Synthesis and biological evaluation of nitric oxide-donating thalidomide analogues as anticancer agents.
In search of more potent anticancer agents, 15 nitric oxide (NO)-donating thalidomide analogues, 6a, 6b, 8a-8e, and 13a-13h, were designed and synthesized. Cytotoxicity of these compounds was evaluated in vitro against three human tumor cell lines (HepG2, A549, and PC-3). The results indicated that 13a-13d exhibited notable anticancer activities comparable to or stronger than that of 5-fluorouracil (5-FU). Structure-activity relationships were also discussed, based on the experimental data obtained. Generally, the cytotoxic activity of target compounds is closely related to the type of NO donors, and the length of the spacers connecting to NO donors also appears important for the bioactivities.
Center of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, P. R. China.
Tao
T
Wang
Yi-Hua
YH
Zhang
Xiang-Wen
XW
Kong
Yi-Sheng
YS
Lai
Hui
H
Ji
Yan-Ping
YP
Chen
Si-Xun
SX
Peng
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000633:toxicity; D045744:Cell Line, Tumor; D005472:Fluorouracil / Q000633:toxicity; D006801:Humans; D009569:Nitric Oxide / Q000737:chemistry*; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000633:toxicity
D000970:Antineoplastic Agents; D009569:Nitric Oxide; D013792:Thalidomide; D005472:Fluorouracil