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

• Autor(a) principal: Mareddy, Jyoti
• Data de Publicação: 2013
• Outros Autores: Nallapati, Suresh Babu, Anireddy, Jayasree, Devi, Yumnam Priyadarshini, Mangamoori, Lakshmi Narasu, Kapavarapu, Ravikumar, Pal, Sarbani
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10316/27125; https://doi.org/10.1016/j.bmcl.2013.10.035
• topic: Nimesulide; 1,2,3-Triazole; Cycloaddition; PDE4B; Cytotoxic activities

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 α-chloroacetyl chloride followed by displacing the α-chloro group by an azide. Some of the synthesized compounds showed encouraging PDE4B inhibitory properties in vitro that is >50% inhibition at 30 μM that were supported by the docking studies of these compounds at the active site of PDE4B enzyme (dock scores ∼ −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 ∼ 21–22 μg/mL.