Exploring biologically active hybrid pharmacophore N-substituted hydrazine-carbothioamides for urease inhibition: In vitro and in silico approach

Urease is potential target for various human's health complications, such as peptic ulcer, gastric cancer and kidney stone formation. The present study was based on synthesis of new hybrid pharmacophore N-substituted hydrazine-carbothioamides as potential urease inhibitors. Presented method gave excellent yield in range of 85–95% for hydrazine-carbothioamides derivatives (3a-s) after reaction of mono- and disubstituted hydrazides (1a-k) and substituted isothiocyanates (2a-d). All newly derivatives were characterized by advanced spectroscopic techniques (FTIR, 1HNMR, 13CNMR, EMS) and were assessed for their urease inhibition potential. All analogs except for 3k, 3l and 3m demonstrated strong inhibitory potential for urease with IC50 values of 8.45 ± 0.14 to 25.72 ± 0.23 μM as compared to standard thiourea (IC50 21.26 ± 0.35 μM). The structure-activity relationship and mode of interaction was established by molecular docking studies. It was revealed that the N-substituted hydrazine-carbothioamides interacted with nickel atoms present in the active site of urease and supported the correlations with the experimental findings. Therefore, the afforded hydrazine-carbothioamides derivatives are interesting hits for urease inhibition studies with future prospects of modification and optimization.