1-[(4'-Chlorophenyl) carbonyl-4-(aryl) thiosemicarbazide derivatives as potent urease inhibitors: Synthesis, in vitro and in silico studies.

A series of 1-[(4'-chlorophenyl)carbonyl-4-(aryl)thiosemicarbazide derivatives 1-25 was synthesized and characterized by spectroscopic techniques such as EI-MS and ¹ H NMR. All compounds were screened for urease inhibitory activity in vitro and demonstrated excellent inhibitory activity in the range of IC ₅₀  = 0.32 ± 0.01-25.13 ± 0.13 μM as compared to the standard thiourea (IC ₅₀  = 21.25 ± 0.13 μM). Amongst the potent analogs, compounds 3 (IC ₅₀  = 2.31 ± 0.01 μM), 6 (IC ₅₀  = 2.14 ± 0.04 μM), 10 (IC ₅₀  = 1.14 ± 0.06 μM), 20 (IC ₅₀  = 2.15 ± 0.05 μM), and 25 (IC ₅₀  = 0.32 ± 0.01 μM) are many folds more active than the standard. Structure-activity relationship (SAR) was rationalized by looking at the effect of diversely substituted aryl ring on inhibitory potential which predicted that regardless of the nature of substituents, their positions on aryl ring is worth important for the potent activity. Furthermore, to verify these interpretations, in silico study was performed on all compounds and a good correlation was perceived between the biological evaluation and docking study of compounds.
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