title: Rare Streptomyces N-formyl amino-salicylamides inhibit oncogenic K-Ras.
abstract: During a search for inhibitors of oncogenic K-Ras, we detected two known and two new examples of the rare neoantimycin structure class from a liquid cultivation of Streptomyces orinoci, and reassigned/assigned structures to all based on detailed spectroscopic analysis and microscale C3 Marfey's and C3 Mosher chemical degradation/derivatization/analysis. SAR investigations inclusive of the biosynthetically related antimycins and respirantin, and synthetic benzoxazolone, documented a unique N-formyl amino-salicylamide pharmacophore as a potent inhibitor of oncogenic K-Ras.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , St. Lucia, QLD 4072, Australia.
authors.forename: Angela A
authors.initials: AA
authors.lastname: Salim
authors.forename: Kwang-Jin
authors.initials: KJ
authors.lastname: Cho
authors.forename: Lingxiao
authors.initials: L
authors.lastname: Tan
authors.forename: Michelle
authors.initials: M
authors.lastname: Quezada
authors.forename: Ernest
authors.initials: E
authors.lastname: Lacey
authors.forename: John F
authors.initials: JF
authors.lastname: Hancock
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Capon
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000187:drug effects; D047630:Depsipeptides / Q000737:chemistry; D004317:Doxorubicin / Q000494:pharmacology; D011905:Genes, ras / Q000187:drug effects*; D015394:Molecular Structure; D009930:Organic Chemicals / Q000737:chemistry; D012457:Salicylamides / Q000737:chemistry*; D013302:Streptomyces / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D047630:Depsipeptides; D009930:Organic Chemicals; D012457:Salicylamides; C081425:respirantin; C002699:neoantimycin; D004317:Doxorubicin