Alessandra Marie Encarnacion , Nithin Pootheri , Hongyuan Yao , Zhihao Chen , Sunwoo Lee , Eunae Kim , Tae-Hoon Lee
{"title":"新型抑制剂 N-环丙基-4-((4-((4-(三氟甲基)苯基)磺酰基)哌嗪-1-基)甲基)苯甲酰胺在体外可减轻 RANKL 介导的破骨细胞分化。","authors":"Alessandra Marie Encarnacion , Nithin Pootheri , Hongyuan Yao , Zhihao Chen , Sunwoo Lee , Eunae Kim , Tae-Hoon Lee","doi":"10.1016/j.bmcl.2024.129884","DOIUrl":null,"url":null,"abstract":"<div><p>Both cyclopropyl amide and piperazine sulfonamide functional groups are known for their various biological properties used for drug development. Herein, we synthesized nine new derivatives with different substituent groups incorporating these moieties and screened them for their anti-osteoclast differentiation activity. After analyzing the structure–activity relationship (SAR), the inhibitory effect against osteoclastogenesis was determined to be dependent on the lipophilicity of the compound. Derivative <strong>5b</strong> emerged as the most effective dose-dependent inhibitor after TRAP staining with an IC<sub>50</sub> of 0.64 µM against RANKL-induced osteoclast cells. <strong>5b</strong> was also able to suppress F-acting ring formation and bone resorption activity of osteoclasts in vitro. Finally, well-acknowledged gene and protein osteoclast-specific marker expression levels were decreased after <strong>5b</strong> administration on primary murine osteoclast cells.</p></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Novel inhibitor N-cyclopropyl-4-((4-((4-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)benzamide attenuates RANKL-mediated osteoclast differentiation in vitro\",\"authors\":\"Alessandra Marie Encarnacion , Nithin Pootheri , Hongyuan Yao , Zhihao Chen , Sunwoo Lee , Eunae Kim , Tae-Hoon Lee\",\"doi\":\"10.1016/j.bmcl.2024.129884\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Both cyclopropyl amide and piperazine sulfonamide functional groups are known for their various biological properties used for drug development. Herein, we synthesized nine new derivatives with different substituent groups incorporating these moieties and screened them for their anti-osteoclast differentiation activity. After analyzing the structure–activity relationship (SAR), the inhibitory effect against osteoclastogenesis was determined to be dependent on the lipophilicity of the compound. Derivative <strong>5b</strong> emerged as the most effective dose-dependent inhibitor after TRAP staining with an IC<sub>50</sub> of 0.64 µM against RANKL-induced osteoclast cells. <strong>5b</strong> was also able to suppress F-acting ring formation and bone resorption activity of osteoclasts in vitro. Finally, well-acknowledged gene and protein osteoclast-specific marker expression levels were decreased after <strong>5b</strong> administration on primary murine osteoclast cells.</p></div>\",\"PeriodicalId\":256,\"journal\":{\"name\":\"Bioorganic & Medicinal Chemistry Letters\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-07-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bioorganic & Medicinal Chemistry Letters\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0960894X24002865\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic & Medicinal Chemistry Letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0960894X24002865","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Novel inhibitor N-cyclopropyl-4-((4-((4-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)benzamide attenuates RANKL-mediated osteoclast differentiation in vitro
Both cyclopropyl amide and piperazine sulfonamide functional groups are known for their various biological properties used for drug development. Herein, we synthesized nine new derivatives with different substituent groups incorporating these moieties and screened them for their anti-osteoclast differentiation activity. After analyzing the structure–activity relationship (SAR), the inhibitory effect against osteoclastogenesis was determined to be dependent on the lipophilicity of the compound. Derivative 5b emerged as the most effective dose-dependent inhibitor after TRAP staining with an IC50 of 0.64 µM against RANKL-induced osteoclast cells. 5b was also able to suppress F-acting ring formation and bone resorption activity of osteoclasts in vitro. Finally, well-acknowledged gene and protein osteoclast-specific marker expression levels were decreased after 5b administration on primary murine osteoclast cells.
期刊介绍:
Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.