Novel trans -caffeate hydrazide derivatives: synthesis, inhibition of nitric oxide (NO) production and molecular docking studies.

Eight new caffeyl hydrazide derivatives ( 4a-4h ) were synthesised via a convenient esterification of caffeic acid with some substituted aryl acid hydrazides. The synthesised caffeyl derivatives were evaluated for their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages. The fluorobenzoylhydrazide derivatives 4f , 4 g and 4h were found to be the most powerful anti-inflammatory compounds with IC 50 values ranging from 11.90 to 24.17 μM, which were more potent than the reference compound L-NMMA (IC 50 32.8 μM). Additionally, synthesised compounds have been rationalised by using molecular docking studies which were performed in order to understand insights on the action mechanism of newly synthesised inhibitors against inflammatory mediator (iNOS). Obtained data indicate that compounds 4f, 4h , 4a and 4 g were observed to effectively bind to iNOS receptor with dock score values of -11.62, -10.81, -10.78 and -10.51 kcal/mol, respectively.