135611-22-2Relevant academic research and scientific papers
3-Mercapto-1,2,4-triazoles and N-acylated thiosemicarbazides as metallo-β-lactamase inhibitors
Faridoon,Hussein, Waleed M.,Vella, Peter,Islam, Nazar Ul,Ollis, David L.,Schenk, Gerhard,McGeary, Ross P.
, p. 380 - 386 (2012/02/04)
The production of β-lactamases is an effective strategy by which pathogenic bacteria can develop resistance against β-lactam antibiotics. While inhibitors of serine-β-lactamases are widely used in combination therapy with β-lactam antibiotics, there are no clinically available inhibitors of metallo-β-lactamases (MBLs), and so there is a need for the development of such inhibitors. This work describes the optimisation of a lead inhibitor previously identified by fragment screening of a compound library. We also report that thiosemicarbazide intermediates in the syntheses of these compounds are also moderately potent inhibitors of the IMP-1 MBL from Pseudomonas aeruginosa. The interactions of these inhibitors with the active site of IMP-1 were examined using in silico methods.
Penicillin inhibitors of purple acid phosphatase
Faridoon,Hussein, Waleed M.,Ul Islam, Nazar,Guddat, Luke W.,Schenk, Gerhard,McGeary, Ross P.
supporting information; experimental part, p. 2555 - 2559 (2012/05/20)
Purple acid phosphatases (PAPs) are binuclear metallohydrolases that have a multitude of biological functions and are found in fungi, bacteria, plants and animals. In mammals, PAP activity is linked with bone resorption and over-expression can lead to bone disorders such as osteoporosis. PAP is therefore an attractive target for the development of drugs to treat this disease. A series of penicillin conjugates, in which 6-aminopenicillanic acid was acylated with aromatic acid chlorides, has been prepared and assayed against pig PAP. The binding mode of most of these conjugates is purely competitive, and some members of this class have potencies comparable to the best PAP inhibitors yet reported. The structurally related penicillin G was shown to be neither an inhibitor nor a substrate for pig PAP. Molecular modelling has been used to examine the binding modes of these compounds in the active site of the enzyme and to rationalise their activities.
Laser Flash Photolysis of tert-Butyl Aroylperbenzoates: Kinetics of the Singlet and Triplet States and the Aroylphenyl Radicals
Shah, Bipin K.,Neckers, Douglas C.
, p. 1830 - 1835 (2007/10/03)
tert-Butyl aroylperbenzoates (1-4) were studied by laser flash photolysis (LFP). LFP (380 nm, pulse width ～350 fs) of 2 and 3 allowed direct observation of their singlet states, which showed broad absorption (λmax ～ 625 nm; τ ～ 20 and ～7.9 ps, respectively). The triplet state of each (λmax ～ 530-560 nm) rapidly dissociates by O-O cleavage as indicated by the short triplet lifetimes (e.g., triplet lifetime of 3 ～0.74 ns). The ～550 nm absorption obtained from the 355 nm LFP (pulse width ～7 ns) of 1, 2, and 4 has been assigned to the corresponding aroylphenyl radicals. Two representative radicals (4-benzoylphenyl 5 and 3-(4′-methylbenzoyl)phenyl 6) investigated in detail showed solvent-dependent lifetimes. Absolute bimolecular rate constants of reactions of these radicals with various quenchers including double-bond-containing monomers have been observed to range from 7.56 × 107 to 1.68 × 109 M-1 s-1 in CCl4 at room temperature. A possible structure of the aroylphenyl radicals and the transition responsible for the 550 nm absorption are discussed.
Synthesis, Crystal Structures, and Laser Flash Photolysis of tert-Butyl Aroylperbenzoates
Shah, Bipin K.,Neckers, Douglas C.
, p. 8368 - 8372 (2007/10/03)
tert-Butyl aroylperbenzoates (1-7) were synthesized. Single-crystal structures for 2 and 5 show that the perester and benzophenone carbonyl groups are almost coplanar in each. Laser flash photolysis (LFP, λex = 355 nm) of 1-5 in CCl4
