Synthesis and Biological Evaluation of C-17-Amino-Substituted Pyrazole-Fused Betulinic Acid Derivatives as Novel Agents for Osteoarthritis Treatment
文献类型：期刊论文
| 作者 | Wang, Jie1,2; Wei, Wenhui2,3; Zhang, Xiaofei1; Cao, Shiqi2,3; Hu, Bintao2,4; Ye, Yang2,4 ; Jiang, Min5; Wang, Tianqi5; Zuo, Jianping2,3; He, Shijun2,3
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2021-09-23 |
| 卷号 | 64期号:18页码:13676-13692 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.1c01019 |
| 文献子类 | Article |
| 英文摘要 | A series of pyrazole-fused betulinic acid (BA) derivatives were designed and synthesized by replacing the carboxyl group at C-17 with aliphatic amine, amide, and urea groups. The suppressive effects of the compounds on osteoclast (OC) formation and inflammatory cytokine production were evaluated on murine macrophages, RAW264.7 cells, conditioned with receptor activator for nuclear factor-kappa B ligand (RANKL)/macrophage colony stimulating factor (M-CSF) or lipopolysaccharide (LPS), respectively. Results showed that, compared with betulinic acid, most of these compounds exhibited significant improvements in inhibitory potency. Compound 25 exhibited distinguished activities on inhibiting OC differentiation with an IC50 value of 1.86 mu M. Meanwhile, compound 25, displaying the most promising suppression on IL-1 beta secretion from RAW264.7 cells, was further found to possess therapeutic effects in the sodium monoiodoacetate (MIA)-induced osteoarthritis rat model. Dose-dependent benefits were observed in MIA-elicited rats with ameliorated joint pain as well as decreased cartilage damage and bone changes after compound 25 treatment. |
| WOS关键词 | OSTEOCLAST DIFFERENTIATION ; CARTILAGE HISTOPATHOLOGY ; DRUG DISCOVERY ; ANIMAL-MODELS ; IN-VITRO ; PAIN ; INFLAMMATION ; PRINCIPLES ; SOLUBILITY ; MECHANISM |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000701513400032 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309369]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zuo, Jianping; He, Shijun; Yang, Chunhao |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Lab Immunopharmacol, Shanghai 201203, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Nat Prod Chem Dept, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 5.Shanghai Jiao Tong Univ, Shanghai Ruijin Hosp, Shanghai Inst Traumatol & Orthopaed, Shanghai Key Lab Bone & Joint Dis,Sch Med, Shanghai 200025, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Jie,Wei, Wenhui,Zhang, Xiaofei,et al. Synthesis and Biological Evaluation of C-17-Amino-Substituted Pyrazole-Fused Betulinic Acid Derivatives as Novel Agents for Osteoarthritis Treatment[J]. JOURNAL OF MEDICINAL CHEMISTRY,2021,64(18):13676-13692. |
| APA | Wang, Jie.,Wei, Wenhui.,Zhang, Xiaofei.,Cao, Shiqi.,Hu, Bintao.,...&Yang, Chunhao.(2021).Synthesis and Biological Evaluation of C-17-Amino-Substituted Pyrazole-Fused Betulinic Acid Derivatives as Novel Agents for Osteoarthritis Treatment.JOURNAL OF MEDICINAL CHEMISTRY,64(18),13676-13692. |
| MLA | Wang, Jie,et al."Synthesis and Biological Evaluation of C-17-Amino-Substituted Pyrazole-Fused Betulinic Acid Derivatives as Novel Agents for Osteoarthritis Treatment".JOURNAL OF MEDICINAL CHEMISTRY 64.18(2021):13676-13692. |
入库方式： OAI收割
来源：上海药物研究所
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