Acivicin analogues with an increased affinity for CTP synthetase (CTPS) were designed as potential new trypanocidal agents. The inhibitory activity against CTPS can be improved by increasing molecular complexity, by inserting groups able to establish additional interactions with the binding pocket of the enzyme. This strategy has been pursued with the synthesis of α-amino-substituted analogues of Acivicin and N1-substituted pyrazoline derivatives. In general, there is direct correlation between the enzymatic activity and the invitro anti-trypanosomal efficacy of the derivatives studied here. However, this cannot be taken as a general rule, as other important factors may play a role, notably the ability of uptake/diffusion of the molecules into the trypanosomes.
Synthesis and Biological Evaluation of CTP Synthetase Inhibitors as Potential Agents for the Treatment of African Trypanosomiasis / L. Tamborini, A. Pinto, T.K. Smith, L.L. Major, M.C. Iannuzzi, S. Cosconati, L. Marinelli, E. Novellino, L. Lo Presti, P.E. Wong, M.P. Barrett,C. De Micheli, P. Conti. - In: CHEMMEDCHEM. - ISSN 1860-7179. - 7:9(2012), pp. 1623-1634.
|Titolo:||Synthesis and Biological Evaluation of CTP Synthetase Inhibitors as Potential Agents for the Treatment of African Trypanosomiasis|
TAMBORINI, LUCIA (Primo)
PINTO, ANDREA (Secondo)
DE MICHELI, CARLO (Penultimo)
CONTI, PAOLA (Ultimo)
|Parole Chiave:||Amino acids; CTP synthetase; Isoxazolines; Pyrazolines; Trypanosoma|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
|Data di pubblicazione:||2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/cmdc.201200304|
|Appare nelle tipologie:||01 - Articolo su periodico|