title: Synthesis and biological evaluation of penam sulfones as inhibitors of beta-lactamases.
abstract: The chemical synthesis of a series of new penam sulfone derivatives bearing a 2beta-substituted-oxyimino and -hydrazone substituents, their beta-lactamase inhibitory properties against selected enzymes representing class A and C beta-lactamases are reported. The oxime containing penam sulfones strongly inhibited the Escherichia coli TEM-1 and Klebsiella pneumoniae cefotaximase (CTX-1) enzymes, but moderately inhibited the Pseudomonas aeruginosa 46012 cephalosporinase; while the 2beta-substituted-hydrazone derivatives were generally less active against these enzymes. Furthermore, most of the inhibitors enhanced the antibacterial activities of piperacillin (PIP) and ceftazidime (CAZ) particularly against TEM-1 and CTX-1 producing bacterial strains.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, PO Box 24923, Safat 13110, Kuwait. dphillips@hsc.edu.kw
authors.forename: Oludotun A
authors.initials: OA
authors.lastname: Phillips
authors.forename: Andhe V N
authors.initials: AV
authors.lastname: Reddy
authors.forename: Eduardo L
authors.initials: EL
authors.lastname: Setti
authors.forename: Paul
authors.initials: P
authors.lastname: Spevak
authors.forename: David P
authors.initials: DP
authors.lastname: Czajkowski
authors.forename: Herninder
authors.initials: H
authors.lastname: Atwal
authors.forename: Sameeh
authors.initials: S
authors.lastname: Salama
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Micetich
authors.forename: Samarendra N
authors.initials: SN
authors.lastname: Maiti
mesh_terms: D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D007711:Klebsiella pneumoniae / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D011550:Pseudomonas aeruginosa / Q000201:enzymology; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D013450:Sulfones; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases