Synthesis, in vitro β-glucuronidase inhibitory activity and in silico studies of novel (E)-4-Aryl-2-(2-(pyren-1-ylmethylene)hydrazinyl)thiazoles.

Abstract Current research is based on the synthesis of novel ( E )-4-aryl-2-(2-(pyren-1-ylmethylene)hydrazinyl)thiazole derivatives ( 3 – 15 ) by adopting two steps route. First step was the condensation between the pyrene-1-carbaldehyde ( 1 ) with the thiosemicarbazide to afford pyrene-1-thiosemicarbazone intermediate ( 2 ). While in second step, cyclization between the intermediate ( 2 ) and phenacyl bromide derivatives or 2-bromo ethyl acetate was carried out. Synthetic derivatives were structurally characterized by spectroscopic techniques such as EI-MS, 1 H NMR and 13 C NMR. Stereochemistry of the iminic double bond was confirmed by NOESY analysis. All pure compounds 2 – 15 were subjected for in vitro β -glucuronidase inhibitory activity. All molecules were exhibited excellent inhibition in the range of IC 50  = 3.10 ± 0.10–40.10 ± 0.90 μM and found to be even more potent than the standard d -saccharic acid 1,4-lactone (IC 50  = 48.38 ± 1.05 μM). Molecular docking studies were carried out to verify the structure-activity relationship. A good correlation was perceived between the docking study and biological evaluation of active compounds.