The aromatic amide: N-p-trans-coumaroyltyramine (1) was isolated for the first time from the stem bark of Celtis zenkeri (Ulmaceae). Its four new derivatives (1a-d) and previously reported diacetylated product (1e) have been synthesized and characterized spectroscopically followed by their in vitro screening for anti-urease potential. The diacetylated product (1e) was found to be the most potent inhibitor with an IC50 value of 19.5 ± 0.23 μM compared to thiourea used as standard (21.5 ± 0.47 μM). Furthermore, molecular docking studies were conducted revealing striking interactions of the active compounds with catalytically important residues such as His593, Ala636 and Asp633. Subsequently, the prime MM-GBSA calculations provided the ligand binding and strain energies. The molecular dynamic simulations validated the docked and post-docked complexes where compounds 1b, 1c, 1d and 1e remained stable throughout the simulation. This study provides insight into the N-p-trans-coumaroyltyramine derivatives (1b-e) that can block the substrate entry, thereby inhibiting the urease's catalytic activity. Hence, these hit compounds can proceed for further pre-clinical studies for drug discovery against urease.Communicated by Ramaswamy H. Sarma.
Keywords: Celtis zenkeri; N-p-trans-coumaroyltyramine; anti-urease activity; aromatic amide derivatives; molecular docking.