FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2024401413> ?p ?o ?g. }

• W2024401413 endingPage "516" @default.
• W2024401413 startingPage "510" @default.
• W2024401413 abstract "The induction of a calcium‐independent isoform of nitric oxide (NO) synthase (iNOS) and a subsequent enhanced formation of NO has been implicated in the pathophysiology of a variety of diseases including inflammation and circulatory shock. Here we demonstrate that the S‐substituted isothioureas, S‐methylisothiourea (SMT), S‐(2‐aminoethyl)isothiourea (aminoethyl‐TU), S‐ethylisothiourea (ethyl‐TU) and S‐isopropylisothiourea (isopropyl‐TU) potently inhibit iNOS activity in J774.2 macrophages activated with bacterial endotoxin with EC 50 values 8–24 times lower than that of N G ‐methyl‐ l ‐arginine (MeArg) and 200‐times lower than that of N G ‐nitro‐ l ‐arginine ( l ‐NO 2 Arg). The inhibition of iNOS activity by these S‐substituted isothioureas is dose‐dependently prevented by excess of l ‐arginine suggesting that these isothioureas are competitive inhibitors of iNOS at the l ‐arginine binding site. Ethyl‐TU and isopropyl‐TU are 4–6 times more potent than MeArg in inhibiting the constitutive NOS activity in homogenates of bovine aortic endothelial cells (eNOS) and are more potent pressor agents than MeArg in the anaesthetized rat. SMT is equipotent with MeArg, whereas aminoethyl‐TU is 6‐times less potent in inhibiting eNOS activity in vitro . Both SMT and aminoethyl‐TU, however, elicit only weak pressor responses (approximately 15mmHg at 10 mg kg −1 , i.v.) in vivo . A comparison of the potencies of ethyl‐, iso‐propyl‐, n‐propyl‐, t‐butyl‐ and n‐butyl‐isothioureas on iNOS activity shows that the inhibitory activity of S‐substituted isothioureas declines sharply if the side chain exceeds 2 carbon atoms in length. Similarly, substitution of the ethylene side chain of ethyl‐TU also results in a diminished potency. Substitution of either one or both nitrogens of SMT with either amino or alkyl groups also substantially reduces its NOS inhibitory potency. In conclusion, isothioureas represent a new class of NOS inhibitors which includes the most potent inhibitors of iNOS activity reported to date. Some members of this class (ethyl‐TU and isopropyl‐TU) are potent inhibitors of eNOS and iNOS with little selectivity towards either isoform, while others (SMT and aminoethyl‐TU) are relatively selective inhibitors of iNOS activity. These latter agents may become useful tools for studying the role of iNOS in various disease models and may be useful in the therapy of diseases that are associated with an enhanced formation of NO due to iNOS induction, such as inflammation, circulatory shock or cancer." @default.
• W2024401413 created "2016-06-24" @default.
• W2024401413 creator A5005920096 @default.
• W2024401413 creator A5029790590 @default.
• W2024401413 creator A5058049602 @default.
• W2024401413 date "1995-01-01" @default.
• W2024401413 modified "2023-10-18" @default.
• W2024401413 title "Isothioureas: potent inhibitors of nitric oxide synthases with variable isoform selectivity" @default.
• W2024401413 cites W1834041853 @default.
• W2024401413 cites W1929009802 @default.
• W2024401413 cites W1969117625 @default.
• W2024401413 cites W1973758743 @default.
• W2024401413 cites W1979994394 @default.
• W2024401413 cites W1980895604 @default.
• W2024401413 cites W1983187255 @default.
• W2024401413 cites W2001887083 @default.
• W2024401413 cites W2003404259 @default.
• W2024401413 cites W2010707246 @default.
• W2024401413 cites W2011769338 @default.
• W2024401413 cites W2014916185 @default.
• W2024401413 cites W2021117769 @default.
• W2024401413 cites W2022493044 @default.
• W2024401413 cites W2027071001 @default.
• W2024401413 cites W2035988892 @default.
• W2024401413 cites W2040893865 @default.
• W2024401413 cites W2042834418 @default.
