Background: Designing drug candidates against the urease enzyme, which has been found
responsible for many pathological disorders in human beings as well as in animals, was done by insilico
Methods: Studies were carried out on a designed library of diosmin derivatives with the help of Schrodinger’s
maestro package of molecular docking software against a crystallographic complex of plant enzyme
Jack bean urease (PDB ID: 3LA4). Best twelve derivatives of diosmin were selected for synthesis
by considering their interaction energy along with docking score and were further investigated for antioxidant,
urease inhibitory and Anti-H. pylori activity by in- vitro method along with ADMET analysis.
Results: In-vitro results of series concluded compounds D2a, D2d and D7 (IC50 12.6 ± 0.002, 14.14 ±
0.001 and 15.64 ± 0.012 µM respectively in urease inhibition and 5.195 ± 0.036, 5.39 ± 0.020 and 5.64±
0.005 µM in antioxidant behavior against DPPH) were found to be significantly potent with excellent
docking score -11.721, -10.795, -10.188 and binding energy -62.674, -63.352, -56.267 kJ/ mol as compared
to standard drugs thiourea and acetohydroxamic acid (-3.459, -3.049 and -21.156 kJ/mol and -
17.454 kJ/mol) whereas compounds D2b, D5b, D5d and D6 were found moderate in urease inhibitory
Conclusion: Selected candidates from the outcome of in-vitro urease inhibitory were further examined
for anti- H. pylori activity by a well diffusion method against H. pylori bacterium (DSM 4867). Compound
D2a showed good anti-H. Pylori activity with a zone of inhibition 10.00 ± 0.00 mm and MIC
value 500µg/mL as compared to standard drug acetohydroxamic acid having a zone of inhibition 9.00 ±
0.50mm and MIC 1000µg/mL. In- silico studies played an important role in designing the potent ligands
against urease protein as well as in explaining the binding pattern of designed and synthesized ligand
within the active pocket of jack bean urease protein. ADMET studies were also carried out to check the
drug similarity of designed compounds by the means of quikprop module of molecular docking software.
Hence, the present investigation studies will provide a new vision for the discovery of potent
agents against H. pylori and urease associated diseases.