Synthesis and biological evaluation of 3-benzyl-1-methyl- and 1-methyl-3-phenyl-isothioureas as potential inhibitors of iNOS

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 3, 2005, Pages 539-543

  Paesano, Nicola ^a   Marzocco, Stefania ^a   Vicidomini, Caterina ^a   Saturnino, Carmela ^a   Autore, Giuseppina ^a   De Martino, Giovanni ^a   Sbardella, Gianluca ^a  

^a UNIVERSITY OF SALERNO   (Italy)

Author keywords

iNOS; Isothioureas; Nitric oxide

Indexed keywords

1 METHYL 3 PHENYLISOTHIOUREA; 3 BENZYL 1 METHYLISOTHIOUREA; LIPOPOLYSACCHARIDE; NITRIC OXIDE SYNTHASE INHIBITOR; PSEUDOTHIOUREA DERIVATIVE; THIOUREA DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CELL LINE; CONTROLLED STUDY; DRUG SYNTHESIS; EVALUATION; MACROPHAGE; MOUSE; NONHUMAN;

ANIMALS; CELL LINE; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; LIPOPOLYSACCHARIDES; MACROPHAGES; MICE; NITRIC OXIDE SYNTHASE; NITRIC OXIDE SYNTHASE TYPE II; STRUCTURE-ACTIVITY RELATIONSHIP; THIOUREA;

EID: 12444284865     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.11.047     Document Type: Article

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25. Abstract available
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27. The iNOS inhibitory activity of compounds 4-8 was determined (for more details see S. Marzocco, S. Piacente, C. Pizza, W. Oleszek, A. Stochmal, A. Pinto, R. Sorrentino, and G. Autore Life Sci. 75 2004 1491 1501) by measuring nitric oxide release in medium in the presence of each compound. In particular, nitrite accumulation, an indicator of NO release, was detected by Griess reaction (
28. 3 u/ml) challenge. Briefly, 100 μl of cell culture medium were mixed with 100 μl of Griess reagent (equal volumes of 1% (w/v) sulfanilamide in 5% (v/v) phosphoric acid 0.1% (w/v) naphthylethylendiamine-HCl) and incubated at room temperature for 10 min, and then the absorbance at 550 nm was measured in a Titertek microplate reader (DASIT). Fresh culture medium was used as blank in all the experiments. The amount of nitrite in the samples was calculated from a sodium nitrite standard curve freshly prepared in culture medium. Results are expressed as percentage of inhibition calculated versus cells treated only with LPS
29. -6 M more reliable