2. Academic Validation
  3. Novel inhibitor N-cyclopropyl-4-((4-((4-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)benzamide attenuates RANKL-mediated osteoclast differentiation in vitro

Novel inhibitor N-cyclopropyl-4-((4-((4-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)benzamide attenuates RANKL-mediated osteoclast differentiation in vitro

  • Bioorg Med Chem Lett. 2024 Sep 15:110:129884. doi: 10.1016/j.bmcl.2024.129884.
Alessandra Marie Encarnacion 1,  Nithin Pootheri 2,  Hongyuan Yao 1,  Zhihao Chen 3,  Sunwoo Lee 2,  Eunae Kim 4,  Tae-Hoon Lee 5
Affiliations

Affiliations

  • 1 Interdisciplinary Department of Biomedical Engineering, Chonnam National University, Gwangju 61186, South Korea.
  • 2 Department of Chemistry, Chonnam National University, Gwangju 61186, South Korea.
  • 3 Department of Oral Biochemistry, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju 61186, South Korea.
  • 4 College of Pharmacy, Chosun University, Gwangju 61452, South Korea; Host-directed Antiviral Research Center, College of Veterinary Medicine, Chonnam National University, Gwangju, 61186, Republic of Korea. Electronic address: eunaekim@chosun.ac.kr.
  • 5 Interdisciplinary Department of Biomedical Engineering, Chonnam National University, Gwangju 61186, South Korea; Department of Oral Biochemistry, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju 61186, South Korea. Electronic address: thlee83@jnu.ac.kr.
PMID: 38996939 DOI: 10.1016/j.bmcl.2024.129884
Abstract

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.

Keywords

Cyclopropyl amide; Inhibitor; Osteoclasts; Piperazine sulfonamide; RANKL.

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