Design and synthesis of cantharidin derivative DCZ5418 as a TRIP13 inhibitor with anti-multiple myeloma activity in vitro and in vivo
文献类型：期刊论文
| 作者 | Dong, Sanfeng2,4,6; Hu, Ke5; Shi, Yulong1,6; Wang, Guanli5; Yu, Dandan3; Zhao, Yitian4,6; Zhang, Hui5; Wang, Yingcong3; Sun, Haiguo1,6; Xu, Zhijian1,6
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
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| 出版日期 | 2024-01-15 |
| 卷号 | 98页码:7 |
| 关键词 | Multiple myeloma TRIP13 inhibitor Cantharidin DCZ5418 DCZ0415 |
| ISSN号 | 0960-894X |
| DOI | 10.1016/j.bmcl.2023.129590 |
| 通讯作者 | Li, Bo(boli@simm.ac.cn) ; Shi, Jumei(shijumei@tongji.edu.cn) ; Zhu, Weiliang(wlzhu@simm.ac.cn) |
| 英文摘要 | Natural product cantharidin can inhibit multiple myeloma cell growth in vitro, while serious adverse effects limited its clinical application. Therefore, the structural modification of cantharidin is needed. Herein, inspired by the structural similarity of the aliphatic endocyclic moiety in cantharidin and TRIP13 inhibitor DCZ0415, we designed and synthesized DCZ5418 and its nineteen derivatives. The molecular docking study indicated that DCZ5418 had a similar binding mode to TRIP13 protein as DCZ0415 while with a stronger docking score. Moreover, the bioassay studies of the MM-cells viability inhibition, TRIP13 protein binding affinity and enzyme inhibiting activity showed that DCZ5418 had good anti-MM activity in vitro and definite interaction with TRIP13 protein. The acute toxicity test of DCZ5418 showed less toxicity in vivo than cantharidin. Furthermore, DCZ5418 showed good anti-MM effects in vivo with a lower dose administration than DCZ0415 (15 mg/kg vs 25 mg/kg) on the tumor xenograft models. Thus, we obtained a new TRIP13 inhibitor DCZ5418 with improved safety and good activity in vivo, which provides a new example of lead optimization by using the structural fragments of natural products. |
| 资助项目 | National Natural Science Foundation of China[22077131] ; National Natural Science Foundation of China[82170200] ; National Natural Science Foundation of China[22277129] ; National Key Research and Development Program of China[2022YFA1004304] ; Chinese Pharmaceutical Association-Yiling Biopharmaceutical Innovation Project[CPAYLJ201908] ; State Key Laboratory of Natural and Biomimetic Drugs[K202108] ; Natural Science Foundation of Shanghai, China[19ZR1467800] |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001137380500001 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/308520]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Li, Bo; Shi, Jumei; Zhu, Weiliang |
| 作者单位 | 1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 2.Fudan Univ, Sch Pharm, 826 Zhangheng Rd, Shanghai 201203, Peoples R China 3.Tongji Univ, Shanghai Peoples Hosp 10, Dept Hematol, Sch Med, Shanghai 200072, Peoples R China 4.Shanghai Univ Tradit Chinese Med, 1200 Cailun Rd, Shanghai 201203, Peoples R China 5.Tongji Univ, Shanghai East Hosp, Dept Hematol, Sch Med, Shanghai 200120, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 7.Peking Univ, State Key Lab Nat & Biomimet Drugs, 38 Xue Yuan Rd, Beijing 100191, Peoples R China |
| 推荐引用方式 GB/T 7714 | Dong, Sanfeng,Hu, Ke,Shi, Yulong,et al. Design and synthesis of cantharidin derivative DCZ5418 as a TRIP13 inhibitor with anti-multiple myeloma activity in vitro and in vivo[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2024,98:7. |
| APA | Dong, Sanfeng.,Hu, Ke.,Shi, Yulong.,Wang, Guanli.,Yu, Dandan.,...&Zhu, Weiliang.(2024).Design and synthesis of cantharidin derivative DCZ5418 as a TRIP13 inhibitor with anti-multiple myeloma activity in vitro and in vivo.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,98,7. |
| MLA | Dong, Sanfeng,et al."Design and synthesis of cantharidin derivative DCZ5418 as a TRIP13 inhibitor with anti-multiple myeloma activity in vitro and in vivo".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 98(2024):7. |
入库方式： OAI收割
来源：上海药物研究所
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