title: Structure-activity relationship of a broad-spectrum insect odorant receptor agonist.
abstract: Agonism of insect odorant receptor (OR) cation channels may represent a new strategy for the manipulation of destructive insect olfactory-driven behaviors. We have explored the chemical space around VUAA1, the first in class agonist of the obligate OR co-receptor ion channel (Orco), and describe novel compound analogues with increased potency across insect taxa. Functional analyses reveal several of these VUAA1 structural analogues display significantly greater potency as compared to the activity of the previously described active compounds in mobility-based behavioral assays on mosquito larvae.
authors.affiliation: Department of Biological Sciences, Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37235, United States.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.forename: Ian M
authors.initials: IM
authors.lastname: Romaine
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.forename: Poornima
authors.initials: P
authors.lastname: Murthi
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Jones
authors.forename: Alex G
authors.initials: AG
authors.lastname: Waterson
authors.forename: Gary A
authors.initials: GA
authors.lastname: Sulikowski
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Zwiebel
mesh_terms: D000818:Animals; D000852:Anopheles / Q000187:drug effects*; D001522:Behavior, Animal; D057809:HEK293 Cells; D006801:Humans; D007473:Ion Channels / Q000187:drug effects; D007814:Larva / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D034741:RNA, Small Interfering / Q000737:chemistry / Q000494:pharmacology; D018035:Receptors, Odorant / Q000819:agonists*; D013329:Structure-Activity Relationship; D013864:Thioglycolates / Q000138:chemical synthesis* / Q000494:pharmacology*; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D007473:Ion Channels; C572612:N-(4-ethylphenyl)-2-((4-ethyl-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)thio)acetamide; D034741:RNA, Small Interfering; D018035:Receptors, Odorant; D013864:Thioglycolates; D014230:Triazoles