2. Academic Validation
  3. Improved synthesis, molecular modeling and anti-inflammatory activity of new fluorinated dihydrofurano-naphthoquinone compounds

Improved synthesis, molecular modeling and anti-inflammatory activity of new fluorinated dihydrofurano-naphthoquinone compounds

  • Bioorg Med Chem Lett. 2024 Mar 22:104:129714. doi: 10.1016/j.bmcl.2024.129714.
Ha Thanh Nguyen 1,  Hai Pham-The 2,  Anh Nguyen Tuan 3,  Ha Nguyen Thi Thu 4,  Tuyet Anh Dang Thi 4,  Giang Le-Nhat-Thuy 4,  Phuong Hoang Thi 3,  Quynh Giang Nguyen Thi 3,  Tuyen Van Nguyen 4
Affiliations

Affiliations

  • 1 Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam; Graduate University of Science and Technology, VAST, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam. Electronic address: [email protected].
  • 2 Department of Life Science, University of Science and Technology of Hanoi (USTH), VAST, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam.
  • 3 Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam.
  • 4 Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam; Graduate University of Science and Technology, VAST, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam.
PMID: 38522589 DOI: 10.1016/j.bmcl.2024.129714
Abstract

A series of new fluorinated dihydrofurano-napthoquinone compounds were sucessfully synthesized in good yields using microwave-assisted multi-component reactions of 2-hydroxy-1,4-naphthoquinone, fluorinated aromatic aldehydes, and pyridinium bromide. The products were fully characterized using spectroscopic techniques and evaluated for their anti-inflammatory activity using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Among 12 new compounds, compounds 8b, 8d, and 8e showed high potent NO inhibitory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells with IC50 values ranging from 1.54 to 3.92 µM. The levels of pro-inflammatory cytokines IL-1β and IL-6 in LPS-stimulated RAW264.7 macrophages were remarkably decreased after the application of 8b, 8d, 8e and 8k. Molecular docking simulations revealed structure-activity relationships of 8b, 8d, and 8e toward NO Synthase, cyclooxygenase (COX-2 over COX-1), and prostaglandin E synthase-1 (mPGES-1). Further physicochemical and pharmacokinetic computations also demonstrated the drug-like characteristics of synthesized compounds. These findings demonstrated the importance of fluorinated dihydrofurano-napthoquinone moieties in the development of potential anti-inflammatory agents.

Keywords

Anti-inflammation; Fluorinated dihydrofurano-napthoquinones; Molecular docking simulation; Multi-component reaction; inhibitor of NO production and pro-inflammatory cytokines.

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