title: Novel natural product-based cinnamates and their thio and thiono analogs as potent inhibitors of cell adhesion molecules on human endothelial cells.
abstract: In the present study, we report the design and synthesis of novel analogs of cinnamates, thiocinnamates and thionocinnamates and evaluated the potencies of these analogs to inhibit TNF-α induced ICAM-1 expression on human endothelial cells. By using whole cell-ELISA, our screening data demonstrated that ethyl 3',4',5'-trimethoxythionocinnamate (ETMTC) is the most potent inhibitor of TNF-α induced ICAM-1, VCAM-1 and E-selectin. As functional consequences, ETMTC abrogated TNF-α induced adhesion of neutrophils to the endothelial monolayer. Structure-activity relationship studies revealed the critical role of the chain-length of the alkyl group in the alcohol moiety, number of methoxy groups in the aromatic ring of the cinnamoyl moiety and the presence of the α, β- C-C double bond in the thiocinnamates and thionocinnamates.
authors.affiliation: Molecular Immunogenetics Laboratory, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110 007, India.
authors.forename: Sarvesh
authors.initials: S
authors.lastname: Kumar
authors.forename: Brajendra K
authors.initials: BK
authors.lastname: Singh
authors.forename: Pragya
authors.initials: P
authors.lastname: Arya
authors.forename: Shashwat
authors.initials: S
authors.lastname: Malhotra
authors.forename: Rajesh
authors.initials: R
authors.lastname: Thimmulappa
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Prasad
authors.forename: Erik
authors.initials: E
authors.lastname: Van der Eycken
authors.forename: Carl E
authors.initials: CE
authors.lastname: Olsen
authors.forename: Anthony L
authors.initials: AL
authors.lastname: DePass
authors.forename: Shyam
authors.initials: S
authors.lastname: Biswal
authors.forename: Virinder S
authors.initials: VS
authors.lastname: Parmar
authors.forename: Balaram
authors.initials: B
authors.lastname: Ghosh
mesh_terms: D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002934:Cinnamates / Q000737:chemistry* / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship; D013455:Sulfur / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D001688:Biological Products; D015815:Cell Adhesion Molecules; D002934:Cinnamates; D014409:Tumor Necrosis Factor-alpha; D013455:Sulfur