Imidazo[4,5-a]acridines and Pyrazolo[4,3-a]acridines as a New Class of Urease Inhibitors: Synthesis, In Vitro Interactions, and Molecular Docking Studies

Abstract

Despite the important role that urease plays in the global nitrogen cycle, inhibition of its activity is demanded owing to the development of diseases such as stomach ulcers and some cancers. In the search for a potent urease inhibitor, imidazoacridine and pyrazoloacridine derivatives were synthesized and evaluated for their urease inhibitory potential. The desired compounds were obtained in two steps at high yields in basic media. Title compounds exhibited a variable degree of inhibitory interaction potential having IC₅₀ values ranging between 14.83 ± 0.03 and 22.21 ± 0.6 μM compared with standard thiourea. To understand the binding interaction of most active analogs with ab active site of urease enzyme, molecular modeling of the complexes (ligand–enzyme) was also performed.