Abstract: As part of a project aimed at identifying effective low molecular weight nonphosphorus monoanionic inhibitors of PTPs, we have synthesized 4-[(5-arylidene-4-oxo-2-phenyliminothiazolidin-3-yl)methyl]benzoic acids (4) and evaluated their inhibitory activity against human PTP1B and LMW-PTP enzymes. The introduction of a 2-henylimino moiety onto the 4-thiazolidinone ring was designed to enhance the inhibitor/enzyme affinity by means of further favourable interactions with residues of the active site and the surrounding loops. Some of the compounds (4a-d, f) showed interesting inhibition levels in the low micromolar range. The 5-arylidene moiety of acids 4 proved to markedly influence the potency of these inhibitors. Molecular modeling experiments inside the binding sites of both enzymes were performed.

5-Arylidene-2phenylimino-4-thiazolidinones as PTP1B and LMW-PTP inhibitors / R. Ottanà; R. Maccari; R. Ciurleo; P. Paoli; M. Jacomelli; G. Manao; G. Camici; C. Laggner; T. Langer. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 1464-3391. - STAMPA. - 17:(2009), pp. 1928-1937. [10.1016/j.bmc.2009.01.044]

5-Arylidene-2phenylimino-4-thiazolidinones as PTP1B and LMW-PTP inhibitors

PAOLI, PAOLO;MANAO, GIAMPAOLO;CAMICI, GUIDO;
2009

Abstract

Abstract: As part of a project aimed at identifying effective low molecular weight nonphosphorus monoanionic inhibitors of PTPs, we have synthesized 4-[(5-arylidene-4-oxo-2-phenyliminothiazolidin-3-yl)methyl]benzoic acids (4) and evaluated their inhibitory activity against human PTP1B and LMW-PTP enzymes. The introduction of a 2-henylimino moiety onto the 4-thiazolidinone ring was designed to enhance the inhibitor/enzyme affinity by means of further favourable interactions with residues of the active site and the surrounding loops. Some of the compounds (4a-d, f) showed interesting inhibition levels in the low micromolar range. The 5-arylidene moiety of acids 4 proved to markedly influence the potency of these inhibitors. Molecular modeling experiments inside the binding sites of both enzymes were performed.
17
1928
1937
R. Ottanà; R. Maccari; R. Ciurleo; P. Paoli; M. Jacomelli; G. Manao; G. Camici; C. Laggner; T. Langer
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/348778
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