Synthesis and biological evaluation of novel furozan-based nitric oxide-releasing derivatives of oridonin as potential anti-tumor agents.
To search for novel nitric oxide (NO) releasing anti-tumor agents, a series of novel furoxan/oridonin hybrids were designed and synthesized. Firstly, the nitrate/nitrite levels in the cell lysates were tested by a Griess assay and the results showed that these furoxan-based NO-releasing derivatives could produce high levels of NO in vitro. Then the anti-proliferative activity of these hybrids against four human cancer cell lines was also determined, among which, 9 h exhibited the most potential anti-tumor activity with IC₅₀ values of 1.82 µM against K562, 1.81 µM against MGC-803 and 0.86 µM against Bel-7402, respectively. Preliminary structure-activity relationship was concluded based on the experimental data obtained. These results suggested that NO-donor/natural product hybrids may provide a promising approach for the discovery of novel anti-tumor agents.
Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China.
Dahong
D
Li
Lei
L
Wang
Hao
H
Cai
Yihua
Y
Zhang
Jinyi
J
Xu
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D020030:Nitric Oxide Donors / Q000737:chemistry*; D010069:Oxadiazoles / Q000737:chemistry*
C528141:1,2,5-oxadiazole 2-oxide; D000970:Antineoplastic Agents; D045786:Diterpenes, Kaurane; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; C011959:oridonin