State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People's Republic of China.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People's Republic of China.
Eur J Med Chem. 2020 Mar 15;190:112079. doi: 10.1016/j.ejmech.2020.112079. Epub 2020 Jan 21.
A series of novel triptolide/furoxans hybrids were designed and synthesized as analogues of triptolide, which is a naturally derived compound isolated from the thunder god vine (Tripterygium wilfordii Hook. F). Some of these synthesized compounds exhibited antiproliferative activities in the nanomolar range. Among them, compound 33 exhibited both good antiproliferative activity and NO-releasing ability and the acute toxicity of compound 33 decreased more than 160 times (LD = 160.9 mg/kg) than triptolide. Moreover, compound 33 significantly inhibited the growth of melanoma at a low dose (0.3 mg/kg) and showed strong anti-inflammatory activity in vitro and in vivo. These results indicate that compound 33 could be a promising candidate for further study.
一系列新型雷公藤内酯/呋咱类化合物被设计并合成为雷公藤内酯的类似物，雷公藤内酯是一种从雷公藤（Tripterygium wilfordii Hook. F）中分离得到的天然化合物。其中一些合成的化合物在纳摩尔范围内表现出抗增殖活性。在这些化合物中，化合物 33 既具有良好的抗增殖活性又具有释放 NO 的能力，并且化合物 33 的急性毒性比雷公藤内酯降低了 160 多倍（LD = 160.9 mg/kg）。此外，化合物 33 在低剂量（0.3 mg/kg）下显著抑制黑色素瘤的生长，并在体外和体内表现出很强的抗炎活性。这些结果表明，化合物 33 可能是进一步研究的有前途的候选物。