• W2024401413 cites W2045846314 @default.
• W2024401413 cites W2048398189 @default.
• W2024401413 cites W2051693516 @default.
• W2024401413 cites W2054345018 @default.
• W2024401413 cites W2064499080 @default.
• W2024401413 cites W2065750772 @default.
• W2024401413 cites W2073713671 @default.
• W2024401413 cites W2075608865 @default.
• W2024401413 cites W2077824574 @default.
• W2024401413 cites W2084398452 @default.
• W2024401413 cites W2114298357 @default.
• W2024401413 cites W2117388675 @default.
• W2024401413 cites W2158686638 @default.
• W2024401413 cites W2158878115 @default.
• W2024401413 cites W2233900733 @default.
• W2024401413 cites W2263438754 @default.
• W2024401413 cites W2320170229 @default.
• W2024401413 cites W2334629896 @default.
• W2024401413 cites W2412065523 @default.
• W2024401413 cites W4234963525 @default.
• W2024401413 cites W72469727 @default.
• W2024401413 doi "https://doi.org/10.1111/j.1476-5381.1995.tb13256.x" @default.
• W2024401413 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1510225" @default.
• W2024401413 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/7533622" @default.
• W2024401413 hasPublicationYear "1995" @default.
• W2024401413 type Work @default.
• W2024401413 sameAs 2024401413 @default.
• W2024401413 citedByCount "261" @default.
• W2024401413 countsByYear W20244014132012 @default.
• W2024401413 countsByYear W20244014132013 @default.
• W2024401413 countsByYear W20244014132014 @default.
• W2024401413 countsByYear W20244014132015 @default.
• W2024401413 countsByYear W20244014132016 @default.
• W2024401413 countsByYear W20244014132017 @default.
• W2024401413 countsByYear W20244014132019 @default.
• W2024401413 countsByYear W20244014132020 @default.
• W2024401413 countsByYear W20244014132021 @default.
• W2024401413 countsByYear W20244014132022 @default.
• W2024401413 countsByYear W20244014132023 @default.
• W2024401413 crossrefType "journal-article" @default.
• W2024401413 hasAuthorship W2024401413A5005920096 @default.
• W2024401413 hasAuthorship W2024401413A5029790590 @default.
• W2024401413 hasAuthorship W2024401413A5058049602 @default.
• W2024401413 hasBestOaLocation W20244014132 @default.
• W2024401413 hasConcept C104264131 @default.
• W2024401413 hasConcept C150903083 @default.
• W2024401413 hasConcept C155647269 @default.
• W2024401413 hasConcept C178790620 @default.
• W2024401413 hasConcept C181199279 @default.
• W2024401413 hasConcept C185592680 @default.
• W2024401413 hasConcept C202751555 @default.
• W2024401413 hasConcept C207001950 @default.
• W2024401413 hasConcept C2777468819 @default.
• W2024401413 hasConcept C2777622882 @default.
• W2024401413 hasConcept C2778326061 @default.
• W2024401413 hasConcept C2779698670 @default.
• W2024401413 hasConcept C515207424 @default.
• W2024401413 hasConcept C519581460 @default.
• W2024401413 hasConcept C55493867 @default.
• W2024401413 hasConcept C71240020 @default.
• W2024401413 hasConcept C86803240 @default.
• W2024401413 hasConcept C98274493 @default.
• W2024401413 hasConceptScore W2024401413C104264131 @default.
• W2024401413 hasConceptScore W2024401413C150903083 @default.
• W2024401413 hasConceptScore W2024401413C155647269 @default.
• W2024401413 hasConceptScore W2024401413C178790620 @default.
• W2024401413 hasConceptScore W2024401413C181199279 @default.
• W2024401413 hasConceptScore W2024401413C185592680 @default.
• W2024401413 hasConceptScore W2024401413C202751555 @default.
• W2024401413 hasConceptScore W2024401413C207001950 @default.
• W2024401413 hasConceptScore W2024401413C2777468819 @default.
• W2024401413 hasConceptScore W2024401413C2777622882 @default.

• next