- Microwave-assisted synthesis of 4-quinolylhydrazines followed by nickel boride reduction: a convenient approach to 4-aminoquinolines and derivatives
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Nickel(II) chloride/sodium borohydride combination was employed for the reduction of 4-hydrazinoquinoline derivatives to the corresponding anilines. This reductive protocol was efficiently applied for the reductive cleavage of monosubstituted hydrazines. We described herein the microwave-assisted synthesis of 4-hydrazinoquinolines, which furnished a high yielding and rapid two-step procedure for the synthesis, under mild conditions, of 4-aminoquinolines as antimalarial precursors.
- Gemma, Sandra,Kukreja, Gagan,Tripaldi, Pierangela,Altarelli, Maria,Bernetti, Matteo,Franceschini, Silvia,Savini, Luisa,Campiani, Giuseppe,Fattorusso, Caterina,Butini, Stefania
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p. 2074 - 2077
(2008/09/18)
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- Inhibition of Trypanosoma cruzi trypanothione reductase by acridines: Kinetic studies and structure-activity relationships
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Series of 9-amino and 9-thioacridines have been synthesized and studied as inhibitors of trypanothione reductase (TR) from Trypanosoma cruzi, the causative agent of Chagas' disease. The compounds are structural analogues of the acridine drug mepacrine (quinacrine), which is a competitive inhibitor of the parasite enzyme, but not of human glutathione reductase, the closest related host enzyme. The 9-aminoacridines yielded apparent K(i) values for competitive inhibition between 5 and 43 μM. The most effective inhibitors were those with the methoxy and chlorine substituents of mepacrine and NH2 or NHCH(CH3)(CH2)4N(Et)2 at C9. Detailed kinetic analyses revealed that in the case of 9- aminoacridines more than one inhibitor molecule can bind to the enzyme. In contrast, the 9-thioacridine derivatives inhibit TR with mixed-type kinetics. The kinetic data are discussed in light of the three-dimensional structure of the TR-mepacrine complex. The conclusion that structurally very similar acridine compounds can give rise to completely different inhibition patterns renders modelling studies and quantitative structure-activity relationships difficult.
- Bonse, Susanne,Santelli-Rouvier, Christiane,Barbe, Jacques,Krauth-Siegel, R. Luise
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p. 5448 - 5454
(2007/10/03)
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