Partial syntheses of aromatic amides: their anti-urease potential and docking studies.

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.

Zenkeramide: a new iso-benzofuranone propanamide and urease inhibitory constituents of Celtis zenkeri Engl stem bark (Ulmaceae).

A new iso-benzofuranone propanamide: 3-(3-oxo-1, 3-dihydroisobenzofuran-1-yl) propanamide (zenkeramide) (1) along with three known compounds: Trans-N-coumaroyltyramine (2), ß-Sitosterol (3) and ß-sitosterol-3-0-ß-D-glucopyranoside (4) were isolated from the ethyl acetate fraction of the stem-bark of Celtis zenkeri Engl (Ulmaceae). The structure of the new compound was elucidated by extensive spectroscopic analysis. The compounds were examined for Urease Inhibitory Activity. Compounds 1 and 2 showed moderate activities (IC50 values (µM) of 42.3 ± 0.19 and 45.2 ± 0.55, respectively), while compounds 3 and 4 were potent inhibitors of the Jack bean urease (IC50 values (µM) of 20.3 ± 0.37and 27.6 ± 0.52, respectively), when compared to the standard inhibitor (thiourea- IC50 21.5 ± 0.47). The isolation of all the compounds from C. zenkeri and the urease activity of compounds 1 and 2 are reported for the first time.