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Sci Rep. 2019 Jan 29;9(1):862. doi: 10.1038/s41598-018-36925-9.

Novel benzofuran derivative DK-1014 attenuates lung inflammation via blocking of MAPK/AP-1 and AKT/mTOR signaling in vitro and in vivo.

Author information

1
College of Pharmacy, Dongguk University-Seoul, Goyang, 10326, Korea.
2
Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, 34134, Korea.
3
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungju-si, Chungbuk, 28116, Korea.
4
College of Veterinary Medicine, Chonnam National University, Gwangju, 61186, Korea.
5
Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, 34134, Korea. hgjeong@cnu.ac.kr.
6
College of Pharmacy, Dongguk University-Seoul, Goyang, 10326, Korea. kaylee@dongguk.edu.

Abstract

Benzofuran derivatives have wide range of biological activities as anti-oxidant, anti-inflammatory and anticonvulsant agent. In this study, we investigated whether the novel benzofuran derivative, DK-1014 has the anti-inflammatory effects on macrophage and lung epithelial cells and anti-asthmatic effects on ovalbumin-treated mice. A series of 2-arylbenzofuran analogues were synthesized and evaluated for NO and interleukin-6 (IL-6) inhibition in LPS-stimulated Raw264.7 cells. Of these analogues, compounds 8, 22a, 22d, and 22 f (DK-1014) exhibited notable inhibitory activity with respect to IL-6 and NO production. In particular, compound DK-1014 strongly reduced IL-6, IL-8, and MMP-9 mRNA expression and IL-6, IL-8, and MCP-1 production in phorbol myristate acetate stimulated A549 cells, reduced MAPKs phosphorylation and c-fos translocation, and attenuated AKT, p70S6K and GSK phosphorylation. In vivo experiments were also performed on ovalbumin-sensitized and challenged BALB/c mice. DK-1014 reduced the airway hyperresponsiveness, inflammatory cell counts and cytokine levels (IL-4, 5, 13) in bronchial alveolar lavage fluid (BALF) and immunoglobulin E in serum, and attenuated inflammatory cell infiltration and mucus hypersecretion in lung tissue. These findings indicate that DK-1014 can protect against allergic airway inflammation through the AP-1 and AKT/mTOR pathways and could be useful source for the development of a therapeutic agent for asthma.

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