Novel nitric oxide-releasing derivatives of triptolide as antitumor and anti-inflammatory agents: Design, synthesis, biological evaluation, and nitric oxide release studies

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 (LD50 = 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. [Display omitted] •We synthesized analogues of triptolide, an isolate from the thunder god vine.•Compound 33 showed good antiproliferative activity and NO releasing ability.•Compound 33 was more than 160-times less toxic than triptolide.•Compound 33 inhibited the growth of melanoma at a low dose (0.3 mg/kg).•Compound 33 showed strong anti-inflammatory activity in vitro and in vivo.