title: N-hydroxyl derivatives of guanidine based drugs as enzymatic NO donors.
abstract: Recent research suggests that NO may play a role in the physiological effects of some guanidine-containing drugs. In this report, three guanidine-containing drugs (guanadrel, guanoxan, and guanethidine) together with their N-hydroxyl derivatives were synthesized and their NO-releasing abilities catalyzed by nitric oxide synthases (NOSs) and horseradish peroxidase were evaluated. The guanidine containing compounds could not release NO in the presence of NOS or peroxidase. The corresponding N-hydroxyl compounds exhibited weak NO-releasing ability under the catalyzed of NOS and good NO-releasing ability under the oxidation by horseradish peroxidase in the presence of H(2)O(2). These compounds also displayed vasodilatory activity.
authors.affiliation: Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.
authors.forename: M
authors.initials: M
authors.lastname: Xian
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: X
authors.initials: X
authors.lastname: Tang
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: Z
authors.initials: Z
authors.lastname: Zheng
authors.forename: J J
authors.initials: JJ
authors.lastname: Galligan
authors.forename: D L
authors.initials: DL
authors.lastname: Kreulen
authors.forename: P G
authors.initials: PG
authors.lastname: Wang
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism; D004146:Dioxanes / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D019791:Guanidine / Q000737:chemistry*; D006146:Guanidines / Q000737:chemistry* / Q000494:pharmacology*; D006168:Guinea Pigs; D006735:Horseradish Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D020030:Nitric Oxide Donors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D004146:Dioxanes; D006146:Guanidines; C442395:N-hydroxyguanoxan; D020030:Nitric Oxide Donors; D009573:Nitrites; D014665:Vasodilator Agents; D001120:Arginine; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D019001:Nitric Oxide Synthase; D019791:Guanidine