title: Studies on the inhibitory effects of analogues of dapsone on neutrophil function in-vitro.
abstract: We have compared twelve sulphone analogues of dapsone in terms of inhibition both of zymosan-mediated human neutrophil respiratory burst and inhibition of interleukin-1-stimulated neutrophil adhesion to transformed human umbilical vein endothelial cells. Overall, there was a good correlation between the respective rank orders of compound potency in the two test systems. The most effective compounds in terms of respiratory burst and adherence inhibition were the 2-nitro-4-amino-, 2-hydroxy-4-aminopropyl-, and 2-methoxy-4-aminoethyl- derivatives. In general, potency was inversely associated with lipophilicity; compounds with bulky side-chains, e.g. the 2-methyl-4-aminopentyl, 2-methyl-4-aminohexyl and the 2-hydroxymethyl-4-aminoethyl derivatives, were less potent. A 2-hydroxy-4-amino- derivative was the exception, however, with low lipophilicity and relatively low potency. All of the compounds tested showed comparable or greater inhibition in both the neutrophil-mediated assays compared with dapsone. Some of the compounds might, because of their good tissue penetration and lower toxicity than dapsone, have the potential to undergo further development.
authors.affiliation: Department of Pharmaceutical Sciences, Aston University, Aston Triangle, Birmingham, Germany.
authors.forename: M D
authors.initials: MD
authors.lastname: Coleman
authors.forename: J K
authors.initials: JK
authors.lastname: Smith
authors.forename: A D
authors.initials: AD
authors.lastname: Perris
authors.forename: N S
authors.initials: NS
authors.lastname: Buck
authors.forename: J K
authors.initials: JK
authors.lastname: Seydel
mesh_terms: D000328:Adult; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D003622:Dapsone / Q000031:analogs & derivatives / Q000494:pharmacology*; D003874:Dermatitis Herpetiformis / Q000188:drug therapy; D006168:Guinea Pigs; D006801:Humans; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D016897:Respiratory Burst / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D003622:Dapsone