharmacy, Weifang Medical University, Wei'fang, Shandong, China.
Jian
J
Zhang
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong, China. wujingde70@sdu.edu.cn.
Jingde
J
Wu
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong, China. wenfxu@163.com.
Wenfang
W
Xu
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001565:Benzoates / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D015195:Drug Design; D004355:Drug Stability; D006801:Humans; D051381:Rats; D013764:Tetrahydronaphthalenes / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001565:Benzoates; D013764:Tetrahydronaphthalenes; C061133:tamibarotene
anticancer; histone deacetylases; multitarget drugs; retinoids; tamibarotene