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

• DOI: 10.1016/j.ejmech.2020.112079
• Publication Date: 2020-01-21T07:25:14Z
• Authors: Yingda Zang; Fangfang Lai; Junmin Fu; Chuangjun Li; Jie Ma; Chengjuan Chen; Ke Liu; Tiantai Zhang; Xiaoguang Chen; Dongming Zhang
• Keywords: Male; 0301 basic medicine; Mice, Inbred ICR; Molecular Structure; Interleukin-6; Tumor Necrosis Factor-alpha; Anti-Inflammatory Agents; Antineoplastic Agents; Phenanthrenes; Xenograft Model Antitumor Assays; 3. Good health; Mice, Inbred C57BL; Mice; Structure-Activity Relationship; 03 medical and health sciences; RAW 264.7 Cells; Drug Design; Animals; Epoxy Compounds; Female; Nitric Oxide Donors; Diterpenes; Cell Proliferation

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.