Synthesis and biological evaluation of nimesulide based new class of triazole derivatives as potential PDE4B inhibitors against cancer cells

[摘要] A new class of 1,2,3-triazol derivatives derived from nimesulide was designed as potential inhibitors of PDE4B. Synthesis of these compounds was carried out via a multi-step sequence consisting of copper-catalyzed azide-alkyne cycloaddition (CuAAC) as a key step in aqueous media. The required azide was prepared via the reaction of aryl amine (obtained from nimesulide) with alpha-chloroacetyl chloride followed by displacing the alpha-chloro group by an azide. Some of the synthesized compounds showed encouraging PDE4B inhibitory properties in vitro that is >50% inhibition at 30 mu M that were supported by the docking studies of these compounds at the active site of PDE4B enzyme (dock scores similar to 28.6 for a representative compound). Two of these PDE4 inhibitors showed promising cytotoxic properties against HCT-15 human colon cancer cells in vitro with IC50 similar to 21-22 mu g/mL. (C) 2013 Elsevier Ltd. All rights reserved.

[发布日期] 2013-12-15

[关键词] Nimesulide;1,2,3-Triazole;Cycloaddition;PDE4B;Cytotoxic activities