title: Arylalkyl ketones, benzophenones, desoxybenzoins and chalcones inhibit TNF-α induced expression of ICAM-1: structure-activity analysis.
abstract: The interaction between leukocytes and the vascular endothelial cells (EC) via cellular adhesion molecules plays an important role in the pathogenesis of various inflammatory and autoimmune diseases. Small molecules that block these interactions have been targeted as potential therapeutic agents against acute and chronic inflammatory diseases. In an effort to identify potent intercellular cell adhesion molecule-1 (ICAM-1) inhibitors, a large number of arylalkyl ketones, benzophenones, desoxybenzoins and chalcones and their analogs (54 in total) have been synthesized and screened for their ICAM-1 inhibitory activity. The structure-activity relationship studies of these compounds identified three potent chalcone derivatives and also demonstrated the possible mechanism for their ICAM-1 inhibitory activities. The most active compound was found to be 79.
authors.affiliation: Laboratory of Immunogenetics, CSIR - Institute of Genomics and Integrative Biology, Delhi University Campus, Delhi, India.
authors.forename: Sarvesh
authors.initials: S
authors.lastname: Kumar
authors.forename: Chandra Shekhar
authors.initials: CS
authors.lastname: Reddy L
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Kumar
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.forename: Brajendra K
authors.initials: BK
authors.lastname: Singh
authors.forename: Vineet
authors.initials: V
authors.lastname: Kumar
authors.forename: Shashwat
authors.initials: S
authors.lastname: Malhotra
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Pandey
authors.forename: Rajni
authors.initials: R
authors.lastname: Jain
authors.forename: Rajesh
authors.initials: R
authors.lastname: Thimmulappa
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Sharma
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Prasad
authors.forename: Shyam
authors.initials: S
authors.lastname: Biswal
authors.forename: Erik
authors.initials: E
authors.lastname: Van der Eycken
authors.forename: Anthony L
authors.initials: AL
authors.lastname: DePass
authors.forename: Sanjay V
authors.initials: SV
authors.lastname: Malhotra
authors.forename: Balaram
authors.initials: B
authors.lastname: Ghosh
authors.forename: Virinder S
authors.initials: VS
authors.lastname: Parmar
mesh_terms: D001573:Benzoin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001577:Benzophenones / Q000494:pharmacology*; D002478:Cells, Cultured; D047188:Chalcones / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007659:Ketones / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D001577:Benzophenones; D047188:Chalcones; D007659:Ketones; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D001573:Benzoin