title: Design, synthesis, and structure-activity relationship study of halogen containing 2-benzylidene-1-indanone derivatives for inhibition of LPS-stimulated ROS production in RAW 264.7 macrophages.
abstract: As a continuous effort to discover new potential anti-inflammatory agents, we systematically designed and synthesized sixty-one 2-benzylidene-1-indanone derivatives with structural modification of chalcone, and evaluated their inhibitory activity on LPS-stimulated ROS production in RAW 264.7 macrophages. Systematic structure-activity relationship study revealed that hydroxyl group in C-5, C-6, or C-7 position of indanone moiety, and ortho-, meta-, or para-fluorine, trifluoromethyl, trifluoromethoxy, and bromine functionalities in phenyl ring are important for inhibition of ROS production in LPS-stimulated RAW 264.7 macrophages. Among all the tested compounds, 6-hydroxy-2-(2-(trifluoromethoxy) benzylidene)-2,3-dihydro-1H-inden-1-one (compound 44) showed the strongest inhibitory activity of ROS production. Further studies on the mode of action revealed that compound 44 potently suppressed LPS-stimulated ROS production via modulation of NADPH oxidase. The findings of this work could be useful to design 2-benzylidene-indanone based lead compounds as novel anti-inflammatory agents.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Aarajana
authors.initials: A
authors.lastname: Shrestha
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Hye
authors.initials: H
authors.lastname: Jin Oh
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Nirmala Tilija
authors.initials: NT
authors.lastname: Pun
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Til Bahadur Thapa
authors.initials: TBT
authors.lastname: Magar
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Bist
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Hongseok
authors.initials: H
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. Electronic address: parkp@yu.ac.kr.
authors.forename: Pil-Hoon
authors.initials: PH
authors.lastname: Park
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. Electronic address: eslee@yu.ac.kr.
authors.forename: Eung-Seok
authors.initials: ES
authors.lastname: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology*; D001597:Benzylidene Compounds / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D054879:Halogenation; D007189:Indans / Q000737:chemistry* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D000067996:RAW 264.7 Cells; D017382:Reactive Oxygen Species / Q000276:immunology*; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D001597:Benzylidene Compounds; D007189:Indans; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; C013352:indacrinone
keywords: Anti-inflammatory agents; Halogen containing 2-benzylidene-1-indanone; Inhibition of ROS production; RAW 264.7 macrophages; Structure-activity relationship