Synthesis, crystal structure, molecular docking studies and bio-evaluation of some N4-benzyl-substituted isatin-3-thiosemicarbazones as urease and glycation inhibitors

Abstract

Fifteen N4-benzyl-substituted isatin-3-thiosemicarbazones 5a-o were synthesized and evaluated for their urease and glycation inhibitory potential. Lemna aequinocitalis growth and Artemia salina assays were also done to determine their phytotoxic and toxic effects. All compounds are potent inhibitors of the urease enzyme, displaying inhibition [half maximal inhibitory concentration (IC50)=1.08±0.12-11.23±0.19 μm] superior to that of the reference inhibitor thiourea (IC50=22.3±1.12 μm). Compounds 5c, 5d, 5h, 5j,k are potent antiglycating agents, showing glycation inhibitory activity better than that of the reference inhibitor rutin (IC50 values 209.87±0.37-231.70±6.71 vs. 294.5±1.5 μm). In the phytotoxicity assay, 11 thiosemicarbazones 5a-d, 5g, 5h, 5j-l, 5n,o are active, demonstrating 5-100% growth inhibition of L. aequinocitalis at the highest tested concentrations (1000 or 500 μg/mL). In the brine shrimp (A. salina) lethality bioassay, three derivatives 5b, 5j and 5o are active with median lethal dose (LD50) values of 3.63×10-5, 2.90×10-5 and 2.31×10-4 m, respectively.