Discovery of covalent inhibitors of glyceraldehyde-3-phosphate dehydrogenase, a target for the treatment of malaria
Articolo
Data di Pubblicazione:
2014
Citazione:
Discovery of covalent inhibitors of glyceraldehyde-3-phosphate dehydrogenase, a target for the treatment of malaria / S. Bruno, A. Pinto, G. Paredi, L. Tamborini, C. De Micheli, V. La Pietra, L. Marinelli, E. Novellino, P. Conti, A. Mozzarelli. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 57:17(2014 Sep 11), pp. 7465-7471. [10.1021/jm500747h]
Abstract:
We developed a new class of covalent inhibitors of Plasmodium falciparum glyceraldehyde-3-phosphate dehydrogenase, a validated target for the treatment of malaria, by screening a small library of 3-bromo-isoxazoline derivatives that inactivate the enzyme through a covalent, selective bond to the catalytic cysteine, as demonstrated by mass spectrometry. Substituents on the isoxazolinic ring modulated the potency up to 20-fold, predominantly due to an electrostatic effect, as assessed by computational analysis.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
S. Bruno, A. Pinto, G. Paredi, L. Tamborini, C. De Micheli, V. La Pietra, L. Marinelli, E. Novellino, P. Conti, A. Mozzarelli
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