title: Cysteine based novel noncompetitive inhibitors of urease(s)--distinctive inhibition susceptibility of microbial and plant ureases.
abstract: Based on the catalysis mechanism of urease, a homologous series of 10 cysteine derivatives (CysDs) was designed and synthesized, and their inhibitory activities were evaluated for microbial ureases (Bacillus pasteurii, BPU, and Proteus mirabilis, PMU) and for a plant urease [jack bean (Cavavalia ensiformis), JBU]. As already described, thiol-compounds might inhibit urease activity by chelating the nickel atoms involved in the catalysis process. In contrast to cysteine, which has been reported to be a very weak urease inhibitor, we verified a potential inhibitory activity of these CysDs. The kinetic data demonstrate that thiol derivatives are more effective than the respective thioether derivatives. Besides, thiol-CysDs had a reduced activity in acidic pH (5.0). Lineweaver-Burk plots indicated that the nature of inhibition was of noncompetitive type for all 10 compounds, with the minimum Ki value of 2 microM for N,N-dimethyl L-cysteine. It is proposed that these classes of compounds are more potent inhibitors of the bacterial ureases, compared with the plant-originated urease. Since microbial urease is directly involved in the infection process of many pathological organisms, this work demonstrates that thiol-CysDs represent a class of new potential urease inhibitors.
authors.affiliation: International Center for Chemical Sciences, HEJ Research Institute of Chemistry, University of Karachi, Karachi 75270, Pakistan. zareen_amtul@fulbrightweb.org
authors.forename: Zareen
authors.initials: Z
authors.lastname: Amtul
authors.forename: Naheed
authors.initials: N
authors.lastname: Kausar
authors.forename: Cristian
authors.initials: C
authors.lastname: Follmer
authors.forename: Richard F
authors.initials: RF
authors.lastname: Rozmahel
authors.lastname: Atta-Ur-Rahman
authors.forename: Syed Arif
authors.initials: SA
authors.lastname: Kazmi
authors.forename: Mohammed Saleh
authors.initials: MS
authors.lastname: Shekhani
authors.forename: Jason L
authors.initials: JL
authors.lastname: Eriksen
authors.forename: Khalid M
authors.initials: KM
authors.lastname: Khan
authors.forename: Mohammad Iqbal
authors.initials: MI
authors.lastname: Choudhary
mesh_terms: D001419:Bacteria / Q000187:drug effects / Q000201:enzymology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007887:Fabaceae / Q000187:drug effects / Q000201:enzymology*; D013329:Structure-Activity Relationship; D014510:Urease / Q000037:antagonists & inhibitors*
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D014510:Urease; D003545:Cysteine