Synthesis, Evaluation and Mechanism Exploration of 2-(N-(3-nitrophenyl)-n-phenylsulfonyl)aminoacetohydroxamic Acids As Novel Urease Inhibitors.

Thirteen 2-(N-(3-nitrophenyl)-N-phenylsulfonyl)aminoacetohydroxamic acids which were reported for the first time were designed and synthesized as novel urease inhibitors. Most of them showed higher potency than the positive control acetohydroxamic acid, with 2-(N-(3-nitrophenyl)-N-(4-bromophenylsulfonyl)amino-acetohydroxamic acid (d7) being the most active (IC50 = 0.13 +/- 0.01 mu M). Compound d7 reversibly inhibits urease with mixed mechanism showing excellent binding affinity to urease active site (KD = 0.34 nM, Ki=0.065 +/- 0.003 mu M andK ' i = 1.20 +/- 0.09 mu M) and very low cytotoxicity against mammalian cells (cell viability of 91.4 % against HepG2 at 250 mu g/mL). These positive results indicated that d7 may be used as the lead for further research to develop urease inhibitors with promising properties.