Novel antileukemic agents derived from tamibarotene and nitric oxide donors.
A series of novel nitric oxide-releasing tamibarotene derivatives were synthesized by coupling nitric oxide (NO) donors with tamibarotene via various spacers, and were evaluated for their antiproliferative activities against human leukemic HL-60, NB4 and K562 cell lines in vitro. The test results showed that three compounds (7g, 9a and 9e) exhibited more potent antileukemic activity than the control tamibarotene. Furthermore, the preliminary structure-activity analysis revealed that amino acids serving as spacers could bring about significantly improved biological activities of NO donor hybrids. These interesting results could provide new insights into the development of NO-based antileukemic agents.
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong, China.
Haiyong
H
Bian
Jinhong
J
Feng
Minyong
M
Li
Wenfang
W
Xu
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001565:Benzoates / Q000737:chemistry* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007938:Leukemia / Q000188:drug therapy; D015394:Molecular Structure; D020030:Nitric Oxide Donors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000737:chemistry* / Q000494:pharmacology
D000970:Antineoplastic Agents; D001565:Benzoates; D020030:Nitric Oxide Donors; D013764:Tetrahydronaphthalenes; C061133:tamibarotene