title: Tubulin modulating antifungal and antiproliferative pyrazinone derivatives.
abstract: A novel class of synthetic tubulin polymerization disruptors, based on a substituted pyrazin-2-one core, has been discovered. These molecules have proven to be potent broad spectrum fungicides, with activity on agriculturally important ascomycete and basidiomycete pathogens. They have also been found to be particularly potent against human rhabdomyosarcoma cells. Using an efficient synthetic route, the agricultural and medicinal activity was explored.
authors.affiliation: DuPont Crop Protection, Discovery Chemistry, 1090 Elkton Road, Newark, DE 19714, USA. Electronic address: andrew.e.taggi@dupont.com.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Taggi
authors.affiliation: DuPont Crop Protection, Discovery Chemistry, 1090 Elkton Road, Newark, DE 19714, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Stevenson
authors.affiliation: DuPont Crop Protection, Discovery Chemistry, 1090 Elkton Road, Newark, DE 19714, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Bereznak
authors.affiliation: DuPont Crop Protection, Discovery Chemistry, 1090 Elkton Road, Newark, DE 19714, USA.
authors.forename: Paula L
authors.initials: PL
authors.lastname: Sharpe
authors.affiliation: DuPont Crop Protection, Chemical Genomics, 1090 Elkton Road, Newark, DE 19714, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Gutteridge
authors.affiliation: DuPont Crop Protection, Discovery Biology, 1090 Elkton Road, Newark, DE 19714, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Forman
authors.affiliation: DuPont Crop Protection, Discovery Chemistry, 1090 Elkton Road, Newark, DE 19714, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Bisaha
authors.affiliation: DuPont Crop Protection, Chemical Genomics, 1090 Elkton Road, Newark, DE 19714, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cordova
authors.affiliation: DuPont Crop Protection, Discovery Biology, 1090 Elkton Road, Newark, DE 19714, USA.
authors.forename: Martina
authors.initials: M
authors.lastname: Crompton
authors.affiliation: DuPont Crop Protection, Discovery Chemistry, 1090 Elkton Road, Newark, DE 19714, USA.
authors.forename: Lora
authors.initials: L
authors.lastname: Geist
authors.affiliation: DuPont Crop Protection, Discovery Chemistry, 1090 Elkton Road, Newark, DE 19714, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Kovacs
authors.affiliation: DuPont Crop Protection, Discovery Chemistry, 1090 Elkton Road, Newark, DE 19714, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Marshall
authors.affiliation: DuPont Crop Protection, Discovery Chemistry, 1090 Elkton Road, Newark, DE 19714, USA.
authors.forename: Ritesh
authors.initials: R
authors.lastname: Sheth
authors.affiliation: DuPont Crop Protection, Discovery Chemistry, 1090 Elkton Road, Newark, DE 19714, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Stavis
authors.affiliation: DuPont Crop Protection, Discovery Chemistry, 1090 Elkton Road, Newark, DE 19714, USA.
authors.forename: Chi-Ping
authors.initials: CP
authors.lastname: Tseng
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005659:Fungicides, Industrial / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011719:Pyrazines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D005659:Fungicides, Industrial; D011719:Pyrazines; D014404:Tubulin; D050257:Tubulin Modulators
keywords: Agriculture; Cell line; Fungicide; Pathogen; Synthesis; Tubulin