Synthesis, in vitro evaluation, and molecular docking studies of benzofuran based hydrazone a new inhibitors of urease

Abstract

This work has described the synthesis of novel class (1–25) of benzofuran based hydrazone. The hybrid scaffolds (1–25) of benzofuran based hydrazone were evaluated in vitro, for their urease inhibition. All the newly synthesized analogues (1–25) were found to illustrate moderate to good urease inhibitory profile ranging from 0.20 ± 0.01 to 36.20 ± 0.70 µM. Among the series, compounds 22 (IC50 = 0.20 ± 0.01 µM), 5 (IC50 = 0.90 ± 0.01 µM), 23 (IC50 = 1.10 ± 0.01 µM) and 25 (IC50 = 1.60 ± 0.01 µM) were found to be the many folds more potent than thiourea as standard inhibitor (IC50 = 21.86 ± 0.40 µM). The elevated inhibitory profile of these analogues might be due to presence of dihydroxy and flouro groups at different position of phenyl ring B attached to hydrazone skeleton. These dihydroxy and fluoro groups bearing compounds have shown many folds better inhibitory profile through involvement of oxygen of dihydroxy groups in hydrogen bonding with active site of enzymes. Various types of spectroscopic techniques such as 1H-, 13C- NMR and HREI-MS spectroscopy were used to confirm the structure of all the newly developed compounds. To find SAR, molecular docking studies were performed to understand, the binding mode of potent inhibitors with active site of enzymes and results supported the experimental data.

Keywords

• Synthesis
• Urease
• Benzofuran
• Hydrazone
• Structure activity relationship
• Molecular docking