2. Academic Validation
  3. Synthesis and evaluation of butein derivatives for in vitro and in vivo inflammatory response suppression in lymphedema

Synthesis and evaluation of butein derivatives for in vitro and in vivo inflammatory response suppression in lymphedema

  • Eur J Med Chem. 2020 Jul 1;197:112280. doi: 10.1016/j.ejmech.2020.112280.
Kangsan Roh 1,  Jung-Hun Lee 2,  Hee Kang 3,  Kye Won Park 4,  Youngju Song 5,  Sukchan Lee 6,  Jin-Mo Ku 7
Affiliations

Affiliations

  • 1 Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
  • 2 Bio-Center, Gyeonggido Business & Science Accelerator, 147 Gwanggyo-ro, Suwon, 16229, Republic of Korea.
  • 3 Humanitas College, Kyung Hee University, Yongin, 17104, Republic of Korea.
  • 4 Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
  • 5 Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.
  • 6 Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea. Electronic address: [email protected].
  • 7 Bio-Center, Gyeonggido Business & Science Accelerator, 147 Gwanggyo-ro, Suwon, 16229, Republic of Korea. Electronic address: [email protected].
PMID: 32361286 DOI: 10.1016/j.ejmech.2020.112280
Abstract

Herein, we demonstrate that butein (1) can prevent swelling in a murine lymphedema model by suppressing tumor necrosis factor α (TNF-α) production. Butein derivatives were synthesized and evaluated to identify compounds with in vitro anti-inflammatory activity. Among them, 20 μM of compounds 7j, 7m, and 14a showed 50% suppression of TNF-α production in mouse peritoneal macrophages after lipopolysaccharide stimulation. Compound 14a, exhibited the strongest potency with an in vitro IC50 of 14.6 μM and suppressed limb volume by 70% in a murine lymphedema model. The prodrug strategy enabled a six-fold increase in kinetic solubility of compound 1 and five-fold higher levels of active metabolite in the blood for compound 14a via oral administration in the pharmacokinetics study. We suggest that the compound 14a could be developed as a potential therapeutic agent targeting anti-inflammatory activity to alleviate lymphedema progression.

Keywords

Acquired lymphedema; Chalcones; Inflammation; Therapeutic agent.

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