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Full-Text Articles in Medicinal and Pharmaceutical Chemistry
Antitrypanosomal, Antileishmanial, And Antimalarial Activities Of Quaternary Arylalkylammonium 2-Amino-4-Chlorophenyl Phenyl Sulfides, A New Class Of Trypanothione Reductase Inhibitor, And Of N-Acyl Derivatives Of 2-Amino-4-Chlorophenyl Phenyl Sulfide, Seheli Parveen, M. O. Faruk Khan, Susan E. Austin, Simon L. Croft, Vanessa Yardley, Peter Rock, Kenneth T. Douglas
Antitrypanosomal, Antileishmanial, And Antimalarial Activities Of Quaternary Arylalkylammonium 2-Amino-4-Chlorophenyl Phenyl Sulfides, A New Class Of Trypanothione Reductase Inhibitor, And Of N-Acyl Derivatives Of 2-Amino-4-Chlorophenyl Phenyl Sulfide, Seheli Parveen, M. O. Faruk Khan, Susan E. Austin, Simon L. Croft, Vanessa Yardley, Peter Rock, Kenneth T. Douglas
Pharmaceutical Science and Research
Quaternization of the nitrogen atom of 2-amino-4-chlorophenyl phenyl sulfide analogues of chlorpromazine improved inhibition ∼40-fold (3′,4′-dichlorobenzyl-[5-chloro-2-phenylsulfan- ylphenylamino)-propyl]-dimethylammonium chloride inhibited trypanothione reductase from Trypanosoma cruzi with a linear competitive Ki value of 1.7 ( 0.2 µM). Molecular modelling explained docking orientations and energies by: (i) involvement of the Z-site hydrophobic pocket (roughly bounded by F396′, P398′, and L399′), (ii) ionic interactions for the cationic nitrogen with Glu-466′ or -467′. A series of N-acyl-2-amino-4-chlorophenyl sulfides showed mixed inhibition (Ki, Ki′ ) 11.3-42.8 µM). The quaternized analogues of the 2-chlorophenyl phenylsulfides had strong antitrypanosomal and antileishmanial activity in vitro against T. bruceirhodesiense STIB900, …
Toll-Like Receptor-4 Regulation Of Hepatic Cyp3a11 Metabolism In A Mouse Model Of Lps-Induced Cns Inflammation, Kerry B. Goralski, Dalya Abdulla, Christopher J. Sinal, Andre Arsenault, Kenneth W. Renton
Toll-Like Receptor-4 Regulation Of Hepatic Cyp3a11 Metabolism In A Mouse Model Of Lps-Induced Cns Inflammation, Kerry B. Goralski, Dalya Abdulla, Christopher J. Sinal, Andre Arsenault, Kenneth W. Renton
Faculty Publications and Scholarship
Central nervous system (CNS) infection and inflammation severely reduce the capacity of cytochrome P-450 metabolism in the liver. We developed a mouse model to examine the effects of CNS inflammation on hepatic cytochrome P-450 metabolism. FVB, C57BL/6, and C3H/HeouJ mice were given Escherichia coli LPS (2.5 μg) by intracerebroventricular (ICV) injection. The CNS inflammatory response was confirmed by the elevation of TNF-α and/or IL-1β proteins in the brain. In all mouse strains, LPS produced a 60–70% loss in hepatic Cyp3a11 expression and activity compared with saline-injected controls. Adrenalectomy did not prevent the loss in Cyp3a11 expression or activity, thereby precluding …